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HIV-negative individuals in serodiscordant partnerships experience reduced risk of HIV acquisition when their partners adhere to ART and achieve undetectable viral loads. Partnership support may encourage ART adherence, reducing viral load and the risk of HIV transmission. This study aims to determine whether HIV viral suppression is associated with partnership status and partnership support among 201 HIV positive (HIV+ individuals in serodiscordant partnerships and 100 HIV+ unpartnered individuals receiving care at Hospital Nossa Senhora da Conceição in Porto Alegre, Brazil between 2014 and 2016. Clinical data and patient-reported questionnaire data were assessed, and propensity scores were used to control for confounding variables in adjusted logistic regression models. Viral suppression did not significantly differ between HIV+ partnered (78.5% virally suppressed) and unpartnered (76.0% virally suppressed) individuals. Among individuals in partnerships, viral suppression was significantly associated with having a partner who attended monthly clinic visits (AOR 2.99; 95% CI 1.00–8.93). Instrumental social support—attending monthly visits—may improve the odds of viral suppression among HIV+ individuals in serodiscordant relationships. Supplementary Information The online version of this article (10.1007/s10461-020-03124-5) contains supplementary material, which is available to authorized users.

Chronic liver disease is an important cause of morbidity and mortality among people living with human immunodeficiency virus (HIV) and is frequently related to non-alcoholic fatty liver disease (NAFLD). The objective is to estimate the prevalence and risk factors of hepatic steatosis among consecutive patients with stable HIV infection on antiretroviral therapy (ART). Also, the use of transient elastography (TE) as a mean to identify a subgroup at risk for non-alcoholic steatohepatitis (NASH) and/or liver fibrosis. HIV infected patients were enrolled between August2016 and February2017. Inclusion criteria: ≥18 years with undetectable HIV viral load. Exclusion criteria: pregnancy; alcohol intake ≥20 g/day and co-infection B or C viruses. Patients underwent ultrasound (US) to diagnose liver steatosis. Significant fibrosis (≥F2) was estimated if at least one of the following were present: APRI > 1.0, FIB4 > 3 and/or liver stiffness ≥7.1kPa. Subjects with TE ≥ 7.1kPa were proposed a liver biopsy and NAFLD Scoring System (NAS) ≥ 3 was considered as diagnosis of NASH. A total of 98 patients were included. Liver steatosis was diagnosed in 31 patients (31.6%) and was independently associated with male gender, BMI, ALT and total bilirubin levels. The prevalence of significant fibrosis assessed by TE, APRI and FIB4 was 26.9%, 6.4% and 3.2%, respectively. Seven patients had a TE result ≥7.1kPa. NASH was found in 5 (83.3%). Among HIV infected patients undergoing ART, almost one third have NAFLD. Neither TE, APRI or FIB4 were able to act as surrogates for significant liver fibrosis. Nevertheless, TE ≥ 7.1kPa was able to accurately select a subgroup of patients at risk for NASH.

OBJECTIVES: The aim of this study was to understand how demographic and treatment-related factors impact responses to fostemsavir-based regimens. DESIGN: BRIGHTE is an ongoing phase 3 study evaluating twice-daily fostemsavir 600 mg and optimized background therapy (OBT) in heavily treatment-experienced individuals failing antiretroviral therapy with limited treatment options (Randomized Cohort 1-2 and Nonrandomized Cohort 0 fully active antiretroviral classes). METHODS: Virologic response rates (HIV-1 RNA

Objective: The study aimed to assess the role of TE in HIV-infected patients with NAFLD. Methods: HIV infected patients undergoing ART were enrolled between August2016 and February2017. Inclusion criteria: ≥18 years with undetectable HIV viral load. Exclusion criteria: pregnancy; alcohol intake ≥20g/day and co-infection with hepatitis B or C. Patients underwent abdominal US to diagnose liver steatosis. Significant fibrosis (≥F2) was considered when APRI>1.0, FIB4>3 and liver stiffness ≥7.1kPa. Subjects with TE ≥7.1kPa were proposed a liver biopsy and the NAFLD Scoring System ≥3 was considered as diagnosis of NASH. Poisson regression model was used to identify factors associated with liver steatosis. Results: 98 patients were included. The mean age of the subjects was 49±11 years and 53 (54.1%) were males. Liver steatosis was diagnosed in 31 patients (31.6%) and was independently associated with male sex (PR= 2.18) and higher BMI (PR=1.08). Among the 31 patients with NAFLD, 26 showed results for TE, APRI and FIB4. The prevalence of significant fibrosis assessed by TE, APRI and FIB4 was 26.9%, 6.4% and 3.2%, respectively. Seven patients (26.9%) had a TE result ≥7.1kPa, which was associated with higher triglyceride levels, FIB4 score and CAP values. Liver biopsy was perfomed on six of those with TE ≥7.1kPa and NASH was found in 5 (83.3%) and liver fibrosis without NASH in one. Conclusions: NAFLD prevalence in HIV infected patients is higher than general population. TE ≥7.1kPa was not able to diagnose significant fibrosis, but accurately detect a subgroup of patients with high risk for NASH among HIV monoinfected individuals with steatosis.

Although a potential involvement of the CCR5Δ32 variant has already been suggested in relation to susceptibility to hepatitis C virus (HCV) infection, data from the literature is still quite controversial. Thus, our study evaluated the influence of the CCR5Δ32 allele variant in HCV infection, HCV/HIV co-infection, and HCV-related diseases in individuals from southern Brazil. A total of 1352 individuals were included in this study, divided into the following groups: Control (n = 274); HCV+ (n = 674); HIV+ (n = 300); HCV+/HIV+ (n = 104). Individuals from the HCV+ group were further stratified according to clinical/histological criteria, as HCV+/control (n = 124); HCV+/fibrosis (n = 268); HCV+/cirrhosis (n = 190); HCV+/hepatocarcinoma (n = 92). Considering all individuals included in this study, the following genotype frequencies were observed: wild-type homozygous (wt/wt), 88.76%; heterozygous (wt/Δ32), 10.72%; variant homozygous (Δ32/Δ32), 0.52%. Genotypic frequencies were very similar between the groups. Of note, the frequency of the Δ32 homozygous was quite similar comparing control uninfected against the HCV+ individuals (p > 0.999). The overall Δ32 allele frequency was estimated at 5.88%. Considering the number of Δ32 allele carriers and non-carriers, no statistically significant differences (p > 0.05) between the groups were observed, suggesting that the CCR5Δ32 variant does not influence the susceptibility to HCV infection, HCV/HIV co-infection, or HCV-related diseases in individuals from southern Brazil.

The aim of this study was to determine the effect of supervised exercise and folinic acid supplementation on endothelial function in HIV-infected individuals. A randomized clinical trial, double blinded, was conducted with 16 HIV-infected individuals, antiretroviral therapy (at least 6 months) with undetectable viral load (50 copies/mL), and CD4 count 200 cells/mm

The genetic background of human populations can influence the susceptibility and outcome of infection diseases. Toll-like receptors (TLRs) have been previously associated with susceptibility to human immunodeficiency virus (HIV) infection, disease progression and hepatitis C, virus (HCV) co-infection in different populations, although mostly in Europeans. In this study, we investigated the genetic role of endosomal TLRs on susceptibility to HIV infection and HCV co-infection through the analysis of TLR7 rs179008, TLR8 rs3764880, TLR9 rs5743836 and TLR9 rs352140 polymorphisms in 789 Brazilian individuals (374 HIV+ and 415 HIV−), taking into account their ethnic background. Amongst the 357 HIV+ individuals with available data concerning HCV infection, 98 were positive. In European descendants, the TLR9 rs5743836 C carriers displayed a higher susceptibility to HIV infection [dominant, Odds Ratio (OR) = 1.53; 95% CI: 1.05–2.23; P = 0.027]. In African descendants, TLR9 rs5743836 CT genotype was associated with protection to HIV infection (codominant, OR = 0.51; 95% CI: 0.30–0.87; P = 0.013). Also, the TLR9 rs352140 AA variant genotype was associated with susceptibility to HIV+/HCV+ co-infection in African descendants (recessive, OR = 2.92; 95% CI: 1.22–6.98, P = 0.016). These results are discussed in the context of the different ethnic background of the studied individuals highlighting the influence of this genetic/ethnic background on the susceptibility to HIV infection and HIV/HCV co-infection in Brazilian individuals.

Objectives: HIV-1 heterosexual transmission among individuals on antiretroviral treatment (ART) with undetectable viremia is extremely rare. The aim of this study was to evaluate the risk of sexual HIV-1 transmission and other sexually transmitted infections (STIs) in HIV-1 serodifferent couples while the index partner is on ART. Methods: HIV transmission was evaluated in 200 HIV-1 heterosexual serodifferent couples in a stable relationship (≥3 months). All HIV-positive individuals had been on ART for ≥3 months and had been followed up for a median preceding time of 4.5 years (range 0.3–16 years) at the HIV couples clinic at Hospital Nossa Senhora da Conceição in Porto Alegre, Brazil. Following written informed consent, participants responded to demographic/behavioral questionnaires. Quantitative PCR for HIV RNA, T-cell subsets, and STI testing (syphilis, herpes, human papillomavirus, gonorrhea, and bacterial vaginosis) were performed. Self-collected vaginal swabs were obtained for quantitative HIV genital viral load testing. Results: Among 200 couples, 70% of index partners were female. Five seroconversions were observed; the HIV infection incidence was 2.5% (95% confidence interval 0.8% to 5.7%). Mean plasma viral load results were higher in HIV transmitters compared to non-transmitters (p = 0.02). The presence of STIs was significantly greater in couples who seroconverted (60.0% vs. 13.3%; odds ratio 9.75, 95% confidence interval 1.55–61.2; p = 0.023). The duration of undetectable HIV viremia and presence of STIs were associated with HIV transmission. Conclusions: Undetectable viremia was the main factor associated with non-transmissibility of HIV in this setting. Keywords: HIV-1 transmission, Couples, STIs, ART for prevention

Background: Development of drug-resistance mutations is the main cause of failure in antiretroviral therapy. In Brazil, there is scarce information on resistance pattern for patients failing antiretroviral therapy. Objectives: To define the HIV mutational profile associated with drug resistance in Brazilian patients from 5 large cities, after first, second or further failures to antiretroviral therapy. Methods: We reviewed genotyping results of 1520 patients failing therapy in five Brazilian cities. Frequency of mutations, mean number of active drugs, viral susceptibility to each antiretrovirals drug, and regional differences were assessed. Results: Mean time of antiretrovirals use was 22.7 ± 41.1 months. Mean pre-genotyping viral load was 4.2 ± 0.8 log (2.1 ± 2.0 after switching antiretrovirals). Mean number of remaining active drugs was 9.4, 9.0, and 7.9 after 1st, 2nd, and 3rd failure, respectively. We detected regional variations in drug susceptibility: while BA and RS showed the highest (∼40%) resistance level to ATV/r, FPV/r and LPV/r, in the remaining cities it was around half of this rate. We detected 90% efavirenz/nevirapine resistance in SP, only 45% in RS, and levels between 25% and 30% in the other cities. Regarding NRTI, we found a similar pattern, with RJ presenting the highest, and CE the lowest susceptibility rates for all NRTI. Zidovudine resistance was detected in only 3% of patients in RJ, against 45–65% in the other cities. RJ and RS showed 3% resistance to tenofovir, while in CE it reached 55%. DRV/r (89–97%) and etravirine (61–85%) were the most active drugs, but again, with a wide variation across cities. Conclusions: The resistance mutational profile of Brazilian patients failing antiretroviral therapy is quite variable, depending on the city where patients were tested. This variation likely reflects distinctive choice of antiretrovirals drugs to initiate therapy, adherence to specific drugs, or circulating HIV-1 strains. Overall, etravirine and DRV/r remain as the most active drugs. Keywords: HIV, Resistance, Brazil, Mutations

BACKGROUND HIV-1 gp120 binds to integrin α4β7, a homing receptor of lymphocytes to gut-associated lymphoid tissues. This interaction is mediated by the LDI/V tripeptide encoded in the V2-loop. This tripeptide mimics similar motifs in mucosal addressin cellular adhesion molecule (MAdCAM) and vascular CAM (VCAM), the natural ligands of α4β7. In this study, we explored the association of V2-loop LDI/V mimotopes with transmission routes and patterns of disease progression in HIV-infected adult and pediatric patients. HIV-1 env sequences available in the Los Alamos HIV Sequence database were included in the analyses. METHODS HIV-1 V2-loop sequences generated from infected adults and infants from South and Southeast Brazil, and also retrieved from the Los Alamos database, were assessed for α4β7 binding tripeptide composition. Chi-Square/Fisher Exact test and Mann Whitney U test were used for tripeptide comparisons. Shannon entropy was assessed for conservancy of the α4β7 tripeptide mimotope. RESULTS We observed no association between the tripeptide composition or conservation and virus transmission route or disease progression. However, LDI was linked to successful epidemic dissemination of HIV-1 subtype C in South America, and further to other expanding non-B subtypes in Europe and Asia. In Africa, subtypes showing increased LDV prevalence evidenced an ongoing process of selection toward LDI expansion, an observation also extended to subtype B in the Americas and Western Europe. CONCLUSIONS The V2-loop LDI mimotope was conserved in HIV-1C from South America and other expanding subtypes across the globe, which suggests that LDI may promote successful dissemination of HIV at local geographic levels by means of increased transmission fitness.

Background An undetectable serum HIV-1 load is key to effectiveness of antiretroviral (ARV) therapy, which depends on adherence to treatment. We evaluated factors possibly associated with ARV adherence and virologic response in HIV-infected heterosexual individuals. Methods A cross-sectional study was conducted in 200 HIV-1 serodiscordant couples and 100 unpartnered individuals receiving ARV treatment at a tertiary hospital in southern Brazil. All subjects provided written informed consent, answered demographic/behavioral questionnaires through audio computer-assisted self-interviews (ACASI), and collected blood and vaginal samples for biological markers and assessment of sexually transmitted infections (STIs). HIV-negative partners were counseled and tested for HIV-1. Results The study population mean age was 39.9 years, 53.6% were female, 62.5% were Caucasian, 52.6% had incomplete or complete elementary education, 63.1% resided in Porto Alegre. Demographic, behavioral and biological marker characteristics were similar between couples and single individuals. There was an association between adherence reported on ACASI and an undetectable serum viral load (P

OBJECTIVE: The aim of this study was to discover the prevalence of overweight, obesity and cardiovascular risk in our HIV/AIDS outpatients according to sex, antiretroviral therapy and other variables. SUBJECTS AND METHODS: Patients underwent an anthropometric assessment. Body mass index and waist circumference were used to classify their nutritional status and their cardiovascular risk. RESULTS: The majority of the 345 patients (58.8%) were males. Obesity was detected in 8.3% of them; 34.2% were overweight, and 5.2% malnourished. Near half of them (51.3%) had some cardiovascular risk, with increased risk in 24.6% of them, and substantially increased risk in 26.7% of them. CONCLUSIONS: Overweight and obesity were highly prevalent. Women were more frequently obese (OR = 3.53; IC 95%, 1.47 < OR < 8.69), and their cardiovascular risk was often higher (OR = 6.97; IC 95%, 4.16 < OR < 11.76). The prevalence of obesity and cardiovascular risk did not change according to antiretroviral therapy or other variables. OBJETIVO: Conhecer a prevalência de sobrepeso, obesidade e risco cardiovascular em nossos pacientes ambulatoriais com HIV/AIDS de acordo com o sexo, tratamento antirretroviral e outras variáveis. SUJEITOS E MÉTODOS: Os pacientes foram submetidos à avaliação antropométrica. O índice de massa corporal e a medida da circunferência da cintura foram utilizados para classificar o estado nutricional e o risco cardiovascular. RESULTADOS: A maior parte dos 345 pacientes (58,8%) era do sexo masculino. A obesidade foi detectada em 8,3% deles; 34,2% tinham sobrepeso e 5,2%, desnutrição. Quase a metade (51,3%) apresentou algum risco cardiovascular, com risco elevado em 24,6% e muito elevado em 26,7%. CONCLUSÕES: O sobrepeso e a obesidade têm elevada prevalência. As mulheres são mais frequentemente obesas (OR = 3,53; IC 95%, 1,47 < OR < 8,69) e seu risco cardiovascular é frequentemente mais alto (OR = 6,97; IC 95%, 4,16 < OR < 11,76). A prevalência de obesidade e de risco cardiovascular não se alterou conforme o tratamento antirretroviral ou outras variáveis.

Efavirenz is among the most widely used antiretroviral drugs. Increased efavirenz exposure has been associated with CNS side effects and also with the chance of emergence of resistance upon treatment interruptions. The objective of this study was to evaluate factors associated with efavirenz plasma concentrations in a cohort of HIV-infected individuals.From July 2009 to March 2010, HIV-infected patients with efavirenz as part of antiretroviral therapy (600 mg at night), undetectable viral load for at least 1 year and CD4 cell count200 cells/mm(3) were consecutively enrolled at the HIV/AIDS ambulatory care unit in southern Brazil. Plasma samples were taken 18-23 h after efavirenz last dose and analysed by validated ultra-performance liquid chromatography.Forty-one subjects were included (21 females). Mean age and weight were 45.4 years and 70.9 kg, respectively. Mean efavirenz plasma concentration was 2.20 ± 2.17 mg/L. Most plasma concentrations (73%) were within the therapeutic window (1-4 mg/L); 17% were below and 10% above the limits. There were no significant associations between efavirenz concentration and age, CD4 cell count, time on antiretroviral treatment and gender. There was significant and inverse correlation between efavirenz concentrations and body weight (P = 0.013) and body mass index (P = 0.001).In this cohort of well-controlled HIV-positive individuals, patients with lower weight or body mass index had a higher chance of presenting elevated plasma concentrations of efavirenz. Therapeutic drug monitoring to adjust dose might be a helpful tool to decrease efavirenz dose in order to minimize costs and adverse effects.

Individuals with syphilis have higher chance of having HIV, and syphilis' genital ulcers increases HIV transmission rate. Nevertheless, there are few well-documented studies about HIV and syphilis co-infection and its risk factors. The study was based on 2262 HIV infected individuals from South Brazilian HIV cohort, which began in 1991, and this analysis included individuals who were included in the cohort until November 2008. Inclusion criteria were having CD4 + T cell count and viral load at baseline, and syphilis serology tests (venereal disease research laboratory [VDRL]1:64 or a positive VDRL plus a positive treponemal test). A total of 1012 patients were included; 580 were men (57%); mean age at HIV diagnosis was 33 years; 591 (58%) had previous diagnosis of AIDS; most of the individuals acquired HIV from sexual contact (47.9% heterosexual and 31.7% men who had sex with men [MSM]); and 759 (75%) were on antiretroviral therapy. The prevalence of syphilis was 20.5% (208). After multivariate analysis, being male (2.01; 95% CI, 1.23-3.27; p = 0.005) and MSM (1.91; 95% CI, 1.25-2.90; p = 0.002) were significantly associated to HIV and syphilis co-infection. Males and MSM were associated with higher risk of this co-infection. Our findings may reflect that this particular population is still engaging in unprotected sexual intercourse, and efforts should be made to better target this specific group as they might perpetuate these infections.

Metabolic complications continue to play a major role in the management of HIV infection. Dyslipidemia associated with HIV infection and with the use of combined antiretroviral therapy includes elevations in triglycerides, reduced high-density cholesterol, and variable increases in low-density and total cholesterol. The association between dyslipidemia and specific antiretroviral agents has been underscored. Multiple pathogenic mechanisms by which HIV and antiretroviral agents lead to dyslipidemia have been hypothesized, but they are still controversial. The potential clinical and pathological consequences of HIV-associated hyperlipidemia are not completely known, but several studies reported an increased risk of coronary artery disease in HIV-positive individuals receiving combined antiretroviral therapy. HIV-infected persons who have hyperlipidemia should be managed similarly to those without HIV infection in accordance with the National Cholesterol Education Program. Life style changes are the primary target. Statins and fibrates and/or modification in antiretroviral therapy are possible approaches to this problem. Keywords: HIV/AIDS, dyslipidemia, combined antiretroviral therapy, nutrition, Public Health

Human immunodeficiency virus (HIV)-infected subjects have increased levels of oxidative stress which could impair immunological function and therefore contribute to the progression of AIDS. These characteristics are usually evaluated at rest and responses to exercise have yet to be evaluated. The aim of the present study was to assess the effect of a bout of aerobic exercise followed by resistance exercises on antioxidant system in HIV-infected and non-HIV subjects. There were included 14 cases (HIV-positive) and 14 controls (HIV-negative). The exercise protocol consisted of a single session of 20 minutes on a cycloergometer followed by a set of six resistance exercises. The activity of glutathione S-transferase (GST) and catalase were measured in plasma samples, total glutathione (TGSH) and thiobarbituric acid reactive substances (TBARS) were measured in erythrocytes. T CD4+ cells, T CD8+, viral load, complete blood count, and white blood count were also assessed. All measurements were performed at three times: baseline, after aerobic exercise, and after resistance exercises. At baseline, the HIV group had lower GST activity than controls, but after the exercise session GST values were similar in both groups. Compared to the control group TGSH was significantly lower in the HIV group at baseline, after aerobic and resistance exercises. The control group presented higher TBARS values after aerobic exercise compared to the HIV group. The neutrophil count was lower in the HIV group after aerobic and resistance exercises. These data indicate that HIV-infected subjects had lower antioxidant activity at rest. Physical exercise stimulated the enzymatic activity similarly in both groups.

International audience; BACKGROUND: Few data are available on the long-term immunologic response to antiretroviral therapy (ART) in resource-limited settings, where ART is being rapidly scaled up using a public health approach, with a limited repertoire of drugs. OBJECTIVES: To describe immunologic response to ART among ART patients in a network of cohorts from sub-Saharan Africa, Latin America, and Asia. STUDY POPULATION/METHODS: Treatment-naive patients aged 15 and older from 27 treatment programs were eligible. Multilevel, linear mixed models were used to assess associations between predictor variables and CD4 cell count trajectories following ART initiation. RESULTS: Of 29 175 patients initiating ART, 8933 (31%) were excluded due to insufficient follow-up time and early lost to follow-up or death. The remaining 19 967 patients contributed 39 200 person-years on ART and 71 067 CD4 cell count measurements. The median baseline CD4 cell count was 114 cells/microl, with 35% having less than 100 cells/microl. Substantial intersite variation in baseline CD4 cell count was observed (range 61-181 cells/microl). Women had higher median baseline CD4 cell counts than men (121 vs. 104 cells/microl). The median CD4 cell count increased from 114 cells/microl at ART initiation to 230 [interquartile range (IQR) 144-338] at 6 months, 263 (IQR 175-376) at 1 year, 336 (IQR 224-472) at 2 years, 372 (IQR 242-537) at 3 years, 377 (IQR 221-561) at 4 years, and 395 (IQR 240-592) at 5 years. In multivariable models, baseline CD4 cell count was the most important determinant of subsequent CD4 cell count trajectories. CONCLUSION: These data demonstrate robust and sustained CD4 response to ART among patients remaining on therapy. Public health and programmatic interventions leading to earlier HIV diagnosis and initiation of ART could substantially improve patient outcomes in resource-limited settings.

To compare the gender distribution of HIV-infected adults receiving highly active antiretroviral treatment (HAART) in resource-constrained settings with estimates of the gender distribution of HIV infection; to describe the clinical characteristics of women and men receiving HAART.The Antiretroviral Therapy in Lower-Income Countries, ART-LINC Collaboration is a network of clinics providing HAART in Africa, Latin America, and Asia. We compared UNAIDS data on the gender distribution of HIV infection with the proportions of women and men receiving HAART in the ART-LINC Collaboration.Twenty-nine centers in 13 countries participated. Among 33,164 individuals, 19,989 (60.3%) were women. Proportions of women receiving HAART in ART-LINC centers were similar to, or higher than, UNAIDS estimates of the proportions of HIV-infected women in all but two centers. There were fewer women receiving HAART than expected from UNAIDS data in one center in Uganda and one center in India. Taking into account heterogeneity across cohorts, women were younger than men, less likely to have advanced HIV infection, and more likely to be anemic at HAART initiation.Women in resource-constrained settings are not necessarily disadvantaged in their access to HAART. More attention needs to be paid to ensuring that HIV-infected men are seeking care and starting HAART.

Objective: This study aimed to investigate the role of Human Leukocyte Antigen (HLA)-G in the susceptibility to HIV-1 infection through the analysis of the HLA-G 30 untranslated region (UTR) polymorphisms 14 bp insertion/deletion (rs66554220) and +3142C>G (rs1063320). Design: We analyzed 582 HIV-1 infected patients and 626 uninfected individuals from Brazil and Italy in a case-control study. Methods: HLA-G polymorphisms were genotyped using PCR, PCR-RFLP assays or direct sequencing. All analyses were stratified by ethnicity. Genotypic, allelic and diplotypic frequencies were compared between HIV-1 infected subjects and controls using Chi-square or Fischer exact tests. Also, haplotypic frequencies were estimated using MLocus software. Results: African-derived HIV-infected individuals presented a higher frequency of the 14 bp insertion allele as compared to non-infected individuals (0.468 versus 0.373, respectively; pBonf = 0.010). A higher frequency of the 14 bp insertion +3142G (insG) haplotype (0.456 versus 0.346, p < 0.001) and the insG/ insG diplotype (OR = 1.88, 95%CI = 1.08–3.23, p = 0.021) was observed among African-derived patients as compared to uninfected controls. Also, we observed a higher frequency of the ins/ins genotype among African-derived HIV patients co-infected with HCV (OR = 2.78, 95%CI = 1.20–6.49, p = 0.008). Conclusions: Our data point out to an increased frequency of alleles and genotypes associated with low HLA-G expression among African-derived patients, suggesting a potential role for HLA-G in the susceptibility to HIV-1 infection and HCV co-infection in those individuals.

This study evaluated the impact of seven single nucleotide polymorphisms in five candidate genes (ABCB1, ABCC2, ABCC4, SLC22A6, and SLC22A11) in relation to nephrotoxicity associated with highly active antiretroviral therapy (HAART) in HIV-infected individuals.The following single nucleotide polymorphisms were genotyped by real-time PCR: ABCB1 rs1045642, ABCC2 rs717620 and rs2273697, ABCC4 rs1751034 and rs3742106, SLC22A6 rs11568626, and SLC22A11 rs11231809 in 507 HIV-infected patients from the city of Porto Alegre, Southern Brazil, receiving HAART for, at least, 1 year.From the 507 HIV-infected patients recruited, 19.1% presented a reduction in estimated glomerular filtration rate (eGFR). A total of 16 (3.2%) patients fulfilled the criteria for chronic kidney disease (defined as eGFR60 ml/min/1.73 m). Individuals carrying at least one T allele of ABCC2 -24 CT (rs717620) presented lower eGFR than C/C homozygotes (104 ± 22 vs. 108 ± 22 ml/min/1.73 m, independent-samples t-test, P=0.040). In multivariate analysis, the predictors associated with decreased eGFR were time of treatment, tenofovir use, atazanavir/ritonavir use, and carrying one T allele of ABCC2 -24 CT.Our data support the importance of genetic factors in the etiology of nephrotoxicity in patients treated with HAART. Studies to verify treatment implications of genotyping before HAART initiation may be advisable to guide the selection of an appropriate antiretroviral therapy regimen.

HIV related mutations can be associated with decreased susceptibility to antiretrovirals and treatment failures. There is scarce information about HIV mutations in persons failing HIV treatment in North of Brazil. Our aim was to evaluate evolution of HIV subtypes and mutations patterns related to antiretroviral therapy in this region. We investigated HIV resistance profile in adults failing antiretroviral regimen in Northern Brazil from January, 2004, through December, 2013. Genotype data was evaluated through Stanford University algorithm. There were 377 genotypes from different individuals to evaluate. Resistance mutations were similar to worldwide reports and related to antiretroviral exposure. Most prevalent mutations in the reverse transcriptase gene were M184V (80.1%) and K130N (40.6%). Thymidine associated mutations were more frequent in multiexperienced patients. Most common protease mutations were M46I, V82A, I54V, L90M, I84V, M46L, and L76V. Subtype B was the most prevalent (90.7%). There were differences between subtypes B and non-B mutations. We documented for the first time subtypes and patterns of HIV associated mutations in Northern Brazil. A1 subtype was identified for the first time in this area. Depending on drug regimen and how experienced the patient is, an empirical switch of a failing antiretroviral treatment could be a reasonable option.

Adverse effects are important determinants of quality of life (QOL) during highly active antiretroviral therapy (HAART). The PLATO study investigated the association between changes in patient-reported outcomes including QOL and substitution with lopinavir/ritonavir in patients experiencing side effects (SEs).HIV-1-infected participants (N = 849) with undetectable viral load experiencing Grade-2 SEs of the protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) component of their HAART regimen were randomized to immediate (baseline) or deferred (week 4) substitution with lopinavir/ritonavir soft-gel capsules 400/100 mg bid. The primary endpoint was change in the total score from the AIDS Clinical Trials Group (ACTG) Symptoms Distress Module (ASDM), supplemented with two items for nephrolithiasis. Secondary endpoints included Medical Outcomes Study (MOS)-HIV scores and Center for Epidemiologic Studies-Depression (CES-D) scores.Immediate substitution resulted in improved ASDM total score at week 4 compared with deferred substitution (p.001) and significant improvements in all MOS-HIV domains, while significant improvement was observed in CES-D scores at week 8. Primary SEs resolved at week 8 in 65% of participants in the immediate substitution group. Suppression of HIV-1 was maintained. Treatment was well-tolerated and associated with elevations in cholesterol and triglycerides.Substitution with LPV/r improved patient-reported outcomes including QOL in patients experiencing Grade-2 SEs, while maintaining viral suppression.

Purpose: Highly active antiretroviral therapy has improved the prognosis of human immuno deficiency virus type 1 (HIV-1)-infected individuals, but it has been associated with the development of metabolic and fat distribution abnormalities known as the lipodystrophy syndrome. This study tested the hypothesis that aerobic exercise training added to a low-lipid diet may have favorable effects in HIV-1-infected individuals with dyslipidemia and lipodystrophy. Methods: Thirty healthy subjects, carriers of HIV-1, with dyslipidemia and lipodystrophy, all of whom were using protease inhibitors and/or non-nucleoside reverse transcriptase inhibitors, were randomly assigned to participate in either a 12-wk program of aerobic exercise or a 12-wk stretching and relaxation program. All subjects received recommendations for a low-lipid diet. Before and after intervention, peak oxygen uptake, body composition, CD4, viral load, lipid profile, and plasma endothelin-1 levels were measured. Results: Peak oxygen uptake increased significantly in the diet and exercise group (mean +/- SD: 32 +/- 5 mL[middle dot]kg-1[middle dot]min-1 before; 40 +/- 8 mL[middle dot]kg-1[middle dot]min-1 after) but not in the diet only group (34 +/- 7 mL[middle dot]kg-1[middle dot]min-1 before; 35 +/- 8 mL[middle dot]kg-1[middle dot]min-1 after). Body weight, body fat, and waist-to-hip ratio decreased significantly and similarly in the two groups. There were no significant changes in immunologic variables in either group. Likewise, plasma triglycerides, total cholesterol, and HDL cholesterol levels did not change significantly in either group. Plasma endothelin-1 levels were elevated in both groups and presented no significant changes during the study. Conclusion: HIV-seropositive individuals with lipodystrophy and dyslipidemia submitted to a short-term intervention of low-lipid diet and aerobic exercise training are able to increase their functional capacity without any consistent changes in plasma lipid levels.

OBJECTIVE To assess predictors of virologic response 6 months after initiation of highly active antiretroviral therapy (HAART) in a cohort of HIV-infected patients in Brazil. METHODS Treatment-naive patients who started HAART between 1996 and 2004 and had information on viral load at 3-9 months were included. Information was collected on demographic characteristics, antiretroviral regimen, adherence, AIDS diagnosis, baseline CD4 cell count, and viral load. Virologic failure (VF) was defined as viral load > or =400 copies/mL at 6 months or death before completion of 6 months of therapy. RESULTS Among 454 patients who met the inclusion criteria, VF occurred in 127 (28.0%). In univariate analysis, VF was associated with younger age (median 34 vs. 37 years, P = 0.003), AIDS diagnosis (relative risk [RR] 1.18, P = 0.009), higher baseline viral load (5.34 vs. 5.00, P = 0.0002), lower baseline CD4 cell count (86 vs. 182, P = 0.006), nonadherence (RR 1.39, P < 0.0001), regimen containing 1 single protease inhibitor, as compared with ritonavir-boosted regimens (odds ratio [OR] 8.5, P < 0.0001), and year therapy initiated before 1999 (P < 0.0001). To minimize the systematic effect of therapy indication, we analyzed the subset of 158 patients with CD4 count < or =200 cells/microL who started therapy after 1999. After adjusting for age, education, adherence, regimen, and baseline viral load, nonadherence (OR 8.78, P = 0.02), and fewer years of education (OR 6.05, P = 0.05) remained associated with VF. CONCLUSIONS A significant improvement was found in virologic suppression over time, consistent with the introduction of nonnucleoside reverse transcriptase inhibitors and ritonavir-boosted regimens into clinical practice. With currently available therapies, compliance and education were shown to be predictors of virologic response, particularly in more immunocompromised patients.

The α4β7 is a lymphocyte homing receptor to the gut-associated lymphoid tissue (GALT). HIV-1 gp120 binds to α4β7 integrin through a mimetic tripeptide in V2 and ensures successful infection of GALT. In the present report, we investigated the presence of polymorphisms in the α4β7 cytoplasmic and α4 N-terminal binding domains and their potential association with susceptibility to HIV infection or disease progression. Subjects displaying distinct categories of disease progression or transmission routes (HIV-positive adults, vertically infected infants, and seronegative subjects) had their ITGA4 and ITGB7 gene segments corresponding to virus binding sites and C-terminal domains PCR amplified and sequenced. An absolute conservation of the studied regions was observed in all patients and controls. Albeit polymorphisms in α4β7 may exist in other regions not tracked in this study, α4β7 activation and binding domains do not seem to be polymorphic and are not correlated with distinct patterns of HIV transmission or disease progression.

Objective: To evaluate the factors associated with plasma concentrations of atazanavir (ATV) in a cohort of well-controlled HIV infected subjects (undetectable viremia). Design: Cross-sectional study where 69 subjects were consecutively enrolled between April and November, 2011. Methods: Patients had to be on atazanavir for at least six months, undetectable viral load for a period equal to or longer than 12 months, T CD4+ lymphocyte count higher than 200 cells/mm3, and aged between 18 years and 70 years old. Exclusion criteria were pregnancy, any neurologic disease, active opportunistic disease, hepatitis or cancer. Atazanavir plasma levels were measured by ultra-performance liquid chromatography. Results and discussion: Overall, 54 patients (mean age of 47 years and 50% women) were included in the analysis. Those without ritonavir (unboosted atazanavir) had statistically lower plasma concentrations than those with ritonavir boosted atazanavir (p = 0.001) and total and indirect bilirubin were statistically associated with plasma concentration of atazanavir (r = 0.32 and r = 0.33 respectively; p

This study evaluated the impact of 9 single nucleotide polymorphisms (SNPs) in 6 candidate genes (APOB, APOA5, APOE, APOC3, SCAP, andLDLR) over dyslipidemia in HIV-infected patients on stable antiretroviral therapy (ART) with undetectable viral loads. Blood samples were collected from 614 patients at reference services in the cities of Porto Alegre, Pelotas, and Rio Grande in Brazil. The SNPs were genotyped by conventional polymerase chain reaction (PCR) and real-time PCR. The prevalence of dyslipidemia was particularly high among the protease inhibitors-treated patients (79%).APOE(rs429358 and rs7412) genotypes andAPOA5−1131T>C (rs662799) were associated with plasma triglycerides (TG) and low-density-lipoprotein cholesterol levels (LDL-C). TheAPOA5−1131T>C (rs662799) andSCAP2386A>G (rs12487736) polymorphisms were significantly associated with high-density-lipoprotein cholesterol levels. The mean values of the total cholesterol and LDL-C levels were associated with both theAPOBSPIns/Del(rs17240441) andAPOB XbaI(rs693) polymorphisms. In conclusion, our data support the importance of genetic factors in the determination of lipid levels in HIV-infected individuals. Due to the relatively high number of carriers of these risk variants, studies to verify treatment implications of genotyping before HAART initiation may be advisable to guide the selection of an appropriate antiretroviral therapy regimen.

HIV-infected individuals present a cluster of conditions that activate or injure the vascular endothelium. The administration of folates may exert beneficial effects on endothelial function in different populations at risk for cardiovascular disease. The aim of this study was to determine the effects of 4 wk of folinic acid supplementation on forearm vascular responses during reactive hyperemia in HIV-infected patients under highly active antiretroviral therapy.This was a prospective, randomized, double-blind, placebo-controlled trial to compare the effects of 4 wk of daily ingestion of 5 mg of folinic acid (n = 15) or placebo (n = 15). Participants had to have been on antiretroviral therapy (ART) for at least 6 mo before enrollment, with undetectable viral load, and CD4 cell count200 cells/mm(3). Vascular function was evaluated with venous occlusion plethysmography at baseline and after 4 wk, for the determination of brachial artery reactive hyperemia, and after isosorbide dinitrate administration.The groups were comparable. The mean age of patients was 45 y; there were eight women in each group. There was no difference regarding ART regimen. The supplementation of folinic acid produced a significant improvement in reactive hyperemia (from 14.9 to 21.2 mL•min•100 mL). The same was not observed in placebo group (from 15.3 to 14.6 mL•min•100 mL; group P, 0.017; time P0.001; interaction P0.001). Endothelium-independent responses remained unchanged.Short-term folinic acid supplementation improved vascular reactivity in HIV-infected individuals enrolled in the studied. As folate supplementation is safe and relatively inexpensive, long-term clinical trials should be conducted.

Background Changes in CD4 cell counts are poorly documented in individuals with low or moderate-level viremia while on antiretroviral treatment (ART) in resource-limited settings. We assessed the impact of on-going HIV-RNA replication on CD4 cell count slopes in patients treated with a first-line combination ART. Method Naïve patients on a first-line ART regimen with at least two measures of HIV-RNA available after ART initiation were included in the study. The relationships between mean CD4 cell count change and HIV-RNA at 6 and 12 months after ART initiation (M6 and M12) were assessed by linear mixed models adjusted for gender, age, clinical stage and year of starting ART. Results 3,338 patients were included (14 cohorts, 64% female) and the group had the following characteristics: a median follow-up time of 1.6 years, a median age of 34 years, and a median CD4 cell count at ART initiation of 107 cells/μL. All patients with suppressed HIV-RNA at M12 had a continuous increase in CD4 cell count up to 18 months after treatment initiation. By contrast, any degree of HIV-RNA replication both at M6 and M12 was associated with a flat or a decreasing CD4 cell count slope. Multivariable analysis using HIV-RNA thresholds of 10,000 and 5,000 copies confirmed the significant effect of HIV-RNA on CD4 cell counts both at M6 and M12. Conclusion In routinely monitored patients on an NNRTI-based first-line ART, on-going low-level HIV-RNA replication was associated with a poor immune outcome in patients who had detectable levels of the virus after one year of ART.

Objective: To investigate genetic single nucleotide polymorphisms (SNPs) in estrogen receptor-a (ERa) (ESR1, rs2234693, rs1801132, rs7757956 and rs2813544) and ERb (ESR2, rs3020450, rs7154455 and rs4986938) genes and relate them to the adverse effects lipodystrophy, dyslipidemia and metabolic syndrome as well as to differences in their prevalence between sexes in HIV-infected individuals on HAART. Design: Cross-sectional study. Methods: Blood samples and anthropometric measurements were collected from 614 patients at reference services in the cities of Porto Alegre, Pelotas and Rio Grande in Brazil. The SNPs were genotyped by real-time PCR. Results: The lipodystrophy subtype frequencies in patients of different sexes showed statistically significant differences; the atrophic pattern was more prevalent in men, and the hypertrophic pattern was more prevalent in women. Furthermore, metabolic syndrome prevalence was higher in women than in men. The ESR1 rs2813544 G-allele was associated with higher measurements of several anthropometric variables in women: BMI, total subcutaneous fat and subcutaneous fat of limbs. Additionally, patients who were AA homozygous for ESR2 rs3020450 presented an increased risk for developing lipoatrophy (prevalence ratio 1.37, 95% confidence interval 1.09–1.73, P ¼ 0.007). Conclusion: Significant differences in lipodystrophy and metabolic syndrome prevalence were detected between sexes. Moreover, the ESR1 gene (rs2813544) presented significant sex-specific associations with anthropometric variables, and the ESR2 gene (rs3020450) was associated with an increased risk of developing lipoatrophy. Our results suggest that these genes are in part responsible for the sexual dimorphism in fat tissue redistribution and patterns of lipodystrophy.

BACKGROUND: To determine the prevalence and associated factors with chronic kidney disease (CKD) in a cohort of HIV-positive individuals with undetectable viral load on HAART. METHODS: From March, 2009 to September 2009, 213 individuals between 18-70 years, period on HAART ≥12 months, viral load < 50 copies/mm(3), and CD4 ≥ 200 cells/mm(3), were consecutively enrolled at the outpatient clinic of Hospital de Clínicas, Porto Alegre, Brazil. Exclusion criteria were obesity, malnourishment, amputee, paraplegic, previous history of renal disease, pregnancy and hepatic insufficiency. Renal function was determined by estimated glomerular filtration rate (eGFR) assessed by the modification of diet in renal disease. CKD was defined as an eGFR less or equal than 60 ml/min/1.73 m(2), for a period of at least 3 months. Poisson regression was used to determine factors associated with CKD. RESULTS: CKD was diagnosed in 8.4% of the population, and after adjustment, the risk factors were hypertension (RR = 3.88, 95%CI, 1.84-8.16), time on HAART (RR = 1.15, 95%CI,1.03-1.27) and tenofovir exposure (RR = 2.25, 95%CI, 1.04-4.95). Higher weight (RR = 0.88 95%CI, 0.82-0.96) was associated to normal function. CONCLUSIONS: CKD was a common finding in this cohort of patients and was related to hypertension, time on HAART and tenofovir exposure. We suggest a more frequent monitoring of renal function, especially for those with risk factors to early identify renal impairment.

The purpose of this study was to evaluate the efficacy of dietary intervention on blood lipids of human immunodeficiency virus (HIV)-1-infected patients who are started on highly active antiretroviral therapy (HAART).Current guidelines recommend diet as first-step intervention for HIV-1-infected individuals with HAART-related dyslipidemia, but there is no evidence from randomized trials to support this recommendation.Eighty-three HIV-1-infected patients, naive from HAART, were randomly assigned to HAART with dietary intervention (diet group, n = 43) or HAART without dietary intervention (control group, n = 40) for 12 months. Diet, according to the National Cholesterol Education Program, was given every 3 months. Before and after intervention, 24-h food records and lipid profile were obtained. Data were analyzed by intention to treat, using mixed-effects models.Diet resulted in reduction of percentage of fat intake (from 31 ± 7% to 21 ± 3% of calories), while controls presented no change in percentage of fat intake. Plasma cholesterol (from 151 ± 29 mg/dl to 190 ± 33 mg/dl) and low-density lipoprotein cholesterol (from 85 ± 24 mg/dl to 106 ± 31 mg/dl) increased in the control group and were unchanged in the diet group. Plasma triglycerides were reduced by diet (from 135 ± 67 mg/dl to 101 ± 42 mg/dl) and increased in the control group (from 134 ± 70 mg/dl to 160 ± 76 mg/dl). After 1-year follow-up, 21% of patients who received diet had lipid profile compatible with dyslipidemia compared with 68% (p0.001) of controls.Among HIV-1-positive individuals naive of previous treatment, diet prevents dyslipidemia associated with HAART. (Effect of Nutritional Intervention on the Lipid Profile of HIV-Positive Patients Who Start HAART: a Randomized Trial; NCT00429845).

BACKGROUND: Tuberculosis (TB) is a common diagnosis in human immunodeficiency virus (HIV) infected patients on antiretroviral treatment (ART). OBJECTIVE: To describe TB-related practices in ART programmes in lower-income countries and identify risk factors for TB in the first year of ART. METHODS: Programme characteristics were assessed using standardised electronic questionnaire. Patient data from 2003 to 2008 were analysed and incidence rate ratios (IRRs) calculated using Poisson regression models. RESULTS: Fifteen ART programmes in 12 countries in Africa, South America and Asia were included. Chest X-ray, sputum microscopy and culture were available free of charge in respectively 13 (86.7%), 14 (93.3%) and eight (53.3%) programmes. Eight sites (53.3%) used directly observed treatment and five (33.3%) routinely administered isoniazid preventive treatment (IPT). A total of 19 413 patients aged ≥16 years contributed 13 227 person-years of follow-up; 1081 new TB events were diagnosed. Risk factors included CD4 cell count (>350 cells/μl vs.

OBJECTIVE This study investigates the role of mannose-binding lectin (MBL) in the susceptibility to HIV-1 infection analyzing polymorphisms located at the MBL2 promoter and exon 1 regions. MATERIALS AND METHODS The prevalence of MBL2 variant alleles was investigated in 410 HIV-1-infected patients from the South Brazilian HIV cohort and in 345 unexposed uninfected healthy individuals. The promoter variants were genotyped using polymerase chain reaction with sequence-specific primers (PCR-SSP) and exon 1 variants were analyzed by real-time PCR using a melting temperature assay and were confirmed by PCR-restriction fragment length polymorphism (RFLP). MBL2 genotypic and allelic frequencies were compared between HIV-1-infected patients and controls using the chi-squared tests. RESULTS The analyses were performed subdividing the individuals according to their ethnic origin. Among Euro-derived individuals a higher frequency of the LX/LX genotype was observed in patients when compared to controls (P < 0.001). The haplotypic analysis also showed a higher frequency of the haplotypes associated with lower MBL levels among HIV-1-infected patients (P = 0.0001). Among Afro-derived individuals the frequencies of LY/LY and HY/HY genotypes were higher in patients when compared to controls (P = 0.009 and P = 0.02). CONCLUSIONS An increased frequency of MBL2 genotypes associated with low MBL levels was observed in Euro-derived patients, suggesting a potential role for MBL in the susceptibility to HIV-1 infection in Euro-derived individuals.

Objective: This study aimed to investigate the association between 4 polymorphisms in the leptin, leptin receptor, and adiponectin (APMI) genes and the occurrence of lipodystrophy and dyslipidemia in HIV-infected patients receiving highly active antiretroviral therapy (HAART). Materials and Methods: Genotypes of 410 HIV-infected patients on HAART were investigated. Anthropometric (weight, height, waist circumference and skinfolds thickness) and biochemical (blood lipids, glucose, leptin, and adiponectin levels) parameters were evaluated. Genotype frequencies were compared between patients with or without lipodystrophy. Mean biochemical and anthropometric parameters were compared between the different genotypes. Results: Lipodystrophy prevalence was 53.4%. Genotype frequencies were not different between patients with or without lipodystrophy. Carriers of the A allele for the APMI-11391 G>A and of the C allele for APM1-11377 C>G presented higher adiponectin levels compared to other genotypes, and carriers of the -11391A-11377C haplotype when compared with carriers of other haplotypes. Conclusions: SNPs in APM1 gene are associated with adiponectin levels in HIV-infected patients receiving HAART and may thus affect the occurrence of metabolic alterations in these patients. No influence of the leptin and leptin receptor gene polymorphisms on the occurrence of lipodystrophy and dyslipidemia was observed.

Expanded access to antiretroviral therapy (ART) offers opportunities to strengthen HIV prevention in resource-limited settings. We invited 27 ART programmes from urban settings in Africa, Asia and South America to participate in a survey, with the aim to examine what preventive services had been integrated in ART programmes. Twenty-two programmes participated; eight (36%) from South Africa, two from Brazil, two from Zambia and one each from Argentina, India, Thailand, Botswana, Ivory Coast, Malawi, Morocco, Uganda and Zimbabwe and one occupational programme of a brewery company included five countries (Nigeria, Republic of Congo, Democratic Republic of Congo, Rwanda and Burundi). Twenty-one sites (96%) provided health education and social support, and 18 (82%) provided HIV testing and counselling. All sites encouraged disclosure of HIV infection to spouses and partners, but only 11 (50%) had a protocol for partner notification. Twenty-one sites (96%) supplied male condoms, seven (32%) female condoms and 20 (91%) provided prophylactic ART for the prevention of mother-to child transmission. Seven sites (33%) regularly screened for sexually transmitted infections (STI). Twelve sites (55%) were involved in activities aimed at women or adolescents, and 10 sites (46%) in activities aimed at serodiscordant couples. Stigma and discrimination, gender roles and funding constraints were perceived as the main obstacles to effective prevention in ART programmes. We conclude that preventive services in ART programmes in lower income countries focus on health education and the provision of social support and male condoms. Strategies that might be equally or more important in this setting, including partner notification, prompt diagnosis and treatment of STI and reduction of stigma in the community, have not been implemented widely.

Objectives: We assessed mortality associated with immunologic and virologic patterns of response at 6 months of highly active antiretroviral therapy (HAART) in HIV-infected individuals from resource-limited countries in Africa and South America. Methods: Patients who initiated HAART between 1996 and 2007, aged 16 years or older, and had at least 1 measurement (HIV-1 RNA plasma viral load or CD4 cell count) at 6 months of therapy (3-9 month window) were included. Therapy response was categorized as complete, discordant (virologic only or immunologic only), and absent. Associations between 6-month response to therapy and all-cause mortality were assessed by Cox proportional hazards regression. Robust standard errors were calculated to account for intrasite correlation. Results: A total of 7160 patients, corresponding to 15,107 person-years, were analyzed. In multivariable analysis adjusted for age at HAART initiation, baseline clinical stage and CD4 cell count, year of HAART initiation, clinic, occurrence of an AIDS-defining condition within the first 6 months of treatment, and discordant and absent responses were associated with increased risk of death. Conclusions: Similar to reports from high-income countries, discordant immunologic and virologic responses were associated with intermediate risk of death compared with complete and no response in this large cohort of HIV-1 patients from resource-limited countries. Our results support a recommendation for wider availability of plasma viral load testing to monitor antiretroviral therapy in these settings.

Infection with drug-resistant human immunodeficiency virus type 1 (HIV-1) has been documented in all countries that have surveyed for it and may result in an unfavorable response to therapy. The prevalence and characteristics of individuals with transmitted resistance to antiretroviral drugs have been scarcely described in Brazil. We performed antiretroviral resistance testing prior to initiation of therapy in 400 subjects enrolled from 20 centers in 13 Brazilian cities between March and September 2007. Genotyping was conducted using PCR-amplified HIV pol products by automated sequencing, and genotype interpretation was done according to the IAS-USA consensus. Of 400 eligible participants, 387 (95.8%) were successfully tested. Seven percent of antiretroviral-naive patients carried viruses with one or more major mutation associated with drug resistance. The prevalence of these mutations was 1.0% for protease inhibitors, 4.4% for nonnucleoside reverse transcriptase inhibitors, and 1.3% for nucleoside reverse transcriptase inhibitors. The frequency of multidrug resistance among the resistant strains was 13.6%. Among subjects infected with drug-resistant virus, the majority were infected with subtype B viruses (91%). Subjects from the city of Sao Paulo had higher transmitted resistance mutations compared to the rest of the country. Reporting a partner taking antiretroviral medications was associated with a higher chance of harboring HIV variants with major drug resistance mutations [odds ratio = 2.57 (95% confidence interval, 1.07-6.16); p = 0.014]. Resistance testing in drug-naive individuals identified 7% of subjects with mutations associated with reduced susceptibility to antiretroviral drugs. Continued surveillance of drug-resistant HIV-1 in Brazil is warranted when guidelines for HIV prophylaxis and treatment are updated. Resistance testing among drug-naive patients prior to treatment initiation should be considered, mainly directed at subjects whose partners are already on antiretroviral therapy.

To examine the accuracy of the World Health Organization immunological criteria for virological failure of antiretroviral treatment.Analysis of 10 treatment programmes in Africa and South America that monitor both CD4 cell counts and HIV-1 viral load. Adult patients with at least two CD4 counts and viral load measurements between month 6 and 18 after starting a non-nucleoside reverse transcriptase inhibitor-based regimen were included. WHO immunological criteria include CD4 counts persistently100 cells/microl, a fall below the baseline CD4 count, or a fall of50% from the peak value. Virological failure was defined as two measurementsor =10 0000 copies/ml (higher threshold) oror =500 copies/ml (lower threshold). Measures of accuracy with exact binomial 95% confidence intervals (CI) were calculated.A total of 2009 patients were included. During 1856 person-years of follow up 63 patients met the immunological criteria and 35 patients (higher threshold) and 95 patients (lower threshold) met the virological criteria. Sensitivity [95% confidence interval (CI)] was 17.1% (6.6-33.6%) for the higher and 12.6% (6.7-21.0%) for the lower threshold. Corresponding results for specificity were 97.1% (96.3-97.8%) and 97.3% (96.5-98.0%), for positive predictive value 9.5% (3.6-19.6%) and 19.0% (10.2-30.9%) and for negative predictive value 98.5% (97.9-99.0%) and 95.7% (94.7-96.6%).The positive predictive value of the WHO immunological criteria for virological failure of antiretroviral treatment in resource-limited settings is poor, but the negative predictive value is high. Immunological criteria are more appropriate for ruling out than for ruling in virological failure in resource-limited settings.

International audience; BACKGROUND: In high-income countries, viral load is routinely measured to detect failure of antiretroviral therapy (ART) and guide switching to second-line ART. Viral load monitoring is not generally available in resource-limited settings. We examined switching from nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line regimens to protease inhibitor-based regimens in Africa, South America and Asia. DESIGN AND METHODS: Multicohort study of 17 ART programmes. All sites monitored CD4 cell count and had access to second-line ART and 10 sites monitored viral load. We compared times to switching, CD4 cell counts at switching and obtained adjusted hazard ratios for switching (aHRs) with 95% confidence intervals (CIs) from random-effects Weibull models. RESULTS: A total of 20 113 patients, including 6369 (31.7%) patients from 10 programmes with access to viral load monitoring, were analysed; 576 patients (2.9%) switched. Low CD4 cell counts at ART initiation were associated with switching in all programmes. Median time to switching was 16.3 months [interquartile range (IQR) 10.1-26.6] in programmes with viral load monitoring and 21.8 months (IQR 14.0-21.8) in programmes without viral load monitoring (P < 0.001). Median CD4 cell counts at switching were 161 cells/microl (IQR 77-265) in programmes with viral load monitoring and 102 cells/microl (44-181) in programmes without viral load monitoring (P < 0.001). Switching was more common in programmes with viral load monitoring during months 7-18 after starting ART (aHR 1.38; 95% CI 0.97-1.98), similar during months 19-30 (aHR 0.97; 95% CI 0.58-1.60) and less common during months 31-42 (aHR 0.29; 95% CI 0.11-0.79). CONCLUSION: In resource-limited settings, switching to second-line regimens tends to occur earlier and at higher CD4 cell counts in ART programmes with viral load monitoring compared with programmes without viral load monitoring.

One of the most recent phenomena related to the acquired immunodeficiency syndrome (AIDS) is the emergence of a new vulnerable population: the elderly. One of the factors that account for this increase is the development of combination antiretroviral therapy (ART), which has provided better quality of life and life expectancy for HIV-positive patients. However, ART is associated with adverse effects such as dyslipidemia, diabetes mellitus and insulin resistance, which are risk factors for cardiovascular disease. Due to the impact of ART on lipid and glucose metabolism, many studies were published involving HIV infection and cardiovascular disease, as well as their risk factors and the use of ART, but few of them reported on the cardiotoxicity of this therapy in the elderly. The objective of this study is to review the main metabolic changes caused by the use of antiretroviral therapy and its impact on an increased risk of cardiovascular disease in elderly people with HIV.

Objectif Analyser la perte précoce de patients par les programmes de traitement antirétroviral (ART) dans les pays à ressources limitées. Méthodes A partir des données concernant 5491 patients adultes débutant un traitement ART (âge médian : 35 ans, 46 % de femmes), dans le cadre de 15 programmes de traitement en Afrique, en Asie et en Amérique du Sud comprenant un suivi de 12 mois et plus, nous avons étudié les facteurs d’absence de suivi après le début du traitement et les nombres de perdus pour le suivi et de décès au cours des 6 premiers mois. Résultats Globalement, 211 patients (3,8 %) n’ont pas eu de suivi, 880 (16,0 %) ont été perdus pour le suivi et 141 (2,6 %) sont décédés, à la connaissance du programme, dans les 6 premiers mois. La probabilité d’une absence de suivi était plus élevée pendant la période 2003-2004 qu’en 2000 ou dans les années antérieures (odds ratio, OR : 5,06 ; intervalle de confiance à 95 %, IC : 1,28-20,0) et il en était de même pour les perdus pour le suivi (ratio de danger, RD : 7,62 ; IC à 95 % : 4,55-12,8), mais pas pour le nombre de décès enregistrés (RD : 1,02 ; IC à 95 % : 0,44-2,36). Par rapport à une numération des CD4 de référence 50 cellules/μl, une numération 25 cellules/μl était associée à une plus forte probabilité d’absence de suivi (OR : 2,49 ; IC à 95 % : 1,43-4,33), de perte pour le suivi (RD : 1,48 ; IC à 95 % : 1,23-1,77) et de décès (RD : 3,34 ; IC à 95 % : 2,10-5,30). Par rapport à un traitement gratuit, les programmes fonctionnant avec une tarification à l’acte était associés à une plus grande probabilité d’absence de suivi (OR : 3,71 ; IC à 95 % : 0,97-16,05) et à une plus forte mortalité (RD : 4,64 ; IC à 95 % : 1,11-19,41). Conclusion Les pertes précoces de patients sont devenues de plus en plus courantes avec l’élargissement des programmes et sont associées à la tarification à l’acte et à une immunodéficience avancée au départ du traitement. Des mesures pour augmenter au maximum la rétention des patients dans les programmes ART sont nécessaires dans les pays à faibles ressources. Objective To analyse the early loss of patients to antiretroviral therapy (ART) programmes in resource-limited settings. Methods Using data on 5491 adult patients starting ART (median age 35 years, 46% female) in 15 treatment programmes in Africa, Asia and South America with ≥ 12 months of follow-up, we investigated risk factors for no follow-up after treatment initiation, and loss to follow-up or death in the first 6 months. Findings Overall, 211 patients (3.8%) had no follow-up, 880 (16.0%) were lost to follow-up and 141 (2.6%) were known to have died in the first 6 months. The probability of no follow-up was higher in 2003–2004 than in 2000 or earlier (odds ratio, OR: 5.06; 95% confidence interval, CI: 1.28–20.0), as was loss to follow-up (hazard ratio, HR: 7.62; 95% CI: 4.55–12.8) but not recorded death (HR: 1.02; 95% CI: 0.44–2.36). Compared with a baseline CD4-cell count ≥ 50 cells/μl, a count < 25 cells/μl was associated with a higher probability of no follow-up (OR: 2.49; 95% CI: 1.43–4.33), loss to follow-up (HR: 1.48; 95% CI: 1.23–1.77) and death (HR: 3.34; 95% CI: 2.10–5.30). Compared to free treatment, fee-for-service programmes were associated with a higher probability of no follow-up (OR: 3.71; 95% CI: 0.97–16.05) and higher mortality (HR: 4.64; 95% CI: 1.11–19.41). Conclusion Early patient losses were increasingly common when programmes were scaled up and were associated with a fee for service and advanced immunodeficiency at baseline. Measures to maximize ART programme retention are required in resource-poor countries. Objetivo Analizar la pérdida temprana de pacientes para el seguimiento en los programas de tratamiento antirretroviral (TAR) aplicados en entornos con recursos limitados. Métodos A partir de los datos de 5491 pacientes adultos que comenzaron el TAR (mediana de la edad: 35 años, mujeres en el 46% de los casos) en 15 programas de tratamiento en África, Asia y América del Sur con al menos 12 meses de seguimiento, investigamos los factores de riesgo de seguimiento nulo tras el inicio del tratamiento, y de pérdida para el seguimiento o defunción durante los 6 primeros meses. Resultados Globalmente, 211 pacientes (3,8%) no fueron objeto de seguimiento alguno, 880 (16,0%) fueron perdidos para el seguimiento y 141 (2,6%) murieron antes de transcurridos seis meses. La probabilidad de seguimiento nulo fue mayor en 2003–2004 que en 2000 o en años anteriores (razón de posibilidades [odds ratio, OR]: 5,06; intervalo de confianza (IC) del 95%, IC95%: 1,28–20,0), al igual que la pérdida para el seguimiento (cociente de riesgos instantáneos [hazard ratio, HR]: 7,62; IC95%: 4,55–12,8), pero no así la mortalidad registrada (HR: 1,02; IC95%: 0,44–2,36). En comparación con un recuento de CD4 ≥ 50 células/μl al comienzo del estudio, un recuento < 25 células/μl se asoció a una probabilidad mayor de seguimiento nulo (OR: 2,49; IC95%: 1,43–4,33), de pérdida para el seguimiento (HR: 1,48; IC95%: 1,23–1,77) y de defunción (HR: 3,34; IC95%: 2,10–5,30). Comparados con el tratamiento gratuito, los programas con cobro de honorarios por servicios prestados se asociaron a un aumento de la probabilidad de seguimiento nulo (OR: 3,71; IC95%: 0,97–16,05) y a una mayor mortalidad (HR: 4,64; IC95%: 1,11–19,41). Conclusión Las pérdidas tempranas de pacientes para el seguimiento fueron más frecuentes cuando los programas se expandieron, y se asociaron al cobro de honorarios por servicios prestados y a una inmunodeficiencia avanzada al inicio del estudio. Se deben tomar medidas para optimizar la retención de los pacientes en los programas de TAR en los países con recursos escasos.

The aim of the study was to evaluate the possibility of using lopinavir/ritonavir (LPV/RTV) alone as maintenance therapy in HIV-infected individuals with virological suppression. This was a single-armed single-centre pilot trial. Asymptomatic HIV-infected patients on highly active antiretroviral therapy (HAART) including LPV/RTV and with plasma HIV RNA less than 40 copies/mL for at least 6 months were enrolled in the study during which they continued with LPV/RTV alone. The intention was to recruit 25 patients to be followed for 2 years. Viral failure was defined as two consecutive HIV RNA measurements greater than 40 copies/mL. Nadir and baseline CD4 cell counts highest ever HIV RNA load time with undetectable viraemia before monotherapy number of previous antiretroviral (ARV) regimens and gene polymorphism at CYP3A4 and CYP3A5 were evaluated. All patients (27) completed the study. Their median age was 43 years and 66% were men. Ten patients (37%) failed to maintain virological suppression (the median time to HIV rebound was 10.5 months with a range of 4-23 months). One patient developed full resistance to LPV and another developed neurocognitive impairment while on LPV/RTV which improved after HAART reintroduction. There were no differences between failures and nonfailures according to the analysed parameters. Patients with viral failure were successfully resuppressed. LPV/RTV maintenance therapy was associated with 37% failure a higher than expected failure rate. In order to ensure that unnecessary risks are not being taken in patients on LPV/RTV this finding should be further evaluated in large randomized trials for longer periods of follow-up. (authors)

The objective of this article is to assess the knowledge about HIV/aids in middle aged acquaintance group participants from the Vale do Sinos, Rio Grande do Sul State, Brazil. A prospective cross-sectional study with 168 individuals (9.5% male and 90.5% female) between 40 and 59 years of age was performed. A questionnaire comprising questions about the concept, transmission, vulnerability, prevention, and treatment domains on HIV issues was constructed. It was observed that 61.3% of the sample had finished elementary education and 45.2% had a monthly income ranging from 1 to 3 minimum wages. In the conceptual domain, 65.2% did not know that HIV infection has an asymptomatic phase and 34.5% believed HIV could be transmitted by a mosquito bite. In prevention and vulnerability domains, 19.5% had no knowledge about female condoms and 29.2% believed that the disease was confined to specific groups. Regarding to antiretroviral treatment, 12.5% had no idea about its existence. According to findings, middle aged participants from acquaintance groups in Vale do Sinos had misconceptions about HIV/aids which might enhance the risk of infection. Therefore it is necessary to provide public health programs directed to this population group in order to prevent or decrease the risk of HIV transmission.

Background: To evaluate the impact of HIV-1 CRF31_BC in the southern Brazilian HIV epidemic. Methods: Blood plasma from 284 patients was collected from July 2002 to January 2003 at 2 reference HIV/AIDS centers in southern Brazil. Viral protease and reverse transcriptase (RT) genomic regions were amplified by RT polymerase chain reaction, sequenced, and subtyped. Evolutionary analyses were performed to estimate the CRF31_BC most recent common ancestor and its population growth rate with BEAST version 1.3. Results: CRF31_BC was responsible for 7.4% of infections. The average time of HIV diagnosis and the proportion of patients on antiretroviral treatment were shorter for CRF31_BC and subtype C than for subtype B. CRF31_BC was found as early as in 1990 in the Brazilian epidemic. Evolutionary analysis of CRF31_BC revealed that it appeared immediately after the introduction of subtype C in Brazil and has been growing at a similar rate as subtype C. Conclusions: CRF31_BC plays an important role in the HIV epidemic of southern Brazil, and its prevalence has increased throughout the years. This circulating recombinant form corresponds to approximately 25% of total HIV isolates in this region in 2004. Understanding the cause of this spread is important for public health strategies in Brazil and in Latin America.

BACKGROUND: Subtype C is the most prevalent HIV-1 subtype in the world, mainly in countries with the highest HIV prevalence. However, few studies have evaluated the impact of antiretroviral therapy on this subtype. In southern Brazil, the first developing country to offer free and universal treatment, subtypes B and C co-circulate with equal prevalence, allowing for an extensive evaluation of this issue. METHODS AND FINDINGS: Viral RNA of 160 HIV-1+ patients was extracted, and the protease and reverse transcriptase genes were sequenced, subtyped and analyzed for ARV mutations. Sequences were grouped by subtype, and matched to type (PI, NRTI and NNRTI) and time of ARV exposure. Statistical analyses were performed to compare differences in the frequency of ARV-associated mutations. There were no significant differences in time of treatment between subtypes B and C groups, although they showed distinct proportions of resistant strains at different intervals for two of three ARV classes. For PI, 26% of subtype B strains were resistant, compared to only 8% in subtype C (p = 0.0288, Fisher's exact test). For NRTI, 54% of subtype B strains were resistant versus 23% of subtype C (p = 0.0012). Differences were significant from 4 years of exposure, and remained so until the last time point analyzed. The differences observed between both subtypes were independent of time under rebound viremia in cases of virologic failure and of the number of HAART regimens used by treated patients. CONCLUSIONS: Our results pointed out to a lower rate of accumulation of mutations conferring resistance to ARV in subtype C than in subtype B. These findings are of crucial importance for current initiatives of ARV therapy roll-out in developing countries, where subtype is C prevalent.

OBJECTIVES: To assess the frequency of and risk factors for discordant responses at 6 months on highly active antiretroviral therapy (HAART) in previously treatment-naive HIV patients from resource-limited countries. METHODS: The Antiretroviral Therapy in Low-Income Countries Collaboration is a network of clinics providing care and treatment to HIV-infected patients in Africa, Latin America, and Asia. Patients who initiated therapy between 1996 and 2004, were aged 16 years or older, and had a baseline CD4 cell count were included in this analysis. Responses were defined based on plasma viral load (PVL) and CD4 cell count at 6 months as complete virologic and immunologic (VR(+)IR(+)), virologic only (VR(+)IR(-)), immunologic only (VR(-)IR(+)), and nonresponse (VR(-)IR(-)). Multinomial logistic regression was used to assess the association between therapy responses and clinical and demographic variables. RESULTS: Of the 3111 patients eligible for analysis, 1914 had available information at 6 months of therapy: 1074 (56.1%) were VR(+)IR(+), 364 (19.0%) were VR(+)IR(-), 283 (14.8%) were (VR(-)IR(+)), and 193 (10.1%) were VR(-)IR(-). OF THE 3111 patients eligible for analysis, 1914 had available information at 6 months of therapy: 1074 (56.1%) were VRIR, 364 (19.0%) were VRIR, 283 (14.8%) were (VRIR), and 193 (10.1%) were VRIR. Compared with complete responders, virologic-only responders were older, had a higher baseline CD4 cell count, had a lower baseline PVL, and were more likely to have received a nonstandard HAART regimen; immunologic-only responders were younger, had a lower baseline CD4 cell count, had a higher baseline PVL, and were more likely to have received a protease inhibitor-based regimen. CONCLUSIONS: The frequency of and risk factors for discordant responses were comparable to those observed in developed countries. Longer follow-up is needed to assess the long-term impact of discordant responses on mortality in these resource-limited settings.

The objective of this study was to assess the knowledge about HIV/AIDS in participants of companionship groups in the Vale do Sinos, Rio Grande do Sul, Brazil. It was a prospective cross-sectional study in a sample of 510 individuals, 17% males and 82.5% females aged between 60 and 90 years. We used the Questionnaire on HIV for the Old Aged, which comprises the general characteristics of the participants and questions concerning HIV/AIDS, organized into the elements 'concept', 'transmission', 'prevention', 'vulnerability', and 'treatment'. Nearly half of the participants (48.4 %) reported having studied 4 to 7 years and the monthly income of 52.2% was of 1 to 3 minimum wages. In the dimensions concept and transmission, 49.4% had no idea about the asymptomatic phase of the infection, and 41.4% believed HIV could be transmitted by a mosquito bite. With regard to prevention and vulnerability, 25.5% did not know about the female condom and 36.9% considered AIDS a disease confined to men who have sex with men, sex workers, and injection-drug users. Regarding antiretroviral treatment, 12.2% ignored its existence. Elderly people in companionship groups have important misconceptions about HIV/AIDS, which can increase their risk of infection. There is a need for public health programs directed to this population in order to prevent or decrease the risk of HIV transmission.