59 results on '"Pilotto JH"'
Search Results
2. LB1.63 High acceptance of cervical self-collection for detection of hpv, hhv-2 and hiv-1 in women living in tapajÓs region, amazÓÔnia, brazil
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Rodrigues, LLS, Paula, VS de, Morgado, MG, Oliveira, NS, Lima, LRP, Sahasrabuddhe, V, Nicol, AF, and Pilotto, JH
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IntroductionCervical self-collection is a safe and efficient method for detecting sexually transmitted infections (STIs). The study aims to verify the acceptance of cervical self-collection and the prevalence of HPV, HHV-2 and HIV-1 infection in women living in the TapajÓÔáéáós region, AmazÓÔáéáóônia, Brazil.MethodsCross-sectional study with women attending in SantarÓÔáéáóôém-ParÓÔáéáóôéá. The collection was performed between August 2015 and January 2017. Participants collected cervical scrapings and peripheral blood. Those who accepted, also performed cervical self-collection. Detection of HPV DNA was performed by nestedPCR with MY09/11 and GP5/6+primers and typing was done by sequencing. Detection of HHV-2 DNA was performed by real-time PCR with Taqman. Identification of anti-HIV-1/2 antibodies was made by Alere Determine Kit.ResultsA total of 206 specimens were obtained from 112 women. The acceptance of cervical self-collection was 84% (94/112) and HPV DNA was identified in 39.4% (37/94) of the samples. While the prevalence of HPV infection in cervical scraping was 32.1% (36/112). All the women presented Papanicolaou negative for malignancy. The most prevalent types were HPV-16 and HPV-18. The overall prevalence of HHV-2 infection was 8.9%. The concordance rate in the molecular diagnosis between cervical scraping and cervical self-collection was 65% (26/40) for HPV and 50% (4/8) for HHV-2. No woman had HIV-1 reactive serology.ConclusionA high prevalence of HPV infection was found in women without dysplastic lesion. Cervical self-collection had high acceptance, moderate concordance rate in the detection of HPV DNA compared to cervical scraping, and alone it was more efficient in the detection of HPV. This is the first study in women living in TapajÓÔáéáóôéáós region and the findings strongly suggest that cervical self-collection may be a useful tool for increasing access to diagnosis of STIs and screening for cervical cancer in women living in the Amazon.
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- 2017
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3. The impact of early anti-SARS-CoV-2 antibody production on the length of hospitalization stay among COVID-19 patients.
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de Almeida DV, Cezar PA, Fernandes TFB, Schwarz MGA, Mendonça-Lima L, Giacoia-Gripp CBW, Côrtes FH, Lindenmeyer Guimarães M, Pilotto JH, De Sá NBR, Cazote AdS, Gomes LR, Quintana MdSB, Ribeiro-Alves M, Coelho LE, Geraldo KM, Ribeiro MPD, Cardoso SW, Grinsztejn B, Veloso V, and Morgado MG
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- Humans, Antibody Formation, SARS-CoV-2, Antibodies, Viral, Antibodies, Neutralizing, Hospitalization, COVID-19
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Importance: The study provides valuable insights into the sociodemographic characteristics, clinical outcomes, and humoral immune response of those affected by the virus that has devastated every field of human life since 2019; the COVID-19 patients. Firstly, the association among clinical manifestations, comorbidities, and the production of neutralizing antibodies (Nabs) against SARS-CoV-2 is explored. Secondly, varying levels of Nabs among patients are revealed, and a significant correlation between the presence of Nabs and a shorter duration of hospitalization is identified, which highlights the potential role of Nabs in predicting clinical outcomes. Lastly, a follow-up conducted 7 months later demonstrates the progression and persistence of Nabs production in recovered unvaccinated individuals. The study contributes essential knowledge regarding the characteristics of the study population, the early humoral immune response, and the dynamics of Nabs production over time. These findings have significant implications for understanding the immune response to COVID-19 and informing clinical management approaches., Competing Interests: The authors declare no conflict of interest.
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- 2023
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4. Virologic response to antiretroviral therapy in people with HIV and tuberculosis in high tuberculosis burden countries.
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De Castro N, Chazallon C, Brites C, Messou E, Khosa C, Laureillard D, Chau GD, Pilotto JH, Eholié S, Delaugerre C, Molina JM, Wittkop L, Grinsztejn B, and Marcy O
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- Humans, Raltegravir Potassium therapeutic use, RNA, Viral, Viral Load, HIV Infections complications, Tuberculosis drug therapy, Tuberculosis complications, Anti-HIV Agents therapeutic use
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Objective: We sought to compare virologic outcomes on antiretroviral therapy (ART) between people with HIV (PWH) also treated for tuberculosis in the different countries who participated to two randomized trials., Design: Pooled analysis of two randomized clinical trials., Methods: In the phase II Reflate TB and phase III Reflate TB2 trials conducted in Brazil, Côte d'Ivoire, Mozambique and Vietnam, ART-naïve PWH treated for tuberculosis were randomized to receive raltegravir or efavirenz. We assessed country differences in baseline characteristic using Wilcoxon tests and chi-square, or Fisher's exact test. We used logistic regression to analyze determinants of virologic success, defined as week-48 plasma HIV-1 RNA <50 copies/ml., Results: Of 550 participants (140 from Brazil, 170 from Côte d'Ivoire, 129 from Mozambique and 111 from Vietnam) with median baseline HIV-1 RNA of 5.4 log 10 copies/ml, 362 (65.8%) achieved virologic success at week 48. Virologic success rates were: 105/140 (75.0%) in Brazil, 99/170 (58.2%) in Côte d'Ivoire, 84/129 (65.1%) in Mozambique and 74/111 (66.7%) in Vietnam ( P = 0.0233). Baseline HIV-1 RNA, but not the country, was independently associated with virologic success: baseline HIV-1 RNA ≥500 000 copies/ml (reference), HIV RNA <100 000 copies/ml odds ratio 3.12 [95% confidence interval (CI) 1.94; 5.01] and HIV-1 RNA 100 000-499 999 copies/ml odds ratio: 1.80 (95% CI 1.19; 2.73). Overall, 177/277 (63.9%) patients treated with raltegravir and 185/273 (67.9%) patients treated with efavirenz had a plasma HIV-1 RNA <50 copies/ml at week 48., Conclusions: Virologic response to antiretroviral therapy in PWH with TB varied across countries but was mainly driven by levels of pretreatment HIV-1 RNA., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2023
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5. Diversity of Anal HPV and Non-HPV Sexually Transmitted Infections and Concordance with Genital Infections in HIV-Infected and HIV-Uninfected Women in the Tapajós Region, Amazon, Brazil.
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Rodrigues LLS, Pilotto JH, Martinelli KG, Nicol AF, De Paula VS, Gheit T, Oliveira NSC, Silva-de-Jesus C, Sahasrabuddhe VV, Da Silva DM, Kast WM, Hardick J, Gaydos CA, and Morgado MG
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- Humans, Female, Brazil epidemiology, Cross-Sectional Studies, Chlamydia trachomatis, Cervix Uteri, Neisseria gonorrhoeae, Prevalence, Papillomavirus Infections complications, Papillomavirus Infections epidemiology, Sexually Transmitted Diseases complications, Sexually Transmitted Diseases epidemiology, HIV Infections complications, HIV Infections epidemiology, Chlamydia Infections complications, Chlamydia Infections epidemiology
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The aim of this study was to classify the diversity of anal HPV and non-HPV sexually transmitted infections (STIs) and compare the concordance between anal and genital infections in HIV-infected and uninfected women living in the Tapajós region, Amazon, Brazil. A cross-sectional study was performed with 112 HIV-uninfected and 41 HIV-infected nonindigenous women. Anal and cervical scrapings were collected and analyzed for HPV, Chlamydia trachomatis (CT) , Neisseria gonorrheae (NG), Trichomonas vaginalis (TV), Mycoplasma genitalium (MG), and Human alphaherpesvirus 2 (HSV-2). The Kappa test evaluated the concordance between anal and genital infections. The overall prevalence of anal HPV infection was 31.3% in HIV-uninfected and 97.6% in HIV-infected women. The most frequent anal high-risk HPV (hrHPV) types were HPV18 and HPV16 in HIV-uninfected women and HPV51, HPV59, HPV31, and HPV58 in HIV-infected women. Anal HPV75 Betapapillomavirus was also identified. Anal non-HPV STIs were identified in 13.0% of all participants. The concordance analysis was fair for CT, MG, and HSV-2, almost perfect agreement for NG, moderate for HPV, and variable for the most frequent anal hrHPV types. Thus, a high prevalence of anal HPV infection with moderate and fair concordance between anal and genital HPV and non-HPV STIs was observed in our study.
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- 2023
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6. Effects of Initiating Raltegravir-Based Versus Efavirenz-Based Antiretroviral Regimens During Pregnancy on Weight Changes and Perinatal Outcomes: NICHD P1081.
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Coutinho CM, Warshaw MG, Duarte G, Stek A, Violari A, Hofer CB, Deville JG, Ngocho JS, Pilotto JH, Correa MD Jr, Shapiro DE, Fuller TL, Chakhtoura N, Mirochnick M, and João EC
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- Female, Pregnancy, Humans, United States, Raltegravir Potassium therapeutic use, Integrase Inhibitors, Weight Gain, National Institute of Child Health and Human Development (U.S.), HIV Infections drug therapy
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Background: Integrase inhibitors have been associated with excess gestational weight gain that may lead to adverse pregnancy outcomes (APOs). This post hoc analysis of NICHD P1081 compared antepartum changes in weight and body mass index (BMI) in pregnant women initiating raltegravir- or efavirenz-based combined antiretroviral therapy (cART) and examined associations between rates of weight gain and APOs., Setting: NICHD P1081 enrolled antiretroviral-naive pregnant women living with HIV in the second and third trimester in Brazil, Tanzania, South Africa, Thailand, Argentina, and the United States., Methods: Two hundred eighty-one women enrolled between 20 and 31 gestational weeks were randomized to raltegravir- or efavirenz-based cART and followed for ≥4 weeks. A low rate of weight gain was defined as <0.18 kg/wk and high as >0.59 kg/wk. We compared weight gain and BMI increase between treatment arms using Kruskal-Wallis tests. Logistic regression was used to investigate the association between weight gain and APOs., Results: Raltegravir-based cART was associated with significantly higher antepartum weight gain (median 0.36 kg/wk versus 0.29 kg/wk, P = 0.01) and BMI increase (median 0.14 kg/m 2 /wk versus 0.11 kg/m 2 /wk, P = 0.01) compared with efavirenz-based treatment. Women on raltegravir had less low weight gain (18% versus 36%) and more high weight gain (21% versus 12%) ( P = 0.001). Women with low weight gain were more likely than those with normal weight gain to have small for gestational age infants or a composite of APOs., Conclusions: A raltegravir-based antiretroviral regimen was associated with significantly higher antepartum rate of weight gain and BMI increase compared with efavirenz-based treatment in antiretroviral-naive pregnant women., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2022
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7. Sustained Virologic Suppression Reduces HIV-1 DNA Proviral Levels and HIV Antibodies in Perinatally HIV-Infected Children Followed from Birth.
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Fuller T, Kerin T, Cortado R, Benamor Teixeira ML, Fragoso da Silveira Gouvêa MI, Moreira C, Santos Cruz ML, Pilotto JH, Gomes I, Santos B, Rocha T, Soni PR, Joao E, Shin-Sim M, Bryson Y, and Nielsen-Saines K
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- Child, Humans, Infant, Proviruses genetics, HIV Antibodies, Viral Load, DNA, Viral analysis, RNA, HIV-1 genetics, HIV Infections drug therapy
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The extent to which perinatally HIV-infected children, following cART initiation, develop a low proviral reservoir burden over time, as measured by HIV DNA droplet-digital polymerase chain reaction (ddPCR) and the effect on HIV antibody is not well characterized. We measured proviral HIV DNA and plasma RNA virus load (VL) in 37 perinatally HIV-infected children at 6 months of age who initiated stable cART. At 6-11 years of age, HIV proviral DNA, HIV VL (RNA), and HIV antibody by Western Blot (WB) were assessed. CART was initiated before 6 months of age in 13 children and after 6 months in 24. At school age, the HIV DNA levels did not differ by the timing of cART, and the HIV DNA levels were lower in children with negative/indeterminate WB ( p = 0.0256). Children with undetectable HIV RNA VL > 50% of the time since cART initiation had lower median DNA VL than children with undetectable VL < 50% of the time ( p = 0.07). Long-term viral suppression in perinatally HIV-infected children is associated with a decrease in HIV antibodies and reduced HIV reservoirs.
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- 2022
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8. Effect of Maternal Immunization With 10-Valent Pneumococcus Conjugate Vaccine (PCV-10), 23-Valent Pneumococcus Polysaccharide Vaccine, or Placebo on the Immunogenicity of PCV-10 in Human Immunodeficiency Virus-Exposed Uninfected Infants: A Randomized Clinical Trial.
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Mussi-Pinhata MM, Ward S, Laimon L, Pelton SI, Canniff J, Golner A, Bone F, Newton L, Muresan P, Fenton T, Johnson MJ, João EC, Santos BR, Pilotto JH, Oliveira RH, Pinto JA, Dal Bó AGBL, Kreitchmann R, Chakhtoura N, Duarte G, and Weinberg A
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- Antibodies, Bacterial therapeutic use, Female, HIV, Humans, Infant, Infant, Newborn, Pneumococcal Vaccines, Polysaccharides, Pregnancy, Streptococcus pneumoniae, Vaccination, Vaccines, Conjugate, HIV Infections drug therapy, Pneumococcal Infections prevention & control
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Background: The effect of pneumococcal vaccination of mothers with human immunodeficiency virus (HIV) on infant responses to childhood vaccination has not been studied. We compared the immunogenicity of 10-valent pneumococcus conjugate vaccine (PCV-10) in HIV-exposed uninfected infants born to mothers who received PCV-10, 23-valent pneumococcus polysaccharide vaccine (PPV-23), or placebo during pregnancy., Methods: Antibody levels against 7 serotypes were measured at birth, before the first and second doses of PCV-10m and after completion of the 2-dose regimen in 347 infants, including 112 born to mothers who received PPV-23, 112 who received PCV-10, and 119 who received placebo during pregnancy. Seroprotection was defined by antibody levels ≥0.35 µg/mL., Results: At birth and at 8 weeks of life, antibody levels were similar in infants born to PCV-10 or PPV-23 recipients and higher than in those born to placebo recipient. After the last dose of PCV-10, infants in the maternal PCV-10 group had significantly lower antibody levels against 5 serotypes than those in the maternal PPV-23 group and against 3 serotypes than those in the maternal placebo group, and they did not have higher antibody levels against any serotype. The seroprotection rate against 7 serotypes was 50% in infants in the maternal PCV-10 group, compared with 71% in both of the maternal PPV-23 and placebo groups (P < .001)., Conclusions: Administration of PCV-10 during pregnancy was associated with decreased antibody responses to PCV-10 and seroprotection rates in infants. Considering that PCV-10 and PPV-23 had similar immunogenicity in pregnant women with HIV and that administration of PPV-23 did not affect the immunogenicity of PCV-10 in infants, PPV-23 in pregnancy may be preferred over PCV-10., Competing Interests: Potential conflicts of interest. M. M. M. P. and G. D. report provision of PCV-10 by donation from Centro de Vigilância Epidemiológica da Secretaria da Saúde do Estado de São Paulo, São Paulo, Brazil. L. L. reports that Westat was the contract research organization contracted through the National Institutes of Health (NIH) for a task order for the current study. S. I. P. reports receipt of personal fees from Merck, Sanofi, and Pfizer; investigator-initiated grants from the NIH and Pfizer and Merck Vaccines to study surveillance of invasive pneumococcal disease, host defenses against Streptococcus pneumoniae, and the impact of severe acute respiratory syndrome coronavirus 2 on nasopharyngeal microbiome; and consulting fees from Pfizer and Merck Vaccine for participation in advisory board meetings, consulting on research projects at PAI Life Sciences and EVIDERA, and participation on a data safety and monitoring board for next-generation PCVs for Sanofi Pasteur. N. C. is employed by the NIH. A. W. has received grants from the NIH, GlaxoSmithKline, Janssen and Merck; consulting fees from Merck; and payment or honoraria from Merck. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
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- 2022
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9. Inflammasome genetic variants are associated with tuberculosis, HIV-1 infection, and TB/HIV-immune reconstitution inflammatory syndrome outcomes.
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de Sá NBR, de Souza NCS, Neira-Goulart M, Ribeiro-Alves M, Da Silva TP, Pilotto JH, Rolla VC, Giacoia-Gripp CBW, de Oliveira Pinto LM, Scott-Algara D, Morgado MG, and Teixeira SLM
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- Brazil, CARD Signaling Adaptor Proteins, Genetic Predisposition to Disease, Genotype, Humans, Inflammasomes genetics, Interleukin-18 genetics, Interleukin-33 genetics, Interleukin-6 genetics, NLR Family, Pyrin Domain-Containing 3 Protein genetics, Neoplasm Proteins genetics, Polymorphism, Single Nucleotide, HIV Infections complications, HIV Infections genetics, HIV-1, Immune Reconstitution Inflammatory Syndrome complications, Tuberculosis
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Background: Tuberculosis (TB) and AIDS are the leading causes of infectious diseases death worldwide. Here, we investigated the relationship between from single nucleotide polymorphisms (SNPs) of the NLRP3, CARD8, AIM2, CASP-1, IFI16, and IL-1β inflammasome genes, as well as the profiles of secreted proinflammatory cytokines (e.g., IL-1β, IL-18, IL-33, and IL-6) with the TB clinical profiles, TB-HIV coinfection, and IRIS onset., Methods: The individuals were divided into four groups: TB-HIV group (n=88; 11 of them with IRIS), HIV-1 group (n=20), TB group (n=24) and healthy volunteers (HC) group (n=10), and were followed up at INI/FIOCRUZ and HGNI (Rio de Janeiro/Brazil) from 2006 to 2016. Real-time PCR was used to determine the genotypes of the Single Nucleotide Polymorphism (SNPs), and ELISA was used to measure the plasma cytokine levels. Unconditional logistic regression models were used to perform risk estimations., Results: A higher risk for extrapulmonary TB was associated with the TT genotype (aOR=6.76; P=0.026) in the NLRP3 rs4612666 Single Nucleotide Polymorphism (SNP) and the C-C-T-G-C haplotype (aOR=4.99; P= 0.017) in the NLRP3 variants. This same Single Nucleotide Polymorphism (SNP) was associated with lower risk against extrapulmonary TB when the carrier allele C (aOR=0.15; P=0.021) was present. Among those with HIV-1 infections, a higher risk for TB onset was associated with the GA genotype (aOR=5.5; P=0.044) in the IL1-β rs1143634 Single Nucleotide Polymorphism (SNP). In contrast, lower risk against TB onset was associated with the A-G haplotype (aOR=0.17; P= 0.026) in the CARD8 variants. Higher IL-6 and IL-33 levels were observed in individuals with TB. A higher risk for IRIS onset was associated with CD8 counts ≤ 500 cells/mm
3 (aOR=12.32; P=0.010), the presence of extrapulmonary TB (aOR=6.6; P=0.038), and the CT genotype (aOR=61.06; P=0.026) or carrier allele T (aOR=61.06; P=0.026) in the AIM2 rs2276405 Single Nucleotide Polymorphism (SNP), whereas lower risk against IRIS onset was associated with the AT genotype (aOR=0.02; P=0.033) or carrier allele T (aOR=0.02; P=0.029) in the CARD8 rs2043211 Single Nucleotide Polymorphism (SNP) and the T-G haplotype (aOR=0.07; P= 0.033) in the CARD8 variants. No other significant associations were observed., Conclusions: Our results depict the involvement of genetic polymorphisms of crucial innate immunity genes and proinflammatory cytokines in the clinical outcomes related to TB-HIV coinfection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 de Sá, de Souza, Neira-Goulart, Ribeiro-Alves, Da Silva, Pilotto, Rolla, Giacoia-Gripp, de Oliveira Pinto, Scott-Algara, Morgado and Teixeira.)- Published
- 2022
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10. Immunogenicity of Conjugated and Polysaccharide Pneumococcal Vaccines Administered During Pregnancy or Postpartum to Women With HIV.
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Duarte G, Muresan P, Ward S, Laimon L, Pelton SI, Canniff J, Golner A, Bone F, Newton L, Fenton T, Coutinho CM, João EC, Santos BR, Pilotto JH, Oliveira RH, Pinto JA, Machado ES, Kreitchman R, Chakhtoura N, Mussi-Pinhata MM, and Weinberg A
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- Antibodies, Bacterial, Cytokines, Female, Humans, Pneumococcal Vaccines, Polysaccharides, Postpartum Period, Pregnancy, Vaccination, Vaccines, Conjugate, HIV Infections complications, Pneumococcal Infections prevention & control
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Background: Pneumococcal vaccination is recommended in people with HIV, prioritizing PCV. We compared the immunogenicity of PCV-10 and PPV-23 administered antepartum or postpartum., Methods: This double-blind study randomized 346 pregnant women with HIV on antiretrovirals to PCV-10, PPV-23, or placebo at 14-34 weeks gestational age. Women who received placebo antepartum were randomized at 24 weeks postpartum to PCV-10 or PPV-23. Antibodies against 7 serotypes common to both vaccines and 1 serotype only in PPV-23 were measured by ELISA/chemiluminescence; B- and T-cell responses to serotype 1 by FLUOROSPOT; and plasma cytokines/chemokines by chemiluminescence., Results: Antibody responses were higher after postpartum versus antepartum vaccination. PCV-10 generated lower antibody levels than PPV-23 against 4 and higher against 1 of 7 common serotypes. Additional factors associated with high postvaccination antibody concentrations were high prevaccination antibody concentrations and CD4+ cells; low CD8+ cells and plasma HIV RNA; and several plasma cytokines/chemokines. Serotype 1 B- and T-cell memory did not increase after vaccination., Conclusions: Antepartum immunization generated suboptimal antibody responses, suggesting that postpartum booster doses may be beneficial and warrant further studies. Considering that PCV-10 and PPV-23 had similar immunogenicity, but PPV-23 covered more serotypes, use of PPV-23 may be prioritized in women with HIV on antiretroviral therapy., Clinical Trails Registration: NCT02717494., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
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- 2022
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11. Sexually transmitted infections among HIV serodiscordant partners: A secondary analysis of HIV Prevention Trial Network 052.
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Chagomerana MB, Hosseinipour MC, Pilotto JH, Badal-Faesen S, Nyirenda M, Shava E, Godbole SV, Akelo V, Chariyalertsak S, Panchia R, and Cohen M
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- Chlamydia trachomatis, Female, Humans, Male, Neisseria gonorrhoeae, Prevalence, Chlamydia Infections, Gonorrhea epidemiology, Gonorrhea prevention & control, HIV Infections epidemiology, HIV Infections prevention & control, Sexually Transmitted Diseases epidemiology, Sexually Transmitted Diseases prevention & control
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Sexually transmitted infections (STIs) remain a public health concern because of their interaction(s) with HIV. In the HPTN 052 study, STIs were evaluated in both HIV-positive index cases and their HIV-negative partners at enrollment and at yearly follow-up visits. Our definition for STI was based on any infection with Chlamydia trachomatis, Neisseria gonorrhoeae , syphilis, or Trichomonas vaginalis. We used log-binomial regression models to identify factors associated with prevalent STIs. Generalized estimating equation models with the Poisson distribution were used to compare STI incidence between HIV-positive index cases and HIV-negative partners. 8.1% of the participants had STIs at enrollment. The prevalence of STIs (8.9 vs. 7.2) was higher in HIV-positive index cases than HIV-negative partners. Being female (prevalence ratio (PR) = 1.61; 95% CI: 1.20-2.16) or unmarried (PR = 1.92; 95% CI: 1.17-3.14) was associated with prevalent STIs. Compared to HIV-negative male partners, HIV-positive female index cases had a higher risk of STI acquisition (incidence rate ratio (IRR) = 2.25; 95% CI: 1.70-2.97). While we are implementing HIV prevention interventions for HIV-negative people, we should also intensify targeted STI prevention interventions, especially among HIV-positive women.
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- 2021
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12. Low prevalence of human gammaherpesvirus 8 (HHV-8) infection among HIV-infected pregnant women in Rio De Janeiro, Brazil.
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Lopes AO, Lima LRP, Tozetto-Mendoza TR, Martinelli KG, Morgado MG, Pilotto JH, and de Paula VS
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- Antibodies, Viral, Brazil epidemiology, Female, Humans, Pregnancy, Pregnant Women, Prevalence, HIV Infections complications, HIV Infections epidemiology, Herpesvirus 8, Human, Sarcoma, Kaposi
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Pregnant women coinfected with the human immunodeficiency virus (HIV) and human gammaherpesvirus 8 (HHV-8) are at higher risk of Kaposi's sarcoma development, increased viral load, and vertical transmission of these viruses. A total of 131 pregnant women infected with HIV were examined for antibodies against HHV-8 latency-associated nuclear antigen (LANA) and lytic antigens using immunofluorescence assays. The presence of HHV-8 DNA was confirmed using real-time polymerase chain reaction (qPCR) and nested PCR. Overall, 0.8% (1/131) of the patients contained antibodies to HHV-8 LANA and lytic antigens, and no HHV-8 DNA was detected. This study, including a small population of HIV-infected pregnant women in Brazil, indicates a low prevalence of HHV-8 seropositivity and absence of active infection in this group. However, a potential role of HHV-8 in the increased transmission and pathogenic activity of HIV in pregnant women is suggested. Attention should be given to the emergence of HHV-8 infection in this population group in order to avoid comorbidities and transmission of HIV.
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- 2021
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13. A randomized double-blind controlled trial of convalescent plasma in adults with severe COVID-19.
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O'Donnell MR, Grinsztejn B, Cummings MJ, Justman JE, Lamb MR, Eckhardt CM, Philip NM, Cheung YK, Gupta V, João E, Pilotto JH, Diniz MP, Cardoso SW, Abrams D, Rajagopalan KN, Borden SE, Wolf A, Sidi LC, Vizzoni A, Veloso VG, Bitan ZC, Scotto DE, Meyer BJ, Jacobson SD, Kantor A, Mishra N, Chauhan LV, Stone EF, Dei Zotti F, La Carpia F, Hudson KE, Ferrara SA, Schwartz J, Stotler BA, Lin WW, Wontakal SN, Shaz B, Briese T, Hod EA, Spitalnik SL, Eisenberger A, and Lipkin WI
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- Adult, Aged, Aged, 80 and over, Brazil epidemiology, COVID-19 immunology, COVID-19 mortality, Double-Blind Method, Female, Humans, Immunization, Passive, Kaplan-Meier Estimate, Male, Middle Aged, New York City epidemiology, Pandemics, Severity of Illness Index, Treatment Outcome, COVID-19 Serotherapy, COVID-19 therapy, SARS-CoV-2 immunology
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BACKGROUNDAlthough convalescent plasma has been widely used to treat severe coronavirus disease 2019 (COVID-19), data from randomized controlled trials that support its efficacy are limited.METHODSWe conducted a randomized, double-blind, controlled trial among adults hospitalized with severe and critical COVID-19 at 5 sites in New York City (USA) and Rio de Janeiro (Brazil). Patients were randomized 2:1 to receive a single transfusion of either convalescent plasma or normal control plasma. The primary outcome was clinical status at 28 days following randomization, measured using an ordinal scale and analyzed using a proportional odds model in the intention-to-treat population.RESULTSOf 223 participants enrolled, 150 were randomized to receive convalescent plasma and 73 to receive normal control plasma. At 28 days, no significant improvement in the clinical scale was observed in participants randomized to convalescent plasma (OR 1.50, 95% confidence interval [CI] 0.83-2.68, P = 0.180). However, 28-day mortality was significantly lower in participants randomized to convalescent plasma versus control plasma (19/150 [12.6%] versus 18/73 [24.6%], OR 0.44, 95% CI 0.22-0.91, P = 0.034). The median titer of anti-SARS-CoV-2 neutralizing antibody in infused convalescent plasma units was 1:160 (IQR 1:80-1:320). In a subset of nasopharyngeal swab samples from Brazil that underwent genomic sequencing, no evidence of neutralization-escape mutants was detected.CONCLUSIONIn adults hospitalized with severe COVID-19, use of convalescent plasma was not associated with significant improvement in day 28 clinical status. However, convalescent plasma was associated with significantly improved survival. A possible explanation is that survivors remained hospitalized at their baseline clinical status.TRIAL REGISTRATIONClinicalTrials.gov, NCT04359810.FUNDINGAmazon Foundation, Skoll Foundation.
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- 2021
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14. Dried blood spot sampling as an alternative for the improvement of hepatitis B and C diagnosis in key populations.
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Flores GL, Barbosa JR, Cruz HM, Miguel JC, Potsch DV, Pilotto JH, Lima DM, Baima Colares JK, Brandão-Mello CE, Pires MMA, da Mota JC, Bastos FI, Lewis-Ximenez LL, and Villar LM
- Abstract
Background: To achieve the elimination of hepatitis B and C, there is an urgent need to develop alternative strategies to increase the access of diagnosis, particularly among key populations such as people living with human immunodeficiency virus (HIV), individuals with coagulopathies and chronic kidney disease (CKD) patients., Aim: To evaluate the use of dried blood spot (DBS) in the detection of hepatitis B virus (HBV) and hepatitis C virus (HCV) markers., Methods: A total of 430 individuals comprised of people living with HIV, coagulopathies and CKD provided paired serum and DBS samples. HBsAg, anti-HBc and anti-HCV were tested in those samples using a commercial electrochemiluminescence. Demographic and selected behavioral variables were evaluated to assess possible association with HBV and HCV positivity., Results: Using DBS, HBsAg prevalence varied from 3.9% to 22.1%, anti-HBc rates varied from 25.5% to 45.6% and anti-HCV positivity ranged from 15.9% to 41.2% in key populations. Specificities of HBV and HCV tests using DBS varied from 88.9% to 100%. The HBsAg assay demonstrated the best performance in CKD and coagulopathy individuals and the anti-HCV test had a sensitivity and specificity of 100% in people living with HIV. Accuracy of HBV and HCV detection in DBS varied from 90.2% to 100%. In the CKD group, HBsAg positivity was associated with infrequent use of condoms, and anti-HBc positivity was associated with sharing nail cutters/razors/toothbrushes. Anti-HCV reactivity was positively associated with a history of transplantation and length of time using hemodialysis in both specimens. In people living with HIV, only the male gender was associated with anti-HBc positivity in serum and DBS., Conclusion: DBS with electrochemiluminescence are useful tools for the diagnosis and prevalence studies of hepatitis B and C among key populations and may increase the opportunity to foster prevention and treatment., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)
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- 2021
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15. Evaluation of Phylogenetic Methods for Inferring the Direction of Human Immunodeficiency Virus (HIV) Transmission: HIV Prevention Trials Network (HPTN) 052.
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Zhang Y, Wymant C, Laeyendecker O, Grabowski MK, Hall M, Hudelson S, Piwowar-Manning E, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Mills LA, Santos BR, Grinsztejn B, Pilotto JH, Chariyalertsak S, Makhema J, Chen YQ, Cohen MS, Fraser C, and Eshleman SH
- Subjects
- Humans, Phylogeny, HIV Infections prevention & control, HIV-1 genetics
- Abstract
Background: Phylogenetic analysis can be used to assess human immunodeficiency virus (HIV) transmission in populations. We inferred the direction of HIV transmission using whole-genome HIV sequences from couples with known linked infection and known transmission direction., Methods: Complete next-generation sequencing (NGS) data were obtained for 105 unique index-partner sample pairs from 32 couples enrolled in the HIV Prevention Trials Network (HPTN) 052 study (up to 2 samples/person). Index samples were obtained up to 5.5 years before partner infection; partner samples were obtained near the time of seroconversion. The bioinformatics method, phyloscanner, was used to infer transmission direction. Analyses were performed using samples from individual sample pairs, samples from all couples (1 sample/person; group analysis), and all available samples (multisample group analysis). Analysis was also performed using NGS data from defined regions of the HIV genome (gag, pol, env)., Results: Using whole-genome NGS data, transmission direction was inferred correctly (index to partner) for 98 of 105 (93.3%) of the individual sample pairs, 99 of 105 (94.3%) sample pairs using group analysis, and 31 of the 32 couples (96.9%) using multisample group analysis. There were no cases where the incorrect transmission direction (partner to index) was inferred. The accuracy of the method was higher with greater time between index and partner sample collection. Pol region sequences performed better than env or gag sequences for inferring transmission direction., Conclusions: We demonstrate the potential of a phylogenetic method to infer the direction of HIV transmission between 2 individuals using whole-genome and pol NGS data., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Published
- 2021
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16. Neutrophil extracellular traps from healthy donors and HIV-1-infected individuals restrict HIV-1 production in macrophages.
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Mojoli A, Gonçalves BS, Temerozo JR, Cister-Alves B, Geddes V, Herlinger A, Aguiar RS, Pilotto JH, Saraiva EM, and Bou-Habib DC
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- Cell Survival, Cells, Cultured, Chemokines, CC metabolism, DNA, Viral metabolism, HIV Infections virology, HIV-1 pathogenicity, Humans, Macrophages metabolism, Neutrophils virology, Virus Replication physiology, Extracellular Traps genetics, HIV Infections blood, HIV-1 physiology, Macrophages virology, Neutrophils cytology
- Abstract
Neutrophils release extracellular traps (NETs) after interaction with microorganisms and physiological or synthetic products. NETs consist of decondensed chromatin complexed with proteins, some of them with microbicidal properties. Because NETs can modulate the functioning of HIV-1 target cells, we aimed to verify whether they modify HIV-1 replication in macrophages. We found that exposure of HIV-1-infected macrophages to NETs resulted in significant inhibition of viral replication. The NET anti-HIV-1 action was independent of other soluble factors released by the activated neutrophils, but otherwise dependent on the molecular integrity of NETs, since NET-treatment with protease or DNase abolished this effect. NETs induced macrophage production of the anti-HIV-1 β-chemokines Rantes and MIP-1β, and reduced the levels of integrated HIV-1 DNA in the macrophage genome, which may explain the decreased virus production by infected macrophages. Moreover, the residual virions released by NET-treated HIV-1-infected macrophages lost infectivity. In addition, elevated levels of DNA-elastase complexes were detected in the plasma from HIV-1-infected individuals, and neutrophils from these patients released NETs, which also inhibited HIV-1 replication in in vitro infected macrophages. Our results reveal that NETs may function as an innate immunity mechanism able to restrain HIV-1 production in macrophages.
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- 2020
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17. Utilizing an HIV community advisory board as an agent of community action and health promotion in a low-resource setting: a case-study from Nova Iguaçu, Rio de Janeiro, Brazil.
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Milnor JR, Santana CS, Martos AJ, Pilotto JH, and Souza CTV
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- Adolescent, Brazil, Community Participation, Female, Homosexuality, Male, Humans, Male, HIV Infections, Health Promotion, Sexual and Gender Minorities
- Abstract
Introduction: Brazil's HIV burden has greatly increased over the past decade, especially for socially marginalized and vulnerable groups such as adolescents, women, and men who have sex with men. The reasoning for worsening HIV outcomes is complex, but ongoing economic and political crises have placed extreme operational and financial burdens on both the public health system and HIV-related civil society, affecting both treatment and prevention efforts and delivery., Context: Community-based HIV-related health-promotion activities have continued in Nova Iguaçu, Rio de Janeiro, despite these setbacks. These efforts have been led by a semi-independent community advisory board and engagement group based at the Hospital Geral de Nova Iguaçu with support from researchers based at the Oswaldo Cruz Foundation., Methods: The research team supported, documented, and participated in various activities led by the community advisory board and engagement group from 2017-2018 including meetings, community workshops/lectures, production of health promotion materials, and the dissemination of research findings., Results: The research team utilized the concepts of vernacular knowledge and critical pedagogy to describe and document the ongoing, bottom-up approach, community-led efforts of the community advisory board and engagement group. In particular, we describe the process of stakeholder engagement, popularization of research results, and resource sharing spearheaded by the community advisory board in Nova Iguaçu., Conclusion: The community advisory board demonstrates how community-led efforts are essential to HIV and AIDS response efforts in light of worsening HIV burdens and global shifts towards biomedicalization. Their HIV-related activities rely on existing community networks and resources with secondary support from a research team. This illustrates a key intervention point between traditional research and an empowering community mobilization that can inform similar efforts in other low-resource settings.
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- 2020
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18. Clinical and genetic markers associated with tuberculosis, HIV-1 infection, and TB/HIV-immune reconstitution inflammatory syndrome outcomes.
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de Sá NBR, Ribeiro-Alves M, da Silva TP, Pilotto JH, Rolla VC, Giacoia-Gripp CBW, Scott-Algara D, Morgado MG, and Teixeira SLM
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- Brazil, Coinfection drug therapy, Coinfection genetics, Coinfection pathology, Female, Follow-Up Studies, Gene Frequency genetics, Genetic Markers, Genotype, HIV Infections drug therapy, HIV Infections pathology, HLA-B Antigens genetics, HLA-C Antigens genetics, Humans, Immune Reconstitution Inflammatory Syndrome pathology, Male, Receptors, KIR genetics, Sex Factors, Tuberculosis drug therapy, Tuberculosis pathology, HIV Infections complications, HIV Infections genetics, HIV-1, Immune Reconstitution Inflammatory Syndrome etiology, Immune Reconstitution Inflammatory Syndrome genetics, Tuberculosis complications, Tuberculosis genetics
- Abstract
Background: Tuberculosis (TB) and AIDS are the leading causes of infectious disease death worldwide. In some TB-HIV co-infected individuals treated for both diseases simultaneously, a pathological inflammatory reaction termed immune reconstitution inflammatory syndrome (IRIS) may occur. The risk factors for IRIS are not fully defined. We investigated the association of HLA-B, HLA-C, and KIR genotypes with TB, HIV-1 infection, and IRIS onset., Methods: Patients were divided into four groups: Group 1- TB+/HIV+ (n = 88; 11 of them with IRIS), Group 2- HIV+ (n = 24), Group 3- TB+ (n = 24) and Group 4- healthy volunteers (n = 26). Patients were followed up at INI/FIOCRUZ and HGNI (Rio de Janeiro/Brazil) from 2006 to 2016. The HLA-B and HLA-C loci were typed using SBT, NGS, and KIR genes by PCR-SSP. Unconditional logistic regression models were performed for Protection/risk estimation., Results: Among the individuals with TB as the outcome, KIR2DS2 was associated with increased risk for TB onset (aOR = 2.39, P = 0.04), whereas HLA-B*08 and female gender were associated with protection against TB onset (aOR = 0.23, P = 0.03, and aOR = 0.33, P = 0.01, respectively). Not carrying KIR2DL3 (aOR = 0.18, P = 0.03) and carrying HLA-C*07 (aOR = 0.32, P = 0.04) were associated with protection against TB onset among HIV-infected patients. An increased risk for IRIS onset was associated with having a CD8 count ≤500 cells/mm
3 (aOR = 18.23, P = 0.016); carrying the KIR2DS2 gene (aOR = 27.22, P = 0.032), the HLA-B*41 allele (aOR = 68.84, P = 0.033), the KIR2DS1 + HLA-C2 pair (aOR = 28.58, P = 0.024); and not carrying the KIR2DL3 + HLA-C1/C2 pair (aOR = 43.04, P = 0.034), and the KIR2DL1 + HLA-C1/C2 pair (aOR = 43.04, P = 0.034), CONCLUSIONS: These results suggest the participation of these genes in the immunopathogenic mechanisms related to the conditions studied. This is the first study demonstrating an association of HLA-B*41, KIR2DS2, and KIR + HLA-C pairs with IRIS onset among TB-HIV co-infected individuals.- Published
- 2020
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19. Impact of Raltegravir or Efavirenz on Cell-Associated Human Immunodeficiency Virus-1 (HIV-1) Deoxyribonucleic Acid and Systemic Inflammation in HIV-1/Tuberculosis Coinfected Adults Initiating Antiretroviral Therapy.
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Delagreverie HM, Bauduin C, De Castro N, Grinsztejn B, Chevrier M, Jouenne F, Mourah S, Kalidi I, Pilotto JH, Brites C, Tregnago Barcellos N, Amara A, Wittkop L, Molina JM, and Delaugerre C
- Abstract
Background: In view of the fast viremia decline obtained with integrase inhibitors, we studied the respective effects of initiating efavirenz (EFV) or raltegravir (RAL)-based antiretroviral therapy (ART) regimens on human immunodeficiency virus (HIV)-1 deoxyribonucleic acid (DNA) levels and inflammation biomarkers in the highly inflammatory setting of advanced HIV-1 disease with tuberculosis (TB) coinfection., Methods: We followed cell-associated HIV-1 DNA, high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), soluble CD14 and D-Dimer levels for 48 weeks after ART initiation in the participants to the ANRS12-180 REFLATE-TB study. This phase II open-label randomized study included ART-naive people with HIV and TB treated with rifampicin to receive RAL 400 mg twice daily (RAL400), RAL 800 mg twice daily (RAL800) or EFV 600 mg QD with tenofovir and lamivudine., Results: In 146 participants, the median (interquartile range [IQR]) week (W)0 HIV-1 DNA level was 4.7 (IQR, 4.3-5.1) log
10 copies/106 CD4+ , and the reduction by W48 was -0.8 log10 copies/106 CD4+ on EFV, -0.9 on RAL400, and -1.0 on RAL800 ( P = .74). Baseline median (IQR) hsCRP, IL-6, sCD14, and D-Dimer levels were 6.9 (IQR, 3.3-15.6) mg/L, 7.3 (IQR, 3.5-12.3) pg/mL, 3221 (IQR, 2383-4130) ng/mL, and 975 (IQR, 535-1970) ng/mL. All biomarker levels decreased over the study: the overall W0-W48 mean (95% confidence interval) fold-change on ART was 0.37 (IQR, 0.28-0.48) for hsCRP, 0.42 (IQR, 0.35-0.51) for IL-6, 0.51 (IQR, 0.47-0.56) for sCD14, and 0.39 (IQR, 0.32-0.47) for D-Dimers. There were no differences in biomarker reduction across treatment arms., Conclusions: In participants with HIV and TB, EFV, RAL400, or RAL800 effectively and equally reduced inflammation and HIV-1 DNA levels., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)- Published
- 2020
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20. Self-collected versus clinician-collected samples for HSV-2 and HSV-2/HPV screening in HIV-infected and -uninfected women in the Tapajós region, Amazon, Brazil.
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Rodrigues LL, Pilotto JH, Lima LR, Gaydos CA, Hardick J, Morgado MG, Martinelli KG, de Paula VS, and Nicol AF
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- Adolescent, Adult, Brazil epidemiology, Case-Control Studies, Coinfection epidemiology, Cross-Sectional Studies, HIV Infections blood, HIV Infections epidemiology, HIV Infections virology, Herpesvirus 2, Human genetics, Humans, Mass Screening statistics & numerical data, Papillomaviridae genetics, Papillomavirus Infections virology, Polymerase Chain Reaction, Predictive Value of Tests, Reproducibility of Results, Self Care, DNA, Viral isolation & purification, Herpesvirus 2, Human isolation & purification, Mass Screening methods, Papillomaviridae isolation & purification, Papillomavirus Infections diagnosis, Papillomavirus Infections epidemiology, Specimen Handling methods
- Published
- 2019
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21. Phylogenetic Methods Inconsistently Predict the Direction of HIV Transmission Among Heterosexual Pairs in the HPTN 052 Cohort.
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Rose R, Hall M, Redd AD, Lamers S, Barbier AE, Porcella SF, Hudelson SE, Piwowar-Manning E, McCauley M, Gamble T, Wilson EA, Kumwenda J, Hosseinipour MC, Hakim JG, Kumarasamy N, Chariyalertsak S, Pilotto JH, Grinsztejn B, Mills LA, Makhema J, Santos BR, Chen YQ, Quinn TC, Fraser C, Cohen MS, Eshleman SH, and Laeyendecker O
- Subjects
- Cohort Studies, Female, HIV isolation & purification, HIV Infections transmission, Heterosexuality, High-Throughput Nucleotide Sequencing, Humans, Male, env Gene Products, Human Immunodeficiency Virus genetics, Disease Transmission, Infectious, Genotype, HIV classification, HIV genetics, HIV Infections virology, Molecular Epidemiology methods, Phylogeny
- Abstract
Background: We evaluated use of phylogenetic methods to predict the direction of human immunodeficiency virus (HIV) transmission., Methods: For 33 pairs of HIV-infected patients (hereafter, "index patients") and their partners who acquired genetically linked HIV infection during the study, samples were collected from partners and index patients close to the time when the partner seroconverted (hereafter, "SC samples"); for 31 pairs, samples collected from the index patient at an earlier time point (hereafter, "early index samples") were also available. Phylogenies were inferred using env next-generation sequences (1 tree per pair/subtype). The direction of transmission (DoT) predicted from each tree was classified as correct or incorrect on the basis of which sequences (those from the index patient or the partner) were closest to the root. DoT was also assessed using maximum parsimony to infer ancestral node states for 100 bootstrap trees., Results: DoT was predicted correctly for both single-pair and subtype-specific trees in 22 pairs (67%) by using SC samples and in 23 pairs (74%) by using early index samples. DoT was predicted incorrectly for 4 pairs (15%) by using SC or early index samples. In the bootstrap analysis, DoT was predicted correctly for 18 pairs (55%) by using SC samples and for 24 pairs (73%) by using early index samples. DoT was predicted incorrectly for 7 pairs (21%) by using SC samples and for 4 pairs (13%) by using early index samples., Conclusions: Phylogenetic methods based solely on the tree topology of HIV env sequences, particularly without consideration of phylogenetic uncertainty, may be insufficient for determining DoT., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Published
- 2019
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22. Accuracy of Determine TB-LAM Ag to detect TB in HIV infected patients associated with diagnostic methods used in Brazilian public health units.
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Benjamin A, Cavalcante SC, Jamal LF, Arakaki-Sanchez D, de Lima JN, Pilotto JH, de Oliveira Junior FI, Souza TNL, Lourenço MC, de Mello MB, do Brasil PEAA, Barreira D, and Rolla V
- Subjects
- Adult, Brazil epidemiology, CD4 Lymphocyte Count, Cross-Sectional Studies, Female, HIV Infections epidemiology, HIV Infections virology, Humans, Male, Middle Aged, Public Health Surveillance, Radiography, Thoracic, Sensitivity and Specificity, Tuberculosis epidemiology, Tuberculosis microbiology, Coinfection, Diagnostic Tests, Routine methods, Diagnostic Tests, Routine standards, HIV Infections diagnosis, Point-of-Care Testing, Tuberculosis diagnosis
- Abstract
Background: Determine TB-LAM Ag (LAM) is a point of care test developed to diagnose tuberculosis (TB). The aim of this study was to evaluate the diagnostic performance of LAM in people living with HIV using Brazilian public health network algorithm for TB diagnosis., Methods and Findings: A cross-sectional study design was used to enroll 199 adult patients in two sites in Rio de Janeiro and two in São Paulo. The study enrolled HIV-infected patients with CD4 counts ≤200 cells/mm3 (in the Alere PIMA CD4 assay at study screening), patients coughing for at least 2 weeks or presenting a chest radiography suggestive of TB. LAM, in conjunction with sputum smear microscopy or Xpert MTB/RIF (Xpert) as compared to Mycobacterium tuberculosis culture, which was used as a reference standard. TB prevalence was 24.6%. Overall accuracy of LAM was 79.9% (73.8%-84.9%), positive and negative predictive values were 62.2% (46.1%-75.9%) and 84% (77.5%-88.8%), respectively. The overall LAM sensitivity was 46.9% (33.7%-60.6%) and specificity was 90.7% (84.9%-94.4%). The best performance of LAM was observed among patients with CD4 counts ≤50 cells/mm3 (sensitivity = 70.4% and specificity = 85.9%). When 2 respiratory smears were used in conjunction with LAM, sensitivity increased 22%, as compared to just 2 smears. Furthermore, LAM when used in conjunction with two respiratory smears, was as sensitive as compared to a single one. However, no improvement in TB diagnosis occurred when LAM was used with Xpert as compared to Xpert alone. Among 14 LAM false positive tests, Non-Tuberculosis Mycobacteria were isolated in three cases., Conclusion: LAM is a point of care test that increased TB diagnosis in immunosuppressed HIV-infected patients when used in conjunction with smear microscopy, but not when used with Xpert in Brazilian public health network sites. Use of LAM test should be considered in settings where immunosuppressed HIV patients need rapid TB diagnosis., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2019
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23. Changes in the NK Cell Repertoire Related to Initiation of TB Treatment and Onset of Immune Reconstitution Inflammatory Syndrome in TB/HIV Co-infected Patients in Rio de Janeiro, Brazil-ANRS 12274.
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Giacoia-Gripp CBW, Cazote ADS, da Silva TP, Sant'Anna FM, Schmaltz CAS, Brum TS, de Matos JA, Silva J, Benjamin A, Pilotto JH, Rolla VC, Morgado MG, and Scott-Algara D
- Subjects
- Adult, Anti-HIV Agents therapeutic use, Antitubercular Agents therapeutic use, Brazil, Coinfection immunology, Female, Flow Cytometry, Follow-Up Studies, HIV Infections complications, HIV Infections drug therapy, Humans, Immune Reconstitution Inflammatory Syndrome etiology, Immunity, Innate, Male, Middle Aged, T-Lymphocyte Subsets immunology, Treatment Outcome, Tuberculosis, Pulmonary complications, Tuberculosis, Pulmonary drug therapy, HIV Infections immunology, Immune Reconstitution Inflammatory Syndrome immunology, Killer Cells, Natural immunology, Tuberculosis, Pulmonary immunology
- Abstract
Tuberculosis (TB) is the most common comorbidity and the leading cause of death among HIV-infected individuals. Although the combined antiretroviral therapy (cART) during TB treatment improves the survival of TB/HIV patients, the occurrence of immune reconstitution inflammatory syndrome (IRIS) in some patients poses clinical and scientific challenges. This work aimed to evaluate blood innate lymphocytes during therapeutic intervention for both diseases and their implications for the onset of IRIS. Natural killer (NK) cells, invariant NKT cells (iNKT), γδ T cell subsets, and in vitro NK functional activity were characterized by multiparametric flow cytometry in the following groups: 33 TB/HIV patients (four with paradoxical IRIS), 27 TB and 25 HIV mono-infected subjects (prior to initiation of TB treatment and/or cART and during clinical follow-up to 24 weeks), and 25 healthy controls (HC). Concerning the NK cell repertoire, several activation and inhibitory receptors were skewed in the TB/HIV patients compared to those in the other groups, especially the HCs. Significantly higher expression of CD158a ( p = 0.025), NKp80 ( p = 0.033), and NKG2C ( p = 0.0076) receptors was detected in the TB/HIV IRIS patients than in the non-IRIS patients. Although more NK degranulation was observed in the TB/HIV patients than in the other groups, the therapeutic intervention did not alter the frequency during follow-up (weeks 2-24). A higher frequency of the γδ T cell population was observed in the TB/HIV patients with inversion of the Vδ2
+ /Vδ2- ratio, especially for those presenting pulmonary TB, suggesting an expansion of particular γδ T subsets during TB/HIV co-infection. In conclusion, HIV infection impacts the frequency of circulating NK cells and γδ T cell subsets in TB/HIV patients. Important modifications of the NK cell repertoire were observed after anti-TB treatment (week 2) but not during the cART/TB follow-up (weeks 6-24). An increase of CD161+ NK cells was related to an unfavorable outcome. Despite the low number of cases, a more preserved NK cell profile was detected in IRIS patients previous to treatment, suggesting a role for these cells in IRIS onset. Longitudinal evaluation of the NK repertoire showed the impact of TB treatment and implicated these cells in TB pathogenesis in TB/HIV co-infected patients.- Published
- 2019
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24. Sexually transmitted infections among HIV-infected and HIV-uninfected women in the Tapajós region, Amazon, Brazil: Self-collected vs. clinician-collected samples.
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Rodrigues LLS, Hardick J, Nicol AF, Morgado MG, Martinelli KG, de Paula VS, Pilotto JH, and Gaydos CA
- Subjects
- Adolescent, Adult, Brazil epidemiology, Cervix Uteri microbiology, Cervix Uteri virology, Chlamydia trachomatis, Cross-Sectional Studies, Female, HIV-1, Humans, Mass Screening, Middle Aged, Mycoplasma genitalium, Neisseria gonorrhoeae, Papillomaviridae, Trichomonas vaginalis, Chlamydia Infections epidemiology, Chlamydia Infections microbiology, Chlamydia Infections virology, Coinfection epidemiology, Coinfection microbiology, Coinfection virology, Gonorrhea epidemiology, Gonorrhea microbiology, Gonorrhea virology, HIV Infections epidemiology, HIV Infections microbiology, HIV Infections virology, Mycoplasma Infections epidemiology, Mycoplasma Infections microbiology, Mycoplasma Infections virology, Papillomavirus Infections epidemiology, Papillomavirus Infections microbiology, Papillomavirus Infections virology, Specimen Handling, Trichomonas Vaginitis epidemiology, Trichomonas Vaginitis microbiology, Trichomonas Vaginitis virology
- Abstract
The anogenital prevalence of sexually transmitted infections (STIs) and the use of cervico-vaginal self-collected vs. clinician-collected samples were evaluated for the diagnosis of human immunodeficiency virus (HIV)-infected and HIV-uninfected women in the Tapajós region, Amazon, Brazil. We recruited 153 women for a cross-sectional study (112 HIV-uninfected and 41 HIV-infected) who sought health services. Anal and cervical scrapings and cervico-vaginal self-collection samples were collected. Real-time polymerase chain reaction methods were used for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis and Mycoplasma genitalium. A syphilis test was also performed. Risk factors for STIs were identified by multivariate analysis. The overall prevalence of STIs was 30.4% (34/112) in HIV-uninfected women and 24.4% (10/41) in HIV-infected women. Anogenital Chlamydia trachomatis infection was the most prevalent in both groups of women (20.5% vs 19.5%). There was significant agreement for each STI between self-collected and clinician-collected samples: 91.7%, kappa 0.67, 95% confidence interval (CI) 0.49-0.85 for Chlamydia trachomatis; 99.2%, kappa 0.85, 95% CI 0.57-1.00 for Neisseria gonorrhoeae; 97.7%, kappa 0.39, 95% CI -0.16-0.94 for Trichomonas vaginalis; and 94.7%, kappa 0.51, 95% CI 0.20-0.82 for Mycoplasma genitalium. Women with human papillomavirus had coinfection or multiple infections with other STIs. Risk factors for STIs were being ≤ 25 years old, being employed or a student, reporting a history of STI and having a positive HPV test. A high prevalence of STIs in women in the Tapajós region was found. Cervico-vaginal self-collection is a useful tool for STI screening and can be used in prevention control programs in low-resource settings, such as in northern Brazil., Competing Interests: The authors have declared that no competing interests exist.
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- 2019
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25. Adverse Pregnancy Outcomes Among Women Who Conceive on Antiretroviral Therapy.
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Hoffman RM, Brummel SS, Britto P, Pilotto JH, Masheto G, Aurpibul L, Joao E, Purswani MU, Buschur S, Pierre MF, Coletti A, Chakhtoura N, Klingman KL, and Currier JS
- Subjects
- Adult, Anti-Retroviral Agents administration & dosage, Female, Humans, Pregnancy, Young Adult, Abortion, Spontaneous chemically induced, Anti-Retroviral Agents adverse effects, Anti-Retroviral Agents therapeutic use, HIV Infections drug therapy, Stillbirth
- Abstract
Background: Adverse pregnancy outcomes for women who conceive on antiretroviral therapy (ART) may be increased, but data are conflicting., Methods: Human immunodeficiency virus-infected, nonbreastfeeding women with pre-ART CD4 counts ≥400 cells/μL who started ART during pregnancy were randomized after delivery to continue ART (CTART) or discontinue ART (DCART). Women randomized to DCART were recommended to restart if a subsequent pregnancy occurred or for clinical indications. Using both intent-to-treat and as-treated approaches, we performed Fisher exact tests to compare subsequent pregnancy outcomes by randomized arm., Results: Subsequent pregnancies occurred in 277 of 1652 (17%) women (CTART: 144/827; DCART: 133/825). A pregnancy outcome was recorded for 266 (96%) women with a median age of 27 years (interquartile range [IQR], 24-31 years) and median CD4+ T-cell count 638 cells/μL (IQR, 492-833 cells/μL). When spontaneous abortions and stillbirths were combined, there was a significant difference in events, with 33 of 140 (23.6%) in the CTART arm and 15 of 126 (11.9%) in the DCART arm (relative risk [RR], 2.0 [95% confidence interval {CI}, 1.1-3.5]; P = .02). In the as-treated analysis, the RR was reduced and no longer statistically significant (RR, 1.4 [95% CI, .8-2.4])., Conclusions: Women randomized to continue ART who subsequently conceived were more likely to have spontaneous abortion or stillbirth, compared with women randomized to stop ART; however, the findings did not remain significant in the as-treated analysis. More data are needed on pregnancy outcomes among women conceiving on ART, particularly with newer regimens.
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- 2019
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26. Novel variants of human herpesvirus 2 from Brazilian HIV-1 coinfected subjects.
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Lima LRP, Araújo NA, Guterres A, Pilotto JH, Niel C, and Paula VS
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- Brazil, Coinfection virology, Female, HIV Infections complications, Herpes Genitalis complications, Humans, Phylogeny, Polymerase Chain Reaction, Genes, Viral genetics, HIV Infections virology, HIV-1, Herpes Genitalis virology, Herpesvirus 2, Human genetics
- Abstract
BACKGROUND Human herpesvirus 2 (HHV-2) have DNA genome with a limited genetic variability and have been classified into two clades. OBJECTIVES To identify and characterise six HHV-2 isolates derived from Brazilian women. METHODS HHV-2 isolates were performed polymerase chain reaction (PCR) and sequencing of 2250 pb of the glycoprotein B (gB) coding regions. FINDINGS Four HHV-2 isolates were classified into clade B, while the remaining two, derived from HIV-1 co-infected women, showed a notable genetic divergence (> 1%). MAIN CONCLUSION The results reveal novel HHV-2 variants. The impact of these novel variants on HHV-2 pathogenesis and HIV/HHV-2 coinfection need to be investigated.
- Published
- 2018
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27. Assessing hepatitis B immunity using dried blood spot samples from HIV+ individuals.
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Flores GL, Cruz HM, Miguel JC, Potsch DV, Pilotto JH, Lewis-Ximenez LL, Lampe E, and Villar LM
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- Adolescent, Adult, Aged, Aged, 80 and over, Female, Hepatitis B Surface Antigens immunology, Humans, Immunoenzyme Techniques methods, Male, Middle Aged, Sensitivity and Specificity, Young Adult, Desiccation, HIV Infections, Hepatitis B immunology, Hepatitis B Antibodies blood, Hepatitis B virus immunology, Mass Screening methods, Specimen Handling methods
- Abstract
This study aims to evaluate the utility of an optimized enzyme immunoassay (EIA) to detect and quantify antibodies against hepatitis B surface antibody (anti-HBs) in dried blood spots (DBSs) within the context of human immunodeficiency virus (HIV) status. Serum and DBS samples were obtained from 56 HIV+ and 99 HIV- patients and subjected to EIA for the detection of anti-HBs, where sample volume and cut off value were modified for DBS testing. Sensitivities of anti-HBs detection in DBS were 79.8% and 76.8% in HIV- and HIV+ subjects, respectively. Concordant results for anti-HBs in serum and DBS presented high mean CD8 cell counts, HIV viral load and optical density (OD) values of anti-HBs. Anti-HBs titers were significantly higher in serum, whether or not anti-HBs titers were detected in DBS. It was possible to detect anti-HBs in DBS as low as 17.4 and 27.3 IU/mL among HIV+ and HIV- subjects, respectively. In conclusion, DBS can be used to detect and quantify anti-HBs in HIV-infected individuals, which could increase access to diagnosis and vaccination., (© 2018 Wiley Periodicals, Inc.)
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- 2018
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28. Infectious Morbidity, Mortality and Nutrition in HIV-exposed, Uninfected, Formula-fed Infants: Results From the HPTN 040/PACTG 1043 Trial.
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Yeganeh N, Watts DH, Xu J, Kerin T, Joao EC, Pilotto JH, Theron G, Gray G, Santos B, Fonseca R, Kreitchmann R, Pinto J, Mussi-Pinhata MM, Veloso V, Camarca M, Mofenson L, Moye J, and Nielsen-Saines K
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- Brazil epidemiology, Cause of Death, Female, Follow-Up Studies, HIV Infections drug therapy, HIV Infections mortality, Humans, Infant, Infant Formula, Male, Malnutrition epidemiology, Malnutrition etiology, Nutritional Status, Pregnancy, Pregnancy Complications, Infectious drug therapy, Pregnancy Complications, Infectious mortality, Risk Factors, South Africa epidemiology, Viral Load, Anti-HIV Agents therapeutic use, HIV Infections complications, Infant Mortality, Infectious Disease Transmission, Vertical statistics & numerical data
- Abstract
Background: HIV-exposed uninfected (HEU) infants are a growing population with potentially poor health outcomes. We evaluated morbidity and mortality in HEU formula-fed infants enrolled in the NICHD HPTN 040/PACTG 1043 trial., Methods: Infectious morbidity, mortality and undernutrition were evaluated within a cohort of 1000 HEU infants enrolled between April 2004 and April 2010 in Brazil (n = 766) and South Africa (n = 234) as part of the NICHD/HPTN 040 trial of 3 different antiretroviral regimens to decrease intrapartum HIV vertical transmission., Results: Twenty-three percent of infants had at least 1 infectious serious adverse effect. Infants born to mothers with <12 years of education [adjusted odds ratio (AOR), 2.6; 95% confidence interval [CI], 1.2-5.9), with maternal viral load of >1,000,000 copies/mL at delivery (AOR, 9.9; 95% CI, 1.6-63.1) were more likely to have infectious serious adverse effects. At 6 months, the infant mortality rate per 1000 live births overall was 22 ± 2.6, 9.1 ± 1.8 in Brazil and 64.1 ± 3 in South Africa. Undernutrition and stunting peaked at 1 month of age with 18% having a weight-for-age Z score ≤-2, and 22% with height for Z score ≤-2. The likelihood of infant mortality was greater among infants born in South Africa compared with Brazil (AOR, 6.2; 95% CI, 2.5-15.8), high maternal viral load (AOR, 1.7; 95% CI, 1.01-2.9) and birth weight-for-age Z score ≤-2 (AOR, 5.2; 95% CI, 1.8-14.8)., Conclusions: There were high rates of undernutrition, stunting and infectious serious adverse effect in this study's formula-fed HEU population. Suppressing maternal HIV viral load during the peripartum period may be a modifiable risk factor to decrease infant mortality.
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- 2018
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29. Chlamydia trachomatis asymptomatic urethritis recurrence among males living with HIV-1.
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Silva GARD, Motta HLSN, Souza EFA, Cardoso PANM, Pilotto JH, Eyer-Silva WA, Ribeiro LCP, Santos MSD, Azevedo MCVM, Pinto JFDC, Motta RN, and Ferry FRA
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- AIDS-Related Opportunistic Infections diagnosis, AIDS-Related Opportunistic Infections microbiology, Adult, Asymptomatic Infections epidemiology, Chlamydia Infections diagnosis, Humans, Male, Middle Aged, Prevalence, Prospective Studies, Recurrence, Risk Factors, Urethritis diagnosis, Urethritis microbiology, AIDS-Related Opportunistic Infections epidemiology, Chlamydia Infections epidemiology, Chlamydia trachomatis, Urethritis epidemiology
- Abstract
A prevalence of 3.47% of asymptomatic Chlamydia trachomatis urethritis has been previously reported among males living with HIV infection in Brazil. This study aims to assess the recurrence of C. trachomatis urethritis three years later in the same cohort of patients and analyze associated risk factors. A total of 115 male patients diagnosed with HIV infection, with no symptoms of urethritis and observed since May of 2015 in followup visits were enrolled. They had urine samplers tested by PCR for C. trachomatis and N. gonorrhoeae between February and March 2018. Results: Three of the four patients who had asymptomatic C. trachomatis urethritis three years before were recurrently positive for C. trachomatis urethritis. Two new patients were diagnosed as positives, accounting for a total asymptomatic C. trachomatis urethritis prevalence of 4.34%. The prevalence during the whole study was 5.21%. The relative risk for a new urethritis episode among those previously diagnosed with urethritis is RR=41.62 (95% CI: 9.42-183.84), p < 0.01. Patients who presented asymptomatic urethritis anytime and who were recurrently positive for C. trachomatis had a lower mean age (p<0.01). Married individuals were protected regarding asymptomatic urethritis [p<0.01, OR = 0.04 (0.005-0.4)] and had lower risk to develop recurrence [p<0.01, RR = 0.86 (0.74-0.99)]. Illicit drugs users had risk associated to asymptomatic urethritis [p=0.02, OR= 5.9 (1.03-34)] and higher risk to develop recurrence [p<0.01, RR=1.1 (1-1.22)]. Conclusion: The recurrence of asymptomatic C. trachomatis urethritis after treatment among males living with HIV infection in Brazil can be considered high and should not be neglected.
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- 2018
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30. Congenital Cytomegalovirus and HIV Perinatal Transmission.
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Adachi K, Xu J, Ank B, Watts DH, Camarca M, Mofenson LM, Pilotto JH, Joao E, Gray G, Theron G, Santos B, Fonseca R, Kreitchmann R, Pinto J, Mussi-Pinhata MM, Machado DM, Ceriotto M, Morgado MG, Bryson YJ, Veloso VG, Grinsztejn B, Mirochnick M, Moye J, and Nielsen-Saines K
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- Anti-Retroviral Agents therapeutic use, Cohort Studies, Cytomegalovirus, Cytomegalovirus Infections etiology, DNA, Viral urine, Female, Humans, Infant, Infant, Newborn, Pregnancy, Real-Time Polymerase Chain Reaction, Risk Factors, Viral Load, Cytomegalovirus Infections congenital, HIV Infections complications, HIV Infections transmission, Infectious Disease Transmission, Vertical, Pregnancy Complications, Infectious virology
- Abstract
Background: Congenital cytomegalovirus (CMV) infection (cCMV) is an important cause of hearing loss and cognitive impairment. Prior studies suggest that HIV-exposed children are at higher risk of acquiring cCMV. We assessed the presence, magnitude and risk factors associated with cCMV among infants born to HIV-infected women, who were not receiving antiretrovirals during pregnancy., Methods: cCMV and urinary CMV load were determined in a cohort of infants born to HIV-infected women not receiving antiretrovirals during pregnancy. Neonatal urines obtained at birth were tested for CMV DNA by qualitative and reflex quantitative real-time polymerase chain reaction., Results: Urine specimens were available for 992 (58.9%) of 1684 infants; 64 (6.5%) were CMV-positive. Mean CMV load (VL) was 470,276 copies/ml (range: < 200-2,000,000 copies/ml). Among 89 HIV-infected infants, 16 (18%) had cCMV versus 42 (4.9%) of 858 HIV-exposed, uninfected infants (P < 0.0001). cCMV was present in 23.2% of infants with in utero and 9.1% infants with intrapartum HIV infection (P < 0.0001). Rates of cCMV among HIV-infected infants were 4-fold greater (adjusted OR, 4.4; 95% CI: 2.3-8.2) and 6-fold greater among HIV in utero-infected infants (adjusted OR, 6; 95% CI: 3-12.1) compared with HIV-exposed, uninfected infants. cCMV was not associated with mode of delivery, gestational age, Apgar scores, 6-month infant mortality, maternal age, race/ethnicity, HIV viral load or CD4 count. Primary cCMV risk factors included infant HIV-infection, particularly in utero infection., Conclusion: High rates of cCMV with high urinary CMV VL were observed in HIV-exposed infants. In utero HIV infection appears to be a major risk factor for cCMV in infants whose mothers have not received combination antiretroviral therapy in pregnancy.
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- 2018
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31. Cervico-vaginal self-collection in HIV-infected and uninfected women from Tapajós region, Amazon, Brazil: High acceptability, hrHPV diversity and risk factors.
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Rodrigues LLS, Morgado MG, Sahasrabuddhe VV, De Paula VS, Oliveira NS, Chavez-Juan E, Da Silva DM, Kast WM, Nicol AF, and Pilotto JH
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- Adolescent, Adult, Aged, Brazil epidemiology, CD4 Lymphocyte Count, Cervix Uteri pathology, Cervix Uteri virology, Cross-Sectional Studies, DNA, Viral isolation & purification, Early Detection of Cancer statistics & numerical data, Female, Genotype, HIV Infections blood, HIV Infections epidemiology, HIV Infections pathology, HIV Infections virology, Humans, Mass Screening statistics & numerical data, Middle Aged, Papillomaviridae genetics, Papillomavirus Infections blood, Papillomavirus Infections diagnosis, Papillomavirus Infections pathology, Prevalence, Risk Factors, Specimen Handling methods, Specimen Handling statistics & numerical data, Uterine Cervical Neoplasms diagnosis, Uterine Cervical Neoplasms virology, Vagina pathology, Vagina virology, Young Adult, Early Detection of Cancer methods, Mass Screening methods, Papillomaviridae isolation & purification, Papillomavirus Infections epidemiology, Patient Acceptance of Health Care statistics & numerical data, Uterine Cervical Neoplasms prevention & control
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Objective: We evaluated acceptability of cervico-vaginal self-collection (CVSC) and prevalence of human papillomavirus (HPV) in Human immunodeficiency virus (HIV)-infected and HIV-uninfected women living in the Tapajós region, Amazon, Brazil., Methods: Cross-sectional study recruited 153 non-indigenous women (HIV-uninfected, n = 112 and HIV-infected, n = 41) who voluntarily sought assistance in health services. Peripheral blood for HIV screening and cervical scraping (CS) for HPV detection were collected. Women who accepted to perform CVSC received instructions and individual collection kits. Risk factors for high-risk HPV genotypes (hrHPV) were identified by uni- and multivariate analyses., Results: The overall acceptability of CVSC was 87%. Only HIV-infected women had cytological abnormalities (12.2%). Prevalence of any HPV and hrHPV infection was 42.9% and 47.9% for HIV-uninfected and 97.6% and 77.5% for HIV-infected women, respectively. There was significant agreement in the detection of HPV (88%, 0.76, 95% confidence interval [CI], 0.65-0.87) and hrHPV (79.7%, 0.56, 95% CI, 0.41-0.71) between self-collected and clinician-collected samples. The most prevalent hrHPV types were HPV16 and HPV18 in HIV-uninfected and HPV16, HPV51 and HPV59 in HIV-infected women. HIV-infected women with hrHPV infection had multiple hrHPV infections (p = 0.005) and lower CD4 count (p = 0.018). Risk factors for hrHPV infection included being HIV-infected and having five or more sexual partners., Conclusions: CVSC had high acceptability and high prevalence of hrHPV types in women living in the Tapajós region, Amazon, Brazil., (Copyright © 2018 Elsevier Inc. All rights reserved.)
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- 2018
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32. Human Immunodeficiency Virus Antiretroviral Resistance and Transmission in Mother-Infant Pairs Enrolled in a Large Perinatal Study.
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Yeganeh N, Kerin T, Ank B, Watts DH, Camarca M, Joao EC, Pilotto JH, Veloso VG, Bryson Y, Gray G, Theron G, Dickover R, Morgado MG, Santos B, Kreitchmann R, Mofenson L, and Nielsen-Saines K
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- Adolescent, Adult, Anti-HIV Agents classification, Female, HIV Infections transmission, HIV-1 genetics, Humans, Infant, Mutation, Pregnancy, Young Adult, Anti-HIV Agents pharmacology, Drug Resistance, Multiple, Viral, HIV Infections virology, HIV-1 drug effects, Infectious Disease Transmission, Vertical
- Abstract
Background: The presence of antiretroviral drug-associated resistance mutations (DRMs) may be particularly problematic in human immunodeficiency virus (HIV)-infected pregnant women as it can lead to mother-to-child transmission (MTCT) of resistant HIV strains. This study evaluated the prevalence and the effect of antiretroviral DRMs in previously untreated mother-infant pairs., Methods: A case-control design of 1:4 (1 transmitter to 4 nontransmitters) was utilized to evaluate DRMs as a predictor of HIV MTCT in specimens obtained from mother-infant pairs. ViroSeq HIV-1 genotyping was performed on mother-infant specimens to assess for clinically relevant DRMs., Results: One hundred forty infants acquired HIV infection; of these, 123 mother-infant pairs (88%) had specimens successfully amplified using ViroSeq and assessed for drug resistance genotyping. Additionally, 483 of 560 (86%) women who did not transmit HIV to infants also had samples evaluated for DRMs. Sixty-three of 606 (10%) women had clinically relevant DRMs; 12 (2%) had DRMs against >1 drug class. Among 123 HIV-infected infants, 13 (11%) had clinically relevant DRMs, with 3 (2%) harboring DRMs against >1 drug class. In univariate and multivariate analyses, DRMs in mothers were not associated with increased HIV MTCT (adjusted odds ratio, 0.8 [95% confidence interval, .4-1.5]). Presence of DRMs in transmitting mothers was strongly associated with DRM presence in their infants (P < .001)., Conclusions: Preexisting DRMs were common in untreated HIV-infected pregnant women, but did not increase the risk of HIV MTCT. However, if women with DRMs are not virologically suppressed, they may transmit resistant mutations, thus complicating infant management.
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- 2018
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33. HIV Drug Resistance in Adults Receiving Early vs. Delayed Antiretroviral Therapy: HPTN 052.
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Palumbo PJ, Fogel JM, Hudelson SE, Wilson EA, Hart S, Hovind L, Piwowar-Manning E, Wallis C, Papathanasopoulos MA, Morgado MG, Saravanan S, Tripathy S, Eron JJ, Gallant JE, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Pilotto JH, Kumwenda J, Akelo V, Godbole SV, Santos BR, Grinsztejn B, Panchia R, Chariyalertsak S, Makhema J, Badal-Faesen S, Chen YQ, Cohen MS, and Eshleman SH
- Subjects
- Adult, Anti-Retroviral Agents administration & dosage, Antiretroviral Therapy, Highly Active methods, Clinical Trials as Topic, Female, Genotype, Humans, Male, Microbial Sensitivity Tests, Treatment Failure, Viral Load, Anti-Retroviral Agents pharmacology, Drug Resistance, Viral, HIV drug effects, HIV Infections drug therapy, HIV Infections virology, Secondary Prevention, Time-to-Treatment
- Abstract
Introduction: We evaluated HIV drug resistance in adults who received early vs. delayed antiretroviral therapy (ART) in a multinational trial [HIV Prevention Trials Network (HPTN) 052, enrollment 2005-2010]. In HPTN 052, 1763 index participants were randomized to start ART at a CD4 cell count of 350-550 cells/mm (early ART arm) or <250 cells/mm (delayed ART arm). In May 2011, interim study results showed benefit of early ART, and all participants were offered ART regardless of CD4 cell count; the study ended in 2015., Methods: Virologic failure was defined as 2 consecutive viral loads >1000 copies/mL >24 weeks after ART initiation. Drug resistance testing was performed for pretreatment (baseline) and failure samples from participants with virologic failure., Results: HIV genotyping results were obtained for 211/249 participants (128 early ART arm and 83 delayed ART arm) with virologic failure. Drug resistance was detected in 4.7% of participants at baseline; 35.5% had new resistance at failure. In univariate analysis, the frequency of new resistance at failure was lower among participants in the early ART arm (compared with delayed ART arm, P = 0.06; compared with delayed ART arm with ART initiation before May 2011, P = 0.032). In multivariate analysis, higher baseline viral load (P = 0.0008) and ART regimen (efavirenz/lamivudine/zidovudine compared with other regimens, P = 0.024) were independently associated with higher risk of new resistance at failure., Conclusions: In HPTN 052, the frequency of new drug resistance at virologic failure was lower in adults with early ART initiation. The main factor associated with reduced drug resistance with early ART was lower baseline viral load.
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- 2018
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34. Prevalence of asymptomatic urethritis by Chlamydia trachomatis and Neisseria gonorrhoeae and associated risk factors among males living with HIV-1.
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Silva GARD, Motta HLSN, Souza EFA, Cardoso PANM, Pilotto JH, Eyer-Silva WA, Ribeiro LCP, Santos MSD, Azevedo MCVM, Pinto JFDC, Motta RN, and Ferry FRA
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- AIDS-Related Opportunistic Infections diagnosis, AIDS-Related Opportunistic Infections microbiology, Adolescent, Adult, Brazil epidemiology, Chlamydia Infections diagnosis, Chlamydia trachomatis isolation & purification, Cross-Sectional Studies, Gonorrhea diagnosis, Humans, Male, Middle Aged, Neisseria gonorrhoeae isolation & purification, Risk Factors, Urethritis diagnosis, Urethritis microbiology, AIDS-Related Opportunistic Infections epidemiology, Asymptomatic Infections epidemiology, Chlamydia Infections epidemiology, Gonorrhea epidemiology, Urethritis epidemiology
- Abstract
Objectives: The increase in HIV transmissibility in non-ulcerative sexually transmitted infection is already well-established. It is estimated that symptomatic carriers of N. gonorrhoeae and C. trachomatis have a relative risk of 4.8-fold and 3.6-fold, respectively, for the sexual acquisition of HIV. This type of evaluation for asymptomatic urethritis is necessary to reinforce strategies to combat HIV transmission. This study aims to assess the prevalence of patients with asymptomatic urethritis among men diagnosed with HIV-1 and determine the risk factors associated with this infection., Methods: We enrolled a total of 115 male patients aged 18 years or older who have been diagnosed with HIV infection and have no symptoms of urethritis or other sexually transmitted infections and who have been evaluated between May and August 2015 in a follow-up visit at the Immunology Outpatient Clinic of a Brazilian University Hospital., Results: Four asymptomatic patients were positive for C. trachomatis and were considered asymptomatic carriers of urethritis. Prevalence was 3.47%. Patients who were positive for C. trachomatis urethritis had a lower mean age (p = 0.015)., Conclusion: The presence of asymptomatic sexually transmitted infection is a challenge in clinical practice. We recommend that, in outpatient practice, the habit of inquiring on previous sexual behavior to obtain more information about risks and associations with asymptomatic sexually transmitted infection, a routine physical examination and complementary tests to detect STI pathogens should be performed to discard these conditions. The development of rapid tests for this purpose should also be encouraged.
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- 2018
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35. Co-infection of human herpesvirus type 2 (HHV-2) and human immunodeficiency virus (HIV) among pregnant women in Rio de Janeiro, Brazil.
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Lima LRP, Fernandes LEBC, Villela DAM, Morgado MG, Pilotto JH, and de Paula VS
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- Adult, Antibodies, Viral blood, Brazil epidemiology, Enzyme-Linked Immunosorbent Assay, Female, HIV Infections epidemiology, Herpes Genitalis epidemiology, Humans, Polymerase Chain Reaction, Pregnancy, Pregnancy Complications, Infectious epidemiology, Pregnant Women, Prevalence, Young Adult, Coinfection epidemiology, HIV, HIV Infections diagnosis, Herpes Genitalis diagnosis, Herpesvirus 2, Human isolation & purification, Pregnancy Complications, Infectious virology
- Abstract
Pregnant women who are infected with the Human Immunodeficiency Virus (HIV) are particularly vulnerable to severe and recurrent infections with Human Herpesvirus 2 (HHV-2). Neonatal transmission of HHV-2 has been associated with malformations and neurological sequelae in infants, which makes it very important to perform antenatal monitoring for genital herpes. In the study, 134 pregnant women infected with HIV were tested for HHV-2 IgM and IgG using an enzyme-linked immunosorbent assay (ELISA) and had HHV-2 DNA analyzed by Real Time Polymerase Chain Reaction (qPCR). Fisher's exact test was applied to analyze the epidemiological dates (p < 0.05). A total of 59.7% of the pregnant women infected with HIV had HHV-2 IgG and 3.75% of them showed HHV-2 viremia. HHV-2 IgM was found in 6% of the pregnant women and 25% of them had HHV-2 viremia. The risk factors associated with HHV-2 seropositive were age under 20 and a CD4/CD8 ratio > 1. Our study found high HHV-2/HIV coinfection prevalence and HHV-2 viremia among patients with recurrent and primary genital infection, reinforcing the need of prevention and control of HHV-2 infection in order to avoid this virus transmission.
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- 2018
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36. Combined evaluation of sexually transmitted infections in HIV-infected pregnant women and infant HIV transmission.
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Adachi K, Xu J, Yeganeh N, Camarca M, Morgado MG, Watts DH, Mofenson LM, Veloso VG, Pilotto JH, Joao E, Gray G, Theron G, Santos B, Fonseca R, Kreitchmann R, Pinto J, Mussi-Pinhata MM, Ceriotto M, Machado DM, Bryson YJ, Grinsztejn B, Moye J, Klausner JD, Bristow CC, Dickover R, Mirochnick M, and Nielsen-Saines K
- Subjects
- Adolescent, Adult, Chlamydia Infections complications, Chlamydia trachomatis, Cross-Sectional Studies, Female, Gonorrhea complications, Humans, Infant, Infant, Newborn, Middle Aged, Pregnancy, Retrospective Studies, Risk Factors, Syphilis complications, Young Adult, HIV Infections complications, HIV Infections transmission, Infectious Disease Transmission, Vertical, Pregnancy Complications, Infectious, Sexually Transmitted Diseases complications
- Abstract
Background: Sexually transmitted infections (STIs) including Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (TP), and cytomegalovirus (CMV) may lead to adverse pregnancy and infant outcomes. The role of combined maternal STIs in HIV mother-to-child transmission (MTCT) was evaluated in mother-infant pairs from NICHD HPTN 040., Methodology: Urine samples from HIV-infected pregnant women during labor were tested by polymerase chain reaction (PCR) for CT, NG, and CMV. Infant HIV infection was determined by serial HIV DNA PCR testing. Maternal syphilis was tested by VDRL and confirmatory treponemal antibodies., Results: A total of 899 mother-infant pairs were evaluated. Over 30% had at least one of the following infections (TP, CT, NG, and/or CMV) detected at the time of delivery. High rates of TP (8.7%), CT (17.8%), NG (4%), and CMV (6.3%) were observed. HIV MTCT was 9.1% (n = 82 infants). HIV MTCT was 12.5%, 10.3%, 11.1%, and 26.3% among infants born to women with CT, TP, NG or CMV respectively. Forty-two percent of HIV-infected infants were born to women with at least one of these 4 infections. Women with these infections were nearly twice as likely to have an HIV-infected infant (aOR 1.9, 95% CI 1.1-3.0), particularly those with 2 STIs (aOR 3.4, 95% CI 1.5-7.7). Individually, maternal CMV (aOR 4.4 1.5-13.0) and infant congenital CMV (OR 4.1, 95% CI 2.2-7.8) but not other STIs (TP, CT, or NG) were associated with an increased risk of HIV MTCT., Conclusion: HIV-infected pregnant women identified during labor are at high risk for STIs. Co-infection with STIs including CMV nearly doubles HIV MTCT risk. CMV infection appears to confer the largest risk of HIV MTCT., Trial Registration: NCT00099359.
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- 2018
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37. Detection of occult hepatitis B in serum and oral fluid samples.
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Portilho MM, Nabuco LC, Villela-Nogueira CA, Brandão-Mello CE, Pilotto JH, Flores GL, Lewis-Ximenez LL, Lampe E, and Villar LM
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- Adult, Aged, DNA, Viral blood, Female, Hepatitis B virus isolation & purification, Humans, Male, Middle Aged, Polymerase Chain Reaction, Viral Load, DNA, Viral analysis, Hepatitis B diagnosis, Hepatitis B Antibodies analysis, Hepatitis B Surface Antigens analysis, Hepatitis B virus genetics, Saliva virology
- Abstract
In occult hepatitis B infection (OBI), hepatitis B virus DNA (HBV DNA) can be detected in serum samples; however, oral fluid collection for detection of HBV DNA has not yet been explored, despite the availability of collection devices. Serum and oral fluid samples from 45 hepatitis B core antibody (anti-HBc)-positive patients were collected for the amplification of the HBV polymerase gene. HBV DNA was detected in five serum and four oral fluid samples (the detection limit for oral fluid was 1.656 log IU/mL in paired serum). In conclusion, simple methodologies of sample collection and in-house polymerase chain reaction (PCR) allowed detection of HBV DNA, and these could be used to improve the diagnosis of OBI, especially in locations with limited resources.
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- 2018
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38. Comparison of Hepatitis B Virus Infection in HIV-Infected and HIV-Uninfected Participants Enrolled in a Multinational Clinical Trial: HPTN 052.
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Greer AE, Ou SS, Wilson E, Piwowar-Manning E, Forman MS, McCauley M, Gamble T, Ruangyuttikarn C, Hosseinipour MC, Kumarasamy N, Nyirenda M, Grinsztejn B, Pilotto JH, Kosashunhanan N, Gonçalves de Melo M, Makhema J, Akelo V, Panchia R, Badal-Faesen S, Chen YQ, Cohen MS, Eshleman SH, Thio CL, and Valsamakis A
- Subjects
- Adult, Africa epidemiology, Alanine Transaminase blood, Aspartate Aminotransferases blood, Brazil epidemiology, CD4 Lymphocyte Count, Female, HIV Infections blood, HIV Infections virology, Hepatitis B blood, Hepatitis B Surface Antigens blood, Humans, India epidemiology, Male, Prevalence, Thailand epidemiology, Viral Load, Coinfection epidemiology, Coinfection virology, HIV Infections epidemiology, Hepatitis B epidemiology, Hepatitis B virology, Hepatitis B virus pathogenicity
- Abstract
Objective: Data comparing hepatitis B virus (HBV) infection in HIV-infected [HIV(+)], and HIV-uninfected [HIV(-)] individuals recruited into the same study are limited. HBV infection status and chronic hepatitis B (cHB) were characterized in a multinational clinical trial: HIV Prevention Trials Network (HPTN 052)., Method: HBV infection status at enrollment was compared between HIV(+) (N = 1241) and HIV(-) (N = 1232) from 7 HBV-endemic countries. Hepatitis B e antigen and plasma HBV DNA were determined in cHB. Median CD4, median plasma HIV RNA, and prevalence of transaminase elevation were compared in HIV(+) with and without cHB. Significance was assessed with χ, Fisher exact, and median tests., Results: Among all participants, 33.6% had HBV exposure without cHB (8.9% isolated HBV core antibody, "HBcAb"; 24.7% HBcAb and anti-HB surface antibody positive, "recovered"), 4.3% had cHB, 8.9% were vaccinated, and 53.5% were uninfected. Data were similar among HIV(+) and HIV(-) except for isolated HBcAb, which was more prevalent in HIV(+) than HIV(-) [10.1% vs. 7.7%, P = 0.046]. Median HBV DNA trended higher in HIV(+) than in HIV(-). In HIV(+) with cHB versus those without cHB, transaminase elevations were more prevalent (alanine aminotransferase ≤ grade 2, 12% vs. 5.2%, P = 0.037; aspartate aminotransferase ≤ grade 2, 26% vs. 6.0%, P < 0.001), CD4 trended lower, and HIV RNA was similar., Conclusions: HBV infection status did not differ by HIV infection status. HIV co-infection was associated with isolated HBcAb and a trend of increased HBV DNA. In HIV, cHB was associated with mild transaminase elevations and a trend toward lower CD4.
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- 2017
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39. Performance of rapid diagnostic tests for detection of Hepatitis B and C markers in HIV infected patients.
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Barbosa JR, Colares JKB, Flores GL, Cortes VF, Miguel JC, Portilho MM, Marques VA, Potsch DV, Brandão-Mello CE, Amendola-Pires M, Pilotto JH, Lima DM, Lampe E, and Villar LM
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- Adult, Aged, Aged, 80 and over, Biomarkers blood, Brazil epidemiology, Female, HIV Infections epidemiology, HIV Infections virology, Hepacivirus immunology, Hepacivirus isolation & purification, Hepatitis B complications, Hepatitis B epidemiology, Hepatitis B immunology, Hepatitis B Surface Antigens blood, Hepatitis B Surface Antigens immunology, Hepatitis B virus immunology, Hepatitis B virus isolation & purification, Hepatitis C complications, Hepatitis C epidemiology, Hepatitis C immunology, Hepatitis C Antibodies blood, Hepatitis C Antibodies immunology, Humans, Immunoenzyme Techniques methods, Male, Middle Aged, Sensitivity and Specificity, Viral Load, HIV Infections complications, Hepatitis B diagnosis, Hepatitis C diagnosis, Serologic Tests
- Abstract
There is little information describing the influence of HIV infection upon the performance of rapid diagnostic tests (RDTs) for hepatitis B and C virus diagnosis. This study aims to evaluate the performance of RDTs for HBsAg and anti-HCV detection among HIV-infected individuals. A total of 362 HIV infected individuals were recruited from clinics between January 2013 to November 2014 in the southeast and northeast of Brazil. HBsAg and anti-HCV were detected using commercial EIAs and four RDTs: HBV (Vikia HBsAg
® and Wama Imuno-Rapido HBV® ) and HCV (Bioeasy Teste Rápido HCV® and Wama Imuno-Rapido HCV® ). Reactive HBsAg and anti-HCV serum samples were tested for HBV DNA and HCV RNA. Sensitivity, specificity and kappa statistic were determined. Using EIA, HBsAg and anti-HCV were detected in 14 (3.9%) and 37 (10.2%) serum samples respectively. Using serum only, HBsAg RDTs demonstrated sensitivities and specificities above 92.0% and Kappa values above 89.0%. Anti-HCV RDTs demonstrated sensitivity and specificities above 82.0% and Kappa higher than 89.0%. Using whole blood samples, Vikia HBsAg® and Wama Imuno-Rapido HCV® showed sensitivity and specificity above 99.0% with Kappa of 66.4% and 100%, respectively. HIV viral load was higher among discordant results for anti-HCV RDT. RDTs demonstrated good performance in HIV infected individuals showing the usefulness of assays in this population., (Copyright © 2017 Elsevier B.V. All rights reserved.)- Published
- 2017
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40. Maternal Zika Virus Disease Severity, Virus Load, Prior Dengue Antibodies, and Their Relationship to Birth Outcomes.
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Halai UA, Nielsen-Saines K, Moreira ML, de Sequeira PC, Junior JPP, de Araujo Zin A, Cherry J, Gabaglia CR, Gaw SL, Adachi K, Tsui I, Pilotto JH, Nogueira RR, de Filippis AMB, and Brasil P
- Subjects
- Adolescent, Adult, Antibodies, Viral blood, Brain abnormalities, Brain diagnostic imaging, Brazil epidemiology, Dengue Virus immunology, Female, Humans, Live Birth epidemiology, Middle Aged, Nervous System Diseases congenital, Nervous System Diseases diagnosis, Nervous System Diseases physiopathology, Nervous System Malformations diagnosis, Neuroimaging, Neurologic Examination, Pregnancy, Pregnancy Complications, Infectious virology, Prospective Studies, RNA, Viral blood, Severity of Illness Index, Viral Load, Young Adult, Zika Virus genetics, Fetal Death, Nervous System Diseases epidemiology, Nervous System Malformations epidemiology, Pregnancy Complications, Infectious blood, Zika Virus Infection blood, Zika Virus Infection complications
- Abstract
Background: Congenital Zika virus (ZIKV) syndrome is a newly identified condition resulting from infection during pregnancy. We analyzed outcome data from a mother-infant cohort in Rio de Janeiro in order to assess whether clinical severity of maternal ZIKV infection was associated with maternal virus load, prior dengue antibodies, or abnormal pregnancy/infant outcomes., Methods: A clinical severity assessment tool was developed based on duration of fever, severity of rash, multisystem involvement, and duration of symptoms during ZIKV infection. ZIKV-RNA load was quantified by polymerase chain reaction (PCR) cycles in blood/ urine. Dengue immunoglobulin G (IgG) antibodies were measured at baseline. Adverse outcomes were defined as fetal loss or a live infant with grossly abnormal clinical or brain imaging findings. Regression models were used to study potential associations., Results: 131 ZIKV-PCR positive pregnant women were scored for clinical disease severity, 6 (4.6%) had mild disease, 98 (74.8%) had moderate disease, and 27 (20.6%) severe manifestations of ZIKV infection. There were 58 (46.4%) abnormal outcomes with 9 fetal losses (7.2%) in 125 pregnancies. No associations were found between: disease severity and abnormal outcomes (P = .961; odds ratio [OR]: 1.00; 95% confidence interval [CI]: 0.796-1.270); disease severity and viral load (P = .994); viral load and adverse outcomes (P = .667; OR: 1.02; 95% CI: 0.922-1.135); or existence of prior dengue antibodies (88% subjects) with severity score, ZIKV-RNA load or adverse outcomes (P = .667; OR: 0.78; 95% CI: 0.255-2.397)., Conclusions: Congenital ZIKV syndrome does not appear to be associated with maternal disease severity, ZIKV-RNA load at time of infection or existence of prior dengue antibodies., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
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- 2017
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41. Evaluation of HBsAg and anti-HBc assays in saliva and dried blood spot samples according HIV status.
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Flores GL, Cruz HM, Potsch DV, May SB, Brandão-Mello CE, Pires MMA, Pilotto JH, Lewis-Ximenez LL, Lampe E, and Villar LM
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- Desiccation, HIV Infections complications, Humans, Immunoenzyme Techniques, Sensitivity and Specificity, Specimen Handling methods, Blood virology, Hepatitis B diagnosis, Hepatitis B Antibodies analysis, Hepatitis B Antibodies blood, Hepatitis B Surface Antigens analysis, Hepatitis B Surface Antigens blood, Saliva virology
- Abstract
Influence of HIV status in HBV markers detection in saliva and dried blood spots (DBS) was not well established. This study aims to evaluate the performance of optimized commercial immunoassay for identifying HBsAg and anti-HBc in saliva and DBS according HIV status. A sum of 535 individuals grouped as HIV
+ , HBV+ , HIV/HBV+ and HIV/HBV- were recruited where 347 and 188 were included for HBsAg and anti-HBc evaluation, respectively. Serum, DBS collected in Whatman 903 paper and saliva obtained using salivette device were analyzed using EIA. Increased sample volume and ROC curve analysis for cut off determination were used for DBS and saliva testing. HBsAg detection in saliva and DBS exhibited sensitivities of 80.9% and 85.6% and specificities of 86.8% and 96.3%. Sensitivity of anti-HBc in saliva and DBS were 82.4% and 76.9% and specificities in saliva and DBS were 96.9% and 91.7%. Low sensitivities were observed for HBsAg (62%) and anti-HBc (47%) detection in saliva of HIV/HBV+ individuals. OD values were also lower for HBsAg detection in DBS and saliva of HIV/HBV+ individuals compared to their serum samples. Statistical significance was found for sensitivities in HBsAg detection between saliva and DBS demonstrating high sensitivity for DBS specimens. In conclusion, HIV status or antiretroviral treatment appears to interfere in the performance of HBsAg and anti-HBc detection in DBS and saliva samples using the adapted commercial EIA., (Copyright © 2017 Elsevier B.V. All rights reserved.)- Published
- 2017
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42. Performance of ANTI-HCV testing in dried blood spots and saliva according to HIV status.
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Flores GL, Cruz HM, Marques VA, Villela-Nogueira CA, Potsch DV, May SB, Brandão-Mello CE, Pires MMA, Pilotto JH, Pollo-Flores P, Esberard EBC, Ivantes C, Lewis-Ximenez LL, Lampe E, and Villar LM
- Subjects
- Adult, Aged, CD4 Lymphocyte Count, Desiccation, Female, Humans, Male, Middle Aged, Sensitivity and Specificity, Specimen Handling methods, Surveys and Questionnaires, Viral Load, Blood immunology, Enzyme-Linked Immunosorbent Assay methods, HIV Infections complications, Hepatitis C diagnosis, Hepatitis C Antibodies analysis, Hepatitis C Antibodies blood, Saliva immunology
- Abstract
The use of saliva and dried blood spots (DBS) could increase access to HCV diagnosis for high-risk populations, such as HIV-infected individuals, but the performance of these assays has not been well established in this group. This study aims to evaluate HIV status, particularly TCD4
+ cell count and viral load, in the performance of anti-HCV testing using DBS and saliva. A total of 961 individuals classified as HCV+, HIV+, or HIV/HCV+, as well as negative controls, donated serum, DBS, and saliva samples for anti-HCV testing using a commercial enzyme immunoassay. Sample volume was modified for DBS and saliva, and an ROC curve was used for cut-off determination in saliva. Anti-HCV sensitivities were greater than 93% using DBS and saliva in the HCV+ group, while they were 83.3% and 95.6% for HCV/HIV+ individuals for DBS and saliva assays, respectively. Specificity varied from 91.7% to 100% using saliva and DBS in HIV monoinfected and control subjects. When only anti-HCV/HCV RNA+ serum samples, that is, true positives, were considered, the sensitivities were 98.3% and 100% for DBS and saliva, respectively, in the HCV+ group and 91.6% and 94.8% for DBS and saliva, respectively, in the HIV/HCV+ group. High absorbance values were observed among those presenting with HCV RNA in serum and low HIV viral load (less than 50 copies/mL). In conclusion, DBS and saliva samples could be used for anti-HCV detection, particularly to identify active HCV cases, but low sensitivity was observed for anti-HCV testing using DBS in the HIV/HCV+ group., (© 2017 Wiley Periodicals, Inc.)- Published
- 2017
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43. Cytomegalovirus Urinary Shedding in HIV-infected Pregnant Women and Congenital Cytomegalovirus Infection.
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Adachi K, Xu J, Ank B, Watts DH, Mofenson LM, Pilotto JH, Joao E, Santos B, Fonseca R, Kreitchmann R, Pinto J, Mussi-Pinhata MM, Gray G, Theron G, Morgado MG, Bryson YJ, Veloso VG, Klausner JD, Moye J, and Nielsen-Saines K
- Subjects
- Adolescent, Adult, DNA, Viral genetics, Female, Humans, Infant, Newborn, Predictive Value of Tests, Pregnancy, Prevalence, Real-Time Polymerase Chain Reaction, Retrospective Studies, Risk Factors, Viral Load, Virus Shedding, Young Adult, Cytomegalovirus genetics, Cytomegalovirus isolation & purification, Cytomegalovirus Infections complications, Cytomegalovirus Infections congenital, Cytomegalovirus Infections urine, Cytomegalovirus Infections virology, DNA, Viral urine, HIV Infections complications, Pregnancy Complications, Infectious urine, Pregnancy Complications, Infectious virology
- Abstract
Background: Cytomegalovirus (CMV) urinary shedding in pregnant women infected with human immunodeficiency virus (HIV) was evaluated to determine whether it poses an increased risk for congenital CMV infection (cCMV)., Methods: A subset of mother-infant pairs enrolled in the perinatal NICHD HPTN 040 study (distinguished by no antiretroviral use before labor) was evaluated. Maternal and infant urines were tested by qualitative real-time polymerase chain reaction (RT-PCR) for CMV DNA with quantitative RT-PCR performed on positive specimens., Results: Urine specimens were available for 260 women with 85.4% from the Americas and 14.6% from South Africa. Twenty-four women (9.2%) had detectable CMV viruria by qualitative PCR. Maternal CMV viruria was not associated with mean CD4 cell counts or HIV viral load but was associated with younger maternal age (P = .02). Overall, 10 of 260 infants (3.8%) had cCMV. Women with detectable peripartum CMV viruria were more likely to have infants with cCMV than those without: 20.8% (5/24) versus 2.1% (5/236), (P = .0001). Women with CMV viruria had significantly higher rates of HIV perinatal transmission (29.2% vs. 8.1%, P = .002). They were 5 times (adjusted odds ratio [aOR] = 5.6, 95% confidence interval [CI] 1.9-16.8) and nearly 30 times (aOR, 29.7; 95% CI, 5.4-164.2) more likely to transmit HIV and CMV to their infants, respectively. Maternal gonorrhea (aOR, 19.5; 95% CI, 2.5-151.3) and higher maternal HIV log10 viral load (OR, 2.8; 95% CI, 1.3-6.3) were also significant risk factors for cCMV., Conclusion: In this cohort of HIV-infected pregnant women not on antiretrovirals, urinary CMV shedding was a significant risk factor for CMV and HIV transmission to infants., Clinical Trials Registration Number: NCT00099359., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com)
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- 2017
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44. Association of HIV diversity and virologic outcomes in early antiretroviral treatment: HPTN 052.
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Palumbo PJ, Wilson EA, Piwowar-Manning E, McCauley M, Gamble T, Kumwenda N, Makhema J, Kumarasamy N, Chariyalertsak S, Hakim JG, Hosseinipour MC, Melo MG, Godbole SV, Pilotto JH, Grinsztejn B, Panchia R, Chen YQ, Cohen MS, Eshleman SH, and Fogel JM
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- CD4 Lymphocyte Count, Child, Cohort Studies, Female, HIV Infections virology, Humans, Male, Treatment Outcome, Viral Load, Anti-HIV Agents therapeutic use, HIV classification, HIV Infections drug therapy
- Abstract
Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral treatment (ART). We examined the association of HIV diversity with virologic outcomes in adults from the HPTN 052 trial who initiated ART at CD4 cell counts of 350-550 cells/mm3. A high resolution melting (HRM) assay was used to analyze baseline (pre-treatment) HIV diversity in six regions in the HIV genome (two in gag, one in pol, and three in env) from 95 participants who failed ART. We analyzed the association of HIV diversity in each genomic region with baseline (pre-treatment) factors and three clinical outcomes: time to virologic suppression after ART initiation, time to ART failure, and emergence of HIV drug resistance at ART failure. After correcting for multiple comparisons, we did not find any association of baseline HIV diversity with demographic, laboratory, or clinical characteristics. For the 18 analyses performed for clinical outcomes evaluated, there was only one significant association: higher baseline HIV diversity in one of the three HIV env regions was associated with longer time to ART failure (p = 0.008). The HRM diversity assay may be useful in future studies exploring the relationship between HIV diversity and clinical outcomes in individuals with HIV infection.
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- 2017
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45. Virologic outcomes in early antiretroviral treatment: HPTN 052.
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Eshleman SH, Wilson EA, Zhang XC, Ou SS, Piwowar-Manning E, Eron JJ, McCauley M, Gamble T, Gallant JE, Hosseinipour MC, Kumarasamy N, Hakim JG, Kalonga B, Pilotto JH, Grinsztejn B, Godbole SV, Chotirosniramit N, Santos BR, Shava E, Mills LA, Panchia R, Mwelase N, Mayer KH, Chen YQ, Cohen MS, and Fogel JM
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- Adult, Africa, Asia, Cohort Studies, Female, Humans, Male, Treatment Outcome, Anti-Retroviral Agents therapeutic use, HIV Infections drug therapy, Secondary Prevention, Viral Load
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Introduction: The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early antiretroviral therapy (ART) prevented 93% of HIV transmission events in serodiscordant couples. Some linked infections were observed shortly after ART initiation or after virologic failure., Objective: To evaluate factors associated with time to viral suppression and virologic failure in participants who initiated ART in HPTN 052., Methods: 1566 participants who had a viral load (VL) > 400 copies/mL at enrollment were included in the analyses. This included 832 in the early ART arm (CD4 350-550 cells/mm
3 at ART initiation) and 734 in the delayed ART arm (204 with a CD4 < 250 cells/mm3 at ART initiation; 530 with any CD4 at ART initiation). Viral suppression was defined as two consecutive VLs ≤ 400 copies/mL after ART initiation; virologic failure was defined as two consecutive VLs > 1000 copies/mL > 24 weeks after ART initiation., Results: Overall, 93% of participants achieved viral suppression by 12 months. The annual incidence of virologic failure was 3.6%. Virologic outcomes were similar in the two study arms. Longer time to viral suppression was associated with younger age, higher VL at ART initiation, and region (Africa vs. Asia). Virologic failure was strongly associated with younger age, lower educational level, and lack of suppression by three months; lower VL and higher CD4 at ART initiation were also associated with virologic failure., Conclusions: Several clinical and demographic factors were identified that were associated with longer time to viral suppression and virologic failure. Recognition of these factors may help optimize ART for HIV treatment and prevention.- Published
- 2017
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46. High HIV-1 Diversity and Prevalence of Transmitted Drug Resistance Among Antiretroviral-Naive HIV-Infected Pregnant Women from Rio de Janeiro, Brazil.
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Delatorre E, Silva-de-Jesus C, Couto-Fernandez JC, Pilotto JH, and Morgado MG
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- Adolescent, Adult, Anti-HIV Agents pharmacology, Brazil epidemiology, Female, Genotype, HIV Infections epidemiology, HIV Protease genetics, HIV Reverse Transcriptase genetics, HIV-1 isolation & purification, Humans, Pregnancy, Pregnancy Complications, Infectious epidemiology, Prevalence, Recombination, Genetic, Young Adult, Drug Resistance, Viral, Genetic Variation, HIV Infections virology, HIV-1 classification, HIV-1 genetics, Pregnancy Complications, Infectious virology
- Abstract
Antiretroviral (ARV) resistance mutations in human immunodeficiency virus type 1 (HIV-1) infection may reduce the efficacy of prophylactic therapy to prevent mother-to-child transmission (PMTCT) and future treatment options. This study evaluated the diversity and the prevalence of transmitted drug resistance (TDR) in protease (PR) and reverse transcriptase (RT) regions of HIV-1 pol gene among 87 ARV-naive HIV-1-infected pregnant women from Rio de Janeiro, Brazil, between 2012 and 2015. The viral diversity comprised HIV-1 subtypes B (67.8%), F1 (17.2%), and C (4.6%); the circulating recombinant forms 12_BF (2.3%), 28/29_BF, 39_BF, 02_AG (1.1% each) and unique recombinants forms (4.5%). The overall prevalence of any TDR was 17.2%, of which 5.7% for nucleoside RT inhibitors, 5.7% for non-nucleoside RT inhibitors, and 8% for PR inhibitors. The TDR prevalence found in this population may affect the virological outcome of the standard PMTCT ARV-regimens, reinforcing the importance of continuous monitoring.
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- 2017
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47. Zika Virus Infection in Pregnant Women in Rio de Janeiro.
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Brasil P, Pereira JP Jr, Moreira ME, Ribeiro Nogueira RM, Damasceno L, Wakimoto M, Rabello RS, Valderramos SG, Halai UA, Salles TS, Zin AA, Horovitz D, Daltro P, Boechat M, Raja Gabaglia C, Carvalho de Sequeira P, Pilotto JH, Medialdea-Carrera R, Cotrim da Cunha D, Abreu de Carvalho LM, Pone M, Machado Siqueira A, Calvet GA, Rodrigues Baião AE, Neves ES, Nassar de Carvalho PR, Hasue RH, Marschik PB, Einspieler C, Janzen C, Cherry JD, Bispo de Filippis AM, and Nielsen-Saines K
- Subjects
- Adolescent, Adult, Brain abnormalities, Brazil epidemiology, Central Nervous System embryology, Female, Fetal Growth Retardation epidemiology, Fetus abnormalities, Gestational Age, Humans, Middle Aged, Pregnancy, Premature Birth epidemiology, Ultrasonography, Prenatal, Young Adult, Central Nervous System abnormalities, Fetal Death etiology, Fetal Growth Retardation virology, Microcephaly virology, Pregnancy Complications, Infectious, Zika Virus isolation & purification, Zika Virus Infection complications
- Abstract
Background: Zika virus (ZIKV) has been linked to central nervous system malformations in fetuses. To characterize the spectrum of ZIKV disease in pregnant women and infants, we followed patients in Rio de Janeiro to describe clinical manifestations in mothers and repercussions of acute ZIKV infection in infants., Methods: We enrolled pregnant women in whom a rash had developed within the previous 5 days and tested blood and urine specimens for ZIKV by reverse-transcriptase-polymerase-chain-reaction assays. We followed women prospectively to obtain data on pregnancy and infant outcomes., Results: A total of 345 women were enrolled from September 2015 through May 2016; of these, 182 women (53%) tested positive for ZIKV in blood, urine, or both. The timing of acute ZIKV infection ranged from 6 to 39 weeks of gestation. Predominant maternal clinical features included a pruritic descending macular or maculopapular rash, arthralgias, conjunctival injection, and headache; 27% had fever (short-term and low-grade). By July 2016, a total of 134 ZIKV-affected pregnancies and 73 ZIKV-unaffected pregnancies had reached completion, with outcomes known for 125 ZIKV-affected and 61 ZIKV-unaffected pregnancies. Infection with chikungunya virus was identified in 42% of women without ZIKV infection versus 3% of women with ZIKV infection (P<0.001). Rates of fetal death were 7% in both groups; overall adverse outcomes were 46% among offspring of ZIKV-positive women versus 11.5% among offspring of ZIKV-negative women (P<0.001). Among 117 live infants born to 116 ZIKV-positive women, 42% were found to have grossly abnormal clinical or brain imaging findings or both, including 4 infants with microcephaly. Adverse outcomes were noted regardless of the trimester during which the women were infected with ZIKV (55% of pregnancies had adverse outcomes after maternal infection in the first trimester, 52% after infection in the second trimester, and 29% after infection in the third trimester)., Conclusions: Despite mild clinical symptoms in the mother, ZIKV infection during pregnancy is deleterious to the fetus and is associated with fetal death, fetal growth restriction, and a spectrum of central nervous system abnormalities. (Funded by Ministério da Saúde do Brasil and others.).
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- 2016
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48. Tracing the origin of a singular HIV-1 CRF45_cpx clade identified in Brazil.
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Delatorre E, de Azevedo SSD, Rodrigues-Pedro A, Velasco-de-Castro CA, Couto-Fernandez JC, Pilotto JH, and Morgado MG
- Subjects
- Bayes Theorem, Brazil epidemiology, Contact Tracing, Female, Genome, Viral genetics, HIV Infections epidemiology, Humans, Male, Phylogeny, Pregnancy, RNA, Viral analysis, RNA, Viral genetics, Sequence Alignment, Sequence Analysis, DNA, HIV Infections transmission, HIV Infections virology, HIV-1 classification, HIV-1 genetics
- Abstract
The HIV-1 epidemiology has changed over the past decade toward a marked increase in the circulation of strains previously restricted to local epidemics. Recent molecular epidemiological surveys identified some HIV-1 strains of probable African origin circulating in Brazil, including the Circulating Recombinant Form (CRF) 45_cpx, a complex A1/K/U recombinant that circulates in Central Africa. Here, we characterize partial genomic sequences and reconstruct the evolutionary history of HIV-1 CRF45_cpx-related recombinant samples identified in independent studies carried out with HIV+ individuals in Brazil. The sequences were obtained by overlapping PCR amplifications followed by direct sequencing. Recombination profiles were determined by phylogenetic and bootscaning analyses. The evolutionary history was estimated by a Bayesian coalescent-based method using datasets representing the gag, pol and env gene fragments. Six of the 10 samples isolated in Rio de Janeiro showed a CRF45_cpx-like pattern throughout the sequenced genome. The remaining were classified as second-generation recombinants, showing the mosaic patterns: CRF45_cpx/B/D/F1/U, CRF45_cpx/B/F1/U, CRF45_cpx/B/U and CRF45_cpx/F1. All Brazilian CRF45_cpx sequences, except one, formed a monophyletic clade (CRF45-BR), which seems to be the result of a single introduction event that has spread to the Rio de Janeiro, São Paulo and Minas Gerais states and is related to sequences from Argentina, Italy and Belgium. The Bayesian analyses pointed out quite consistent onset dates for CRF45-BR clade (~1984: 1976-1996) in the three gene datasets. These results indicate that the CRF45-BR clade has been circulating in the Southeastern Brazilian region for about 30years, although its presence was not detected until recently due to its very low prevalence. This reinforces the relevance of large-scale molecular surveillance data to identify the emergence of new HIV variants and their impact on local epidemics., (Copyright © 2016 Elsevier B.V. All rights reserved.)
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- 2016
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49. Antiretroviral Therapy for the Prevention of HIV-1 Transmission.
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Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Grinsztejn B, Pilotto JH, Godbole SV, Chariyalertsak S, Santos BR, Mayer KH, Hoffman IF, Eshleman SH, Piwowar-Manning E, Cottle L, Zhang XC, Makhema J, Mills LA, Panchia R, Faesen S, Eron J, Gallant J, Havlir D, Swindells S, Elharrar V, Burns D, Taha TE, Nielsen-Saines K, Celentano DD, Essex M, Hudelson SE, Redd AD, and Fleming TR
- Subjects
- Adult, Female, Follow-Up Studies, HIV Infections prevention & control, HIV Seropositivity, Humans, Intention to Treat Analysis, Kaplan-Meier Estimate, Male, Middle Aged, Risk, Young Adult, Anti-Retroviral Agents therapeutic use, Disease Transmission, Infectious prevention & control, HIV Infections transmission, HIV-1 genetics, Sexual Partners
- Abstract
Background: An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission., Methods: We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1-negative partner in an intention-to-treat analysis., Results: Index participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant., Conclusions: The early initiation of ART led to a sustained decrease in genetically linked HIV-1 infections in sexual partners. (Funded by the National Institute of Allergy and Infectious Diseases; HPTN 052 ClinicalTrials.gov number, NCT00074581 .).
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- 2016
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50. Chlamydia trachomatis and Neisseria gonorrhoeae in HIV-infected Pregnant Women and Adverse Infant Outcomes.
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Adachi K, Klausner JD, Xu J, Ank B, Bristow CC, Morgado MG, Watts DH, Weir F, Persing D, Mofenson LM, Veloso VG, Pilotto JH, Joao E, Gray G, Theron G, Santos B, Fonseca R, Kreitchmann R, Pinto J, Mussi-Pinhata MM, Ceriotto M, Machado DM, Bryson YJ, Grinsztejn B, Bastos FI, Siberry G, and Nielsen-Saines K
- Subjects
- Chlamydia Infections complications, Chlamydia trachomatis, Cohort Studies, Female, Gonorrhea complications, HIV Infections complications, Humans, Infant, Newborn, Neisseria gonorrhoeae, Pregnancy, Randomized Controlled Trials as Topic, Urine microbiology, Chlamydia Infections epidemiology, Gonorrhea epidemiology, HIV Infections epidemiology, Infectious Disease Transmission, Vertical statistics & numerical data, Pregnancy Complications, Infectious epidemiology
- Abstract
Background: Sexually transmitted infections (STIs) in pregnancy such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) may lead to adverse infant outcomes., Methods: Individual urine specimens from HIV-infected pregnant women diagnosed with HIV during labor were collected at the time of infant birth and tested by polymerase chain reaction for CT and NG. Infant HIV infection was determined at 3 months with morbidity/mortality assessed through 6 months., Results: Of 1373 maternal urine samples, 277 (20.2%) were positive for CT and/or NG; 249 (18.1%) for CT, 63 (4.6%) for NG and 35 (2.5%) for both CT and NG. HIV infection was diagnosed in 117 (8.5%) infants. Highest rates of adverse outcomes (sepsis, pneumonia, congenital syphilis, septic arthritis, conjunctivitis, low birth weight, preterm delivery and death) were noted in infants of women with CT and NG (23/35, 65.7%) compared with NG (16/28, 57.1%), CT (84/214, 39.3%) and no STI (405/1096, 37%, P = 0.001). Death (11.4% vs. 3%, P = 0.02), low birth weight (42.9% vs. 16.9%, P = 0.001) and preterm delivery (28.6% vs. 10.2%, P = 0.008) were higher among infants of CT and NG-coinfected women. Infants who had any adverse outcome and were born to women with CT and/or NG were 3.5 times more likely to be HIV infected after controlling for maternal syphilis (odds ratio: 3.5, 95% confidence interval: 1.4-8.3). By adjusted multivariate logistic regression, infants born to mothers with any CT and/or NG were 1.35 times more likely to have an adverse outcome (odds ratio, 1.35; 95% confidence interval, 1.03-1.76)., Conclusions: STIs in HIV-infected pregnant women are associated with adverse outcomes in HIV-exposed infected and uninfected infants.
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- 2016
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