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Walter Dehority,1 Rolando M Viani2 1Department of Pediatrics, Division of Infectious Diseases, The University of New Mexico Health Sciences Center, University of New Mexico, Albuquerque, NM, USA; 2Department of Pediatrics, Division of Infectious Diseases, Center for AIDS Research, University of California, San Diego School of Medicine, Rady Children's Hospital, San Diego, CA, USA Abstract: Etravirine is a non-nucleoside reverse transcriptase inhibitor now licensed for treatment of human immunodeficiency virus (HIV)-1 infection in both children over 6 years of age and adults. Etravirine demonstrates a high genetic barrier to the development of resistance, as multiple mutations are typically required prior to the onset of reduced susceptibility to the drug. It retains in vitro and clinical activity against many HIV-1 isolates, demonstrating resistance to other non-nucleoside reverse transcriptase inhibitors, such as efavirenz and nevirapine. Given the ability of HIV to develop resistance rapidly across the non-nucleoside reverse transcriptase inhibitor class of antiretrovirals, etravirine has a welcome place in the management of HIV-infected patients, particularly treatment-experienced individuals harboring non-nucleoside reverse transcriptase inhibitor mutations. Etravirine has been shown to improve CD4 counts and viral load significantly in HIV-infected adults on combination antiretroviral therapy when compared with placebo in a large, randomized controlled trial. Data on the utility of etravirine in children are still somewhat limited, although a recent pediatric trial has demonstrated adequate pharmacokinetics, safety, and efficacy of etravirine in a small number of HIV-infected children and adolescents. In both children and adults, rash appears to be the most common adverse effect described. Despite its high genetic barrier to resistance, evidence of mutations conferring etravirine resistance has been documented in both adult and pediatric patients. Such mutations have been best described in treatment-experienced populations, including those who have never been exposed to the drug. This review describes the existing literature on the use of etravirine in the pediatric population, and highlights future and ongoing directions of investigation. Keywords: etravirine, pediatric, human immunodeficiency virus, antiretrovirals, non-nucleoside reverse transcriptase inhibitor

The aim of this study was to evaluate the performance of the rapid antibody test Determine(R) HIV-1/2, in pregnant women at Tijuana General Hospital. Pregnant women seeking prenatal care or admitted in labour had blood drawn for a rapid HIV test (Determine(R) HIV-1/2), enzyme immunoassay (EIA) and Western blot. Between March and November 2003, 1068 women in labour and 1529 women in prenatal care were enrolled. The sensitivity, specificity, positive and negative predictive values were 100%, 99.8%, 77% and 100%, respectively. For women in labour, the mean time between blood collection and rapid test results was 92 minutes (range: 20-205 minutes) compared with 41 hours (range 24-120 hours) for HIV EIA (P = 0.012). All HIV-exposed infants received oral zidovudine. These findings indicate that the rapid test Determine(R) HIV-1/2 has a high sensitivity and specificity in pregnant women. Rapid HIV testing greatly diminishes the time to diagnosis and enables prompt intervention with antiretrovirals at delivery. [ABSTRACT FROM AUTHOR]

This study examined the prevalence of primary human immunodeficiency type 1 (HIV-1) drug resistance among recently infected youth in the United States. Of the 55 subjects studied, major mutations conferring HIV drug resistance were present in 10 (18%). Eight (15%) had nonnucleoside reverse-transcriptase inhibitor (NNRTI) mutations, with the majority (6) having the K103N mutation; 2 (4%) had nucleoside reverse-transcriptase inhibitor (NRTI) mutations; and 2 (4%) had protease inhibitor (PI) mutations. Phenotypic drug resistance was present in 12 (22%) subjects: 10 (18%) for NNRTIs, 2 (4%) for NRTIs, and 3 (5.5%) for PIs. The prevalence of primary HIV-1 drug resistance, particularly to NNRTIs, in this group of recently infected youth was high. [ABSTRACT FROM AUTHOR]

Introduction: We assessed effects of AZD7442 (tixagevimab/cilgavimab) on deaths from any cause or hospitalizations due to coronavirus disease 2019 (COVID-19) and symptom severity and longer-term safety in the TACKLE adult outpatient treatment study., Methods: Participants received 600 mg AZD7442 (n = 452) or placebo (n = 451) ≤ 7 days of COVID-19 symptom onset., Results: Death from any cause or hospitalization for COVID-19 complications or sequelae through day 169 (key secondary endpoint) occurred in 20/399 (5.0%) participants receiving AZD7442 versus 40/407 (9.8%) receiving placebo [relative risk reduction (RRR) 49.1%; 95% confidence interval (CI) 14.5, 69.7; p = 0.009] or 50.7% (95% CI 17.5, 70.5; p = 0.006) after excluding participants unblinded before day 169 for consideration of vaccination). AZD7442 reduced progression of COVID-19 symptoms versus placebo through to day 29 (RRR 12.5%; 95% CI 0.5, 23.0) and improved most symptoms within 1-2 weeks. Over median safety follow-up of 170 days, adverse events occurred in 174 (38.5%) and 196 (43.5%) participants receiving AZD7442 or placebo, respectively. Cardiac serious adverse events occurred in two (0.4%) and three (0.7%) participants receiving AZD7442 or placebo, respectively., Conclusions: AZD7442 was well tolerated and reduced hospitalization and mortality through 6 months, and symptom burden through 29 days, in outpatients with mild-to-moderate COVID-19., Clinical Trial Registration: Clinicaltrials.gov, NCT04723394. ( https://beta., Clinicaltrials: gov/study/NCT04723394 )., (© 2023. The Author(s).)

Background: Early intramuscular administration of SARS-CoV-2-neutralising monoclonal antibody combination, tixagevimab-cilgavimab, to non-hospitalised adults with mild to moderate COVID-19 has potential to prevent disease progression. We aimed to evaluate the safety and efficacy of tixagevimab-cilgavimab in preventing progression to severe COVID-19 or death., Methods: TACKLE is an ongoing, phase 3, randomised, double-blind, placebo-controlled study conducted at 95 sites in the USA, Latin America, Europe, and Japan. Eligible participants were non-hospitalised adults aged 18 years or older with a laboratory-confirmed SARS-CoV-2 infection (determined by RT-PCR or an antigen test) from any respiratory tract specimen collected 3 days or less before enrolment and who had not received a COVID-19 vaccination. A WHO Clinical Progression Scale score from more than 1 to less than 4 was required for inclusion and participants had to receive the study drug 7 days or less from self-reported onset of mild to moderate COVID-19 symptoms or measured fever. Participants were randomly assigned (1:1) to receive either a single tixagevimab-cilgavimab 600 mg dose (two consecutive 3 mL intramuscular injections, one each of 300 mg tixagevimab and 300 mg cilgavimab) or placebo. Randomisation was stratified (using central blocked randomisation with randomly varying block sizes) by time from symptom onset, and high-risk versus low-risk of progression to severe COVID-19. Participants, investigators, and sponsor staff involved in the treatment or clinical evaluation and monitoring of the participants were masked to treatment-group assignments. The primary endpoints were severe COVID-19 or death from any cause through to day 29, and safety. This study is registered with ClinicalTrials.gov, NCT04723394., Findings: Between Jan 28, 2021, and July 22, 2021, 1014 participants were enrolled, of whom 910 were randomly assigned to a treatment group (456 to receive tixagevimab-cilgavimab and 454 to receive placebo). The mean age of participants was 46·1 years (SD 15·2). Severe COVID-19 or death occurred in 18 (4%) of 407 participants in the tixagevimab-cilgavimab group versus 37 (9%) of 415 participants in the placebo group (relative risk reduction 50·5% [95% CI 14·6-71·3]; p=0·0096). The absolute risk reduction was 4·5% (95% CI 1·1-8·0; p<0·0001). Adverse events occurred in 132 (29%) of 452 participants in the tixagevimab-cilgavimab group and 163 (36%) of 451 participants in the placebo group, and were mostly of mild or moderate severity. There were three COVID-19-reported deaths in the tixagevimab-cilgavimab group and six in the placebo group., Interpretation: A single intramuscular tixagevimab-cilgavimab dose provided statistically and clinically significant protection against progression to severe COVID-19 or death versus placebo in unvaccinated individuals and safety was favourable. Treating mild to moderate COVID-19 earlier in the disease course with tixagevimab-cilgavimab might lead to more favourable outcomes., Funding: AstraZeneca., Competing Interests: Declaration of interests HM has received consultation fees from AstraZeneca and is supported by the UK National Institute for Health Research's Comprehensive Biomedical Research Centre at University College London Hospitals. He has consulted for Millfield Medical Ltd on the development of a new continuous positive airway pressure machine. JASC reports serving on advisory boards for Pfizer and Eli Lilly; and serving on advisory boards and as a speaker for AstraZeneca and Roche. FDRH reports funding from AstraZeneca to cover meeting attendances and operationalisation of TACKLE in the UK as UK principal investigator. He has received funding by UK Research and Innovation and National Institute for Health and Care Research (NIHR) for national Urgent Public Health COVID-19 trials, and as Director of the NIHR Applied Research Collaboration, Oxford Thames Valley, and investigator on the Oxford Biomedical Research Centre and NIHR MedTech. FP has received personal fees and grants from Amgen, AstraZeneca, Boehringer Ingelheim, Ferrer, Kowa, Medix, Merck, Merck Sharp and Dohme, Novartis, Pfizer, Sanofi, Servier, and Silanes. KK has received research grants for the conduct of the TACKLE trial, reports funding from Regeneron, Eli Lilly, Merck, Pfizer, and Adagio, and serves as a speaker for Regeneron. DA, AT, SS, RHA, BHB, DB, PG, JJ, GCKWK, KWP, RMV, KS, VA, MNP, and MTE are employees of, and hold or may hold stock in, AstraZeneca., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Rezafungin (RZF) is a novel echinocandin exhibiting distinctive pharmacokinetics/pharmacodynamics. STRIVE was a phase 2, double-blind, randomized trial designed to compare the safety and efficacy of RZF once weekly (QWk) to caspofungin (CAS) once daily for treatment of candidemia and/or invasive candidiasis (IC)., Methods: Adults with systemic signs and mycological confirmation of candidemia and/or IC were randomized to RZF 400 mg QWk (400 mg), RZF 400 mg on week 1 then 200 mg QWk (400/200 mg), or CAS 70 mg as a loading dose followed by 50 mg daily for ≤4 weeks. Efficacy assessments included overall cure (resolution of signs of candidemia/IC + mycological eradication) at day 14 (primary endpoint), investigator-assessed clinical response at day 14, and 30-day all-cause mortality (ACM) (secondary endpoints), and time to negative blood culture. Safety was evaluated by adverse events and ACM through follow-up., Results: Of 207 patients enrolled, 183 were in the microbiological intent-to-treat population (~21% IC). Overall cure rates were 60.5% (46/76) for RZF 400 mg, 76.1% (35/46) for RZF 400/200 mg, and 67.2% (41/61) for CAS; investigator-assessed clinical cure rates were 69.7% (53/76), 80.4% (37/46), and 70.5% (43/61), respectively. In total, 30-day ACM was 15.8% for RZF 400 mg, 4.4% for RZF 400/200 mg, and 13.1% for CAS. Candidemia was cleared in 19.5 and 22.8 hours in RZF and CAS patients, respectively. No concerning safety trends were observed; ACM through follow-up was 15.2% (21/138) for RZF and 18.8% (13/69) for CAS., Conclusions: RZF was safe and efficacious in the treatment of candidemia and/or IC., Clinical Trials Registration: NCT02734862., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: P1093 is an ongoing phase I/II multicenter open-label study of dolutegravir plus an optimized background regimen in age-defined pediatric cohorts; here we report the long-term safety and virologic efficacy outcomes for the oldest cohort., Methods: The study enrolled human immunodeficiency virus type 1 (HIV-1)-infected treatment-experienced adolescents aged 12 to <18 years, with an HIV-1 RNA level ≥1000 copies/mL . Cumulative safety and HIV-1 RNA outcomes were assessed once the last enrolled participant reached 144 weeks of follow-up., Results: Among 23 adolescents enrolled, 16 remained in the study at least 144 weeks; the median follow-up was 153 weeks (range, 55-193 weeks). Dolutegravir was well tolerated, with grade 3 clinical adverse events in 5 participants, grade 3 laboratory abnormalities in 3, and grade 4 laboratory abnormalities in 1; none of the adverse events or abnormalities were judged to be treatment related. In an-intent-to-treat analysis, an HIV-1 RNA level <400 copies/mL at week 144 was achieved in 43% (10 of 23 participants; 95% confidence interval, 23.2%-65.5%); in addition, 35% (8 of 23; 16.4%-57.3%) had an HIV-1 RNA level <50 copies/mL. Nine participants (39%) discontinued study treatment before 144 weeks, but none because of adverse events or drug intolerance. All participants with sustained virologic control had excellent adherence; most who experienced virologic failure had adherence levels <90%. HIV-1 genotypic drug resistance testing was available at time of failure from 6 participants; 1 had evolution in integrase resistance with E138T, S147G, and R263K mutations at week 192 and phenotypic dolutegravir resistance of a 5.1-fold change., Conclusions: Dolutegravir plus an optimized background regimen seemed safe, well tolerated, and efficacious in this cohort of treatment-experienced HIV-1-infected adolescents. Adherence remains problematic in this population., Clinical Trials Registration: NCT01302847., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Treatment of patients coinfected with hepatitis C and human immunodeficiency viruses (HCV; HIV) requires careful consideration of potential drug-drug interactions between HCV direct-acting antiviral agents (DAA) and HIV antiretrovirals. Glecaprevir/pibrentasvir is a fixed-dose combination of an NS3/4A protease inhibitor and an NS5A inhibitor approved for the treatment of chronic HCV genotype 1-6 infection, including patients with HIV coinfection., Methods: A series of phase 1 studies was conducted to evaluate potential interactions of glecaprevir and pibrentasvir with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, abacavir/dolutegravir/lamivudine, raltegravir, rilpivirine, atazanavir/ritonavir, darunavir/ritonavir, lopinavir/ritonavir, or efavirenz/emtricitabine/tenofovir disoproxil fumarate. Pharmacokinetics of the antiretrovirals and DAAs were characterized when administered alone and in combination to quantify changes in systemic drug exposure., Results: Glecaprevir area under the curve increased >4-fold in the presence of ritonavir-boosted HIV protease inhibitors, while pibrentasvir concentrations were not significantly affected; elevations in alanine transaminase occurred in combination with atazanavir/ritonavir only. Exposures of glecaprevir and pibrentasvir may be significantly decreased by efavirenz. Coadministration with glecaprevir and pibrentasvir did not result in clinically significant changes in the exposure of any antiretroviral agents., Conclusions: Atazanavir is contraindicated with glecaprevir/pibrentasvir and use of boosted protease inhibitors or efavirenz is not recommended. No clinically significant interactions were observed with other studied antiretrovirals., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

In adults, treatment of hepatitis C virus (HCV) infection with ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) with or without dasabuvir (DSV) and ±ribavirin (RBV) results in high rates of sustained virologic response (SVR). However, these regimens have not been investigated in adolescents. This ongoing, open-label, phase 2/3 study evaluated the pharmacokinetics, safety, and efficacy of OBV/PTV/r+DSV±RBV treatment for 12 weeks in adolescents infected with HCV genotype (GT) 1 without cirrhosis (part 1) and the safety and efficacy of OBV/PTV/r±DSV±RBV treatment for 12 or 24 weeks in adolescents infected with GT1 or GT4 without cirrhosis or with compensated cirrhosis (parts 1 and 2). Patients were 12-17 years of age and treatment naive or interferon experienced. Treatment regimens were based on HCV GT and cirrhosis status. Endpoints were SVR at posttreatment week 12 (SVR12), adverse events (AEs), and pharmacokinetic parameters. Thirty-eight adolescents were enrolled, 66% were female patients, and 76% were White; 42%, 40%, and 18% of patients had HCV GT1a, GT1b, and GT4 infections, respectively. Median age was 15 years (range, 12-17 years), and 1 patient had cirrhosis. The SVR12 rate was 100% (38/38; 95% confidence interval [CI], 90.8%-100%). No treatment-emergent grade 3 or 4 laboratory abnormalities were reported. No serious AEs occurred on treatment, and no AEs led to study drug discontinuation. The most common AEs were headache (21%), fatigue (18%), nasopharyngitis (13%), pruritus (13%), and upper respiratory tract infection (11%). Intensive pharmacokinetic results showed OBV, PTV, DSV, and ritonavir drug exposures were comparable to those seen in adults. Conclusion: Treatment with OBV/PTV/r±DSV±RBV was well tolerated and highly efficacious in adolescents with HCV GT1 or GT4 infection.

Background: Once-daily glecaprevir coformulated with pibrentasvir (glecaprevir/pibrentasvir) demonstrated high rates of sustained virologic response 12 weeks after treatment (SVR12) in patients with hepatitis C virus (HCV) genotype 1-6 infection. This phase 3 study evaluated the efficacy and safety of glecaprevir/pibrentasvir in patients with chronic HCV genotype 1-6 and human immunodeficiency virus type 1 (HIV-1) coinfection, including patients with compensated cirrhosis., Methods: EXPEDITION-2 was a phase 3, multicenter, open-label study evaluating glecaprevir/pibrentasvir (300 mg/120 mg) in HCV genotype 1-6/HIV-1-coinfected adults without and with compensated cirrhosis for 8 and 12 weeks, respectively. Patients were either HCV treatment-naive or experienced with sofosbuvir, ribavirin, or interferon, and antiretroviral therapy (ART) naive or on a stable ART regimen. Treatment-experienced genotype 3-infected patients were excluded. The primary endpoint was the SVR12 rate., Results: In total, 153 patients were enrolled, including 16 (10%) with cirrhosis. The SVR12 rate was 98% (n = 150/153; 95% confidence interval, 95.8-100), with no virologic failures in 137 patients treated for 8 weeks. One genotype 3-infected patient with cirrhosis had on-treatment virologic failure. Most adverse events were mild in severity; 4 patients (2.6%) had serious adverse events, all deemed unrelated to glecaprevir/pibrentasvir. Treatment discontinuation was rare (<1%). All patients treated with ART maintained HIV-1 suppression (<200 copies/mL) during treatment., Conclusions: Glecaprevir/pibrentasvir for 8 weeks in noncirrhotic and 12 weeks in cirrhotic patients is a highly efficacious and well-tolerated treatment for HCV/HIV-1 coinfection, regardless of baseline HCV load or prior treatment with interferon or sofosbuvir., Clinical Trial Registration: NCT02738138.

Objective: An estimated 336 per 100 000 people in Russia are infected with hepatitis C virus, including up to 75% with genotype (GT) 1b. In the TURQUOISE-II/-III trials, a 12-week regimen of the direct-acting antiviral agents ombitasvir (OBV), paritaprevir (PTV), ritonavir, and dasabuvir (DSV) in GT1b-infected patients with compensated cirrhosis resulted in 12-week sustained virologic response (SVR) rates of 100%., Patients and Methods: In TURQUOISE-IV, GT1b-infected patients (n=36) from Russia and Belarus with compensated cirrhosis, who were treatment naive or previously treated with pegylated interferon/ribavirin (RBV), received OBV/PTV/ritonavir+DSV+RBV for 12 weeks. The primary efficacy end point was SVR at 12 weeks. Safety assessments included adverse event (AE) monitoring and laboratory testing., Results: At baseline, patients had Child-Pugh scores of 5 (92%) or 6 (8%). Overall, 69% were treatment experienced (44% prior null responders, 32% relapsers, and 16% partial responders). All patients achieved SVR at 12 weeks (36/36; 100%). No patient experienced a serious AE or discontinued treatment prematurely. Treatment-emergent AEs possibly related to study drugs occurring in greater than or equal to 10% of patients were asthenia (19%), anemia (14%), cough (14%), and headache (11%); most events were mild in severity. Clinically significant laboratory abnormalities were infrequent., Conclusion: In Russian and Belarusian patients with hepatitis C GT1b infection and compensated cirrhosis, 100% achieved SVR at 12 weeks after 12 weeks' treatment with OBV/PTV/ritonavir+DSV+RBV. The treatment was well tolerated.

Background: Data on pediatric HIV in Peru are limited. The National Institute of Child Health (Instituto Nacional de Salud del Niño: INSN) cares for the most HIV-infected children under the age of 18 years in the country. We describe the outcomes of children seen at INSN's HIV clinic over the 10 years when antiretroviral therapy and prevention of mother-to-child transmission (PMTCT) interventions became available in 2004., Methods: We conducted a retrospective review of INSN HIV clinic patients between 2003 and 2012. Deidentified data were collected and analyzed., Results: A total of 280 children were included: 50.0% (140/280) were male; 80.0% (224/280) lived in metropolitan Lima. Perinatal transmission was the mode of HIV infection in 91.4% (256/280) of children. Only 17% (32/191) of mothers were known to be HIV-infected at delivery; of these mothers, 41% (13/32) were receiving antiretroviral therapy at delivery, 72% (23/32) delivered by Cesarean section and 47% (15/32) of their infants received antiretroviral prophylaxis. Median age at HIV diagnosis for all children was 35.7 months (interquartile range 14.5-76.8 months), and 67% (143/213) had advanced disease (clinical stage C). After HIV diagnosis, the most frequent hospitalization discharge diagnoses were bacterial pneumonia, chronic malnutrition, diarrhea, anemia and tuberculosis. Twenty-four patients (8.6%) died at a median age of 77.4 months., Conclusions: Most cases of pediatric HIV were acquired via perinatal transmission; few mothers were diagnosed before delivery; and among mothers with known HIV status, PMTCT was suboptimal even after national PMTCT policy was implemented. Most children were diagnosed with advanced disease. These findings underscore the need for improving early pediatric HIV diagnosis and treatment, as well as PMTCT strategies.

Glecaprevir (GLE) and pibrentasvir (PIB) are direct-acting antivirals coformulated as a combination tablet for once-daily treatment of chronic hepatitis C virus infection. The objective of this study was to evaluate the effect of different methods of tablet manipulations-cutting in half, grinding into powder, or crushing-on the bioavailability of GLE and PIB relative to whole film-coated bilayer tablets. This was a phase 1, single-dose, open-label, randomized, 5-period, nonfasting crossover study in 25 healthy adult male and female subjects. Intensive pharmacokinetic measurements were carried out up to 48 h after dosing on day 1 of each period. Safety and tolerability was assessed throughout the study. Compared with the reference whole tablets, cutting into half had minimal impact on GLE and PIB exposures (≤15% difference), whereas grinding or crushing the tablets resulted in lower exposures (27% to 61%) for GLE and higher exposures (21% to 83%) for PIB. These results provide guidance on appropriate administration of GLE/PIB in patients who have difficulty swallowing whole tablets., (Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: Despite recommendations for disclosure of HIV status to children living with HIV (CLHIV), fewer than half of CLHIV at the Instituto Nacional de Salud del Niño (INSN) in Lima, Peru, have had disclosure. How and when the disclosure process for CLHIV should take place in Peru has not been studied., Methods: We conducted a qualitative study at INSN to explore perceptions and experiences of 6 health care providers (HCPs), 14 disclosed and nondisclosed CLHIV (8-17 years), and their 14 caregivers regarding knowledge of illness, disclosure of HIV status, and appropriate disclosure approaches., Results: Disclosed children wanted to be told their diagnosis earlier. Nondisclosed children expressed frustration taking medications. Caregivers and HCPs discussed motivations to disclose, including educating, honesty, improving medication adherence, and preventing secondary transmission., Conclusion: Culturally appropriate guidelines and training for HCPs and caregivers are needed to support disclosure of children's HIV status and ongoing support for CLHIV.

Background: Diagnosis of latent tuberculosis infection (LTBI) is facilitated by tuberculin skin testing (TST) or interferon-gamma release assays such as the QuantiFERON TB Gold In-Tube (QTF-GIT) assays. Limited data exist on the utility of interferon-gamma release assays in HIV-infected children, which may be falsely negative due to immunosuppression., Methods: A cross-sectional study comparing TST to QTF-GIT for the diagnosis of suspected LTBI was performed in children in Tijuana, Mexico, and in San Diego, California. Concordance between TST (≥5 mm for HIV infected and ≥10 mm for HIV uninfected) and QTF-GIT was evaluated utilizing kappa coefficients. Multivariate logistic regression assessed factors influencing the results., Results: One hundred sixty-five children (70 HIV infected and 95 HIV uninfected) were evaluated (median age, 8.0 years). Among HIV-infected children, the median CD4 cell count was 913 cells/μL, with 92.9% of subjects on antiretroviral treatment and 80.0% with an HIV RNA load <400 copies/mL (76% <50 copies/mL). Among HIV-infected children with no history of tuberculosis, 12 HIV had either a positive QTF-GIT or TST ≥ 5 mm or both, giving a suspected LTBI prevalence of 20.3% (compared with 61.3% among HIV-uninfected children). Moderate concordance was demonstrated in HIV-infected children (both tests positive, κ = 0.42; 95% confidence interval: 8.9%-75.4%) and HIV-uninfected children (both tests positive, κ = 0.59; 95% confidence interval: 43.0%-76.5%)., Conclusions: A moderate correlation exists between TST and QTF-GIT among HIV-infected and uninfected children with preserved immune function in an area of moderate tuberculosis endemicity.

Background: Ombitasvir, paritaprevir with ritonavir, and dasabuvir (OBV/PTV/r ± DSV) ±ribavirin (RBV) are approved to treat hepatitis C virus (HCV) genotype 1 and 4 infection. Here, we investigate the safety and efficacy of OBV/PTV/r + DSV ±RBV for HCV genotype 1, and OBV/PTV/r + RBV for HCV genotype 4, in human immunodeficiency virus (HIV)-1 coinfected patients with or without compensated cirrhosis., Methods: TURQUOISE-I, Part 2 is a phase 3 multicenter study. Patients with or without cirrhosis were HCV treatment-naive or -experienced, on an HIV-1 antiretroviral regimen containing atazanavir, raltegravir, dolutegravir, or darunavir (for genotype 4 only), and had plasma HIV-1 ribonucleic acid <40 copies/mL at screening. Patients received OBV/PTV/r ± DSV ±RBV for 12 or 24 weeks., Results: In total, 228 patients were treated according to guidelines. Sustained virologic response at posttreatment week 12 (SVR12) was achieved by 194 of 200 (97%) and 27 of 28 (96%) patients with HCV genotype 1 and genotype 4 infection, respectively. There were 2 virologic failures: 1 breakthrough and 1 relapse in a cirrhotic and a noncirrhotic patient with genotype 1b and 1a infection, respectively. One reinfection occurred at posttreatment week 12 in a genotype 1a-infected patient. Excluding nonvirologic failures, the SVR12 rates were 98% (genotype 1) and 100% (genotype 4). Adverse events were mostly mild in severity and did not lead to discontinuation. Laboratory abnormalities were rare., Conclusions: The OBV/PTV/r ±DSV was well tolerated and yielded high SVR12 rates in patients with HCV genotype 1 or genotype 4/HIV-1 coinfection. The OBV/PTV/r ± DSV ±RBV is a potent HCV treatment option for patients with HIV-1 coinfection, regardless of treatment experience.

Background: Ombitasvir/paritaprevir/ritonavir with dasabuvir (OBV/PTV/r + DSV) ± ribavirin (RBV) is approved for hepatitis C virus (HCV) genotype 1 (GT1) treatment in HIV-1 coinfected patients. In healthy controls, coadministration of OBV/PTV/r + DSV + darunavir (DRV) lowered DRV trough concentration (Ctrough) levels. To assess the clinical significance of this change, TURQUOISE-I, Part 1b, evaluated the efficacy and safety of OBV/PTV/r + DSV + RBV in coinfected patients on stable, DRV-containing antiretroviral therapy (ART)., Methods: Patients were HCV treatment-naive or interferon-experienced, had CD4+ lymphocyte count ≥200 cells/µL or ≥14%, and plasma HIV-1 RNA suppression on once-daily (QD) DRV-containing ART at screening. Patients were randomized to maintain DRV 800 mg QD or switch to twice-daily (BID) DRV 600 mg; all received OBV/PTV/r + DSV + RBV for 12 weeks., Results: Twenty-two patients were enrolled and achieved SVR12. No adverse events led to discontinuation. Coadministration had minimal impact on DRV maximum observed plasma concentration and area under the curve; DRV Ctrough levels were slightly lower with DRV QD and BID. No patient experienced plasma HIV-1 RNA >200 copies/mL during treatment., Conclusions: HCV GT1/HIV-1 coinfected patients on stable DRV-containing ART achieved 100% SVR12 while maintaining plasma HIV-1 RNA suppression. Despite DRV exposure changes, episodes of intermittent HIV-1 viremia were infrequent., (© 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.)

The three-direct-acting antiviral (3D) regimen containing ombitasvir, paritaprevir, ritonavir, and dasabuvir with or without ribavirin (RBV) is approved for treatment of hepatitis C virus (HCV) genotype 1 (GT1)/human immunodeficiency virus type 1 (HIV-1) coinfection. Results of a pharmacokinetic substudy of 3D and darunavir are presented. HCV/HIV-1-coinfected subjects were randomized to maintain an antiretroviral regimen with darunavir at 800 mg once daily (QD) or switched to a regimen with darunavir at 600 mg twice daily (BID). On study day 1, subjects received 3D and RBV plus darunavir for 12 weeks. Pharmacokinetic parameters were compared for darunavir and ritonavir with and without 3D (week 4 and day -1). Pharmacokinetic parameters of 3D were compared to historical data. Ten subjects received darunavir QD, and 12 subjects received darunavir BID. The central value ratios (90% confidence interval [CI]) for maximum concentrations (C max ), area under the plasma concentration-time curve between 0 and 24 h postdose (AUC 24 ), and trough plasma concentration at 24 h postdose (C 24 ) of darunavir administered QD with 3D versus administration of darunavir alone were 0.92 (0.72, 1.18), 0.83 (0.71, 0.98), and 0.64 (0.44, 0.93), respectively. The ratios (90% CI) for darunavir C max , AUC 12 , and C 12 administered BID with 3D were 0.92 (0.76, 1.12), 0.88 (0.73, 1.05), and 0.73 (0.58, 0.92), respectively. Exposures of 3D were similar to or slightly lower than those in historical data. All darunavir trough concentrations (C trough ) associated with an HIV-1 RNA level of >40 copies/ml were above the darunavir 50% effective concentration (EC 50 ) of 550 ng/ml for resistant virus. In conclusion, the 3D regimen with darunavir QD or BID did not affect darunavir C max and AUC, whereas the darunavir C trough decreased. Changes in pharmacokinetic parameters of 3D were not considered clinically significant. Episodes of intermittent HIV-1 viremia were infrequent and were not associated with darunavir C trough values below 550 ng/ml. (This study has been registered at ClinicalTrials.gov under identifier NCT01939197.)., (Copyright © 2017 American Society for Microbiology.)

Objective: To compare HIV prevalence and HIV acquisition risk behaviors between pregnant women residents and migrants., Design: A cross-sectional study of pregnant women of unknown HIV status seeking care at Tijuana General Hospital, Mexico., Methods: Pregnant women attending the labor and delivery unit or the prenatal clinic had a rapid HIV test drawn, with positive results confirmed by Western blot. Migrants were defined as women who had resided in Tijuana for less than 5 years., Results: Between 2007 and 2008, a total of 3331 pregnant women consented to participate. The HIV seroprevalence did not differ between Tijuana residents (18 of 2502, 0.72%) and migrants (3 of 829, 0.36%, P = .32). In multivariate regression analyses, HIV acquisition risk behaviors included methamphetamine use (adjusted odds ratio [OR]: 6.03, 95% confidence interval [CI]: 2.3-15.8, P < .001) and first presentation at labor (adjusted OR: 5.0, 95% CI: 1.6-15.3, P = .005), adjusted for migrant status, age, and history of sexually transmitted infections., Conclusion: The overall HIV seroprevalence was 0.63% and did not differ between Tijuana residents and migrants., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2014.)

Objective: To assess the pharmacokinetics (PK), safety and efficacy of dolutegravir plus optimized background regimen in HIV-infected treatment-experienced adolescents., Methods: Children older than 12 to younger than 18 years received dolutegravir weight-based fixed doses at approximately 1.0 mg/kg once daily in a phase I/II multicenter open label 48-week study. Intensive PK evaluation was done at steady state after dolutegravir was added to a failing regimen or started at the end of a treatment interruption. Safety and HIV RNA and CD4 cell count assessments were performed through week 48., Results: Twenty-three adolescents were enrolled and 22 (96%) completed the 48-week study visit. Median age and weight were 15 years and 52 kg, respectively. Median [interquartile range (IQR)] baseline CD4+ cell count was 466 cells/μL (297, 771). Median (IQR) baseline HIV-1 RNA log10 was 4.3 log10 copies/mL (3.9, 4.6). Dolutegravir geometric mean of the area under the plasma concentration-time curve from time of administration to 24 hours after dosing (AUC0-24) and 24 hour postdose concentration (C24) were 46.0 μg hours/mL and 0.90 μg/mL, respectively, which were within the study targets based on adult PK ranges. Virologic success with an HIV RNA <400 copies/mL was achieved in 74% [95% confidence interval (CI): 52-90%] at week 48. Additionally, 61% (95% CI: 39-80%) had an HIV RNA <50 copies/mL at week 48. Median (IQR) gain in CD4 cell count at week 48 was 84 cells/μL (-81, 238). Dolutegravir was well tolerated, with no grade 4 adverse events, serious adverse events or discontinuations because of serious adverse events., Conclusions: Dolutegravir achieved target PK exposures in adolescents. Dolutegravir was safe and well tolerated, providing good virologic efficacy through week 48.

Resistance to antiretroviral drugs is an increasingly prevalent challenge affecting both the adult and pediatric HIV-infected populations. Though data on the safety, pharmacokinetics, and efficacy of newer antiretroviral agents in children typically lags behind adult data, newer agents are becoming available for use in HIV-infected children who are failing to respond to or are experiencing toxicities with traditional antiretroviral regimens. Integrase strand transfer inhibitors are one such new class of antiretrovirals. Raltegravir has been US Food and Drug Administration (FDA) approved for use in patients over the age of 4 weeks. Elvitegravir is a second member of this class, and has the potential for use in children but does not yet have a Pediatric FDA indication. Dolutegravir, a second-generation integrase inhibitor, is approved for those older than 12 years. This review summarizes the use of integrase inhibitors in children and adolescents, and highlights the results of recent clinical trials.

The objective of this study was to identify determinants of human immunodeficiency virus (HIV) knowledge regarding mother-to-child transmission (MTCT) among pregnant women at Tijuana General Hospital, Baja California, Mexico. Between March and November 2003, patients from the prenatal care (n = 1294) and labor and delivery (L&D) units (n = 495) participated in a cross-sectional study to measure HIV knowledge. Less than one-third (30%) knew that HIV could be transmitted to a child during delivery, and 36% knew that HIV could be transmitted by breast-feeding. Only 27% knew that an MTCT could be prevented. Prenatal patients were more likely to know that MTCT was preventable (prenatal: 31% versus L&D 25%; P = .02). Logistic regression indicated that prenatal patients (odds ratio = 1.49, confidence interval 1.07-2.07) were more likely to know that HIV could be transmitted through breast-feeding. Overall, both groups had poor knowledge regarding MTCT of HIV., (© The Author(s) 2014.)

The clinical utility of genotypic drug resistance testing (DRT) in HIV-infected children on antiretroviral therapy (ART) is not well understood. HIV-infected patients aged <19 years undergoing DRT for virological failure were retrospectively enrolled. Indications for DRT and changes in HIV RNA load were recorded. Between January 2000 and December 2006, 57 patients had DRT. The most common indication for DRT was poor ART adherence (57.7% of patients). ART was changed in 50.9% of patients after DRT. Poor adherence was cited by clinicians for not changing ART significantly more often than any other reason (47.3%, P < 0.001). After DRT, significant improvement in HIV RNA load occurred independent of ART changes, though patients whose ART was modified were more likely to become undetectable (31.5% versus 7.0%, P < 0.001). Poor adherence was a significant factor for ordering DRT and for not changing ART in HIV-infected children.

The objectives of this study were to evaluate the performance of parallel rapid HIV testing and the presence of HIV-associated risk factors in pregnant women with unknown HIV status in Baja California, Mexico. Pregnant women attending the delivery unit or the prenatal clinic at Tijuana General Hospital had blood drawn for parallel rapid HIV testing with Determine™ HIV-1/2 and Uni-Gold™ Recombigen(®) HIV. The parallel rapid HIV test performance was compared to the enzyme immunoassay (EIA) and western blot. From September 2007 to July 2008, 1,383 (94%) of 1,464 women in labor and 1,992 (96%) of 2,075 women in prenatal care were enrolled. The HIV seroprevalence among women screened during labor (19/1,383, 1.37%, 95% CI: 0.85-2.18%) was significantly higher compared to those seeking prenatal care (5/1,992, 0.25%, 95% CI: 0.09-0.62%; p<0.001). Of 25 pregnant women testing positive by parallel rapid HIV testing 24 had a positive confirmatory western blot and one (0.03%) was confirmed as false positive. Additionally, two (0.06%) women had parallel rapid HIV discordant testing results; both tested negative by western blot. All women who tested negative by rapid testing had negative results on pooled EIA antibody testing. The overall sensitivity, specificity, and positive and negative predictive values of parallel rapid HIV testing were 100%, 99.9%, 96%, and 100%, respectively. These findings document a very high acceptance rate and an excellent performance of the parallel rapid HIV testing strategy during pregnancy.

This study characterizes temporal trends in HIV disease progression among perinatally infected children at a clinic in Baja California, Mexico. A total of 73 children were followed, 52% were categorized under US Centers for Disease Control and Prevention (CDC) classification group C with a mean age of 2.3 years (SD ± 3.16) at HIV diagnosis. For the years 1998 to 2001, 2002 to 2003, 2004 to 2005, and 2006 to 2007, highly active antiretroviral therapy (HAART) use increased to 60%, 75%, 83%, and 94% (P < .001) as did mean CD4 percentage of 23.4%, 23.2%, 26.9%, and 29.0%, respectively (P = .009), while HIV plasma RNA log(10) decreased significantly (4.49, 4.23, 4.00, and 3.79, respectively; P = .019). Overall mortality was 31% (23 of 73), with pneumonia being the most common cause of death (43% of all deaths) followed by tuberculosis (22%). Mortality rates declined from 30.4% to 25%, 8.9%, and 9.3% (p = 0.035) for the years 1998 to 2001, 2002 to 2003, 2004 to 2005, and 2006 to 2007, respectively. Kaplan-Meier survival analysis showed that median survival was 11.2 years; 1-, 2-, and 5-year survival was 87%, 83%, and 67%, respectively. These findings document a high but improving trend in morbidity and mortality of children perinatally infected with HIV in Tijuana, Baja California, Mexico.

This study evaluated an obstetrical program using rapid HIV testing for the prevention of mother-to-child HIV transmission (MTCT) in Baja California, Mexico. Between 2003 and 2005, 45 women in labor and 17 prenatal care women were HIV infected. Among labor patients, 14 (31%) delivered by cesarean section compared with 17 (100%) prenatal care patients (P < .001). Intravenous maternal zidovudine (ZDV) and infant oral ZDV were more frequently administered in prenatal care compared to labor patients: 94% versus 33% (P < .001) and 100% versus 79% (P < .001), respectively. All prenatal care women received combination therapy. All 10 HIV-infected infants were in the labor group, resulting in a MTCT rate of 23% (95% confidence interval [CI] 9.5-34.8) compared to 0% (95% CI 0-1.8; P < .001) among the prenatal care group. Five (50%) of the HIV-infected infants had an AIDS diagnosis and 2 (20%) died within 18 months of birth. Women diagnosed during labor had a high HIV MTCT and poor postnatal outcome.

Etravirine is an oral diarylpyrimidine compound, a second-generation human immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse transcriptase inhibitor (NNRTI) with expanded antiviral activity against NNRTI-resistant HIV-1, to be used in combination therapy for treatment-experienced patients. Compared with first-generation NNRTIs, etravirine has a high genetic barrier to resistance, and is better tolerated without the neuropsychiatric and hepatic side effects of efavirenz and nevirapine, respectively. Its safety profile is comparable to placebo with the exception of rash, which has been mild and self-limited in the great majority of patients. In phase III clinical trials among treatment-experienced patients harboring NNRTI-resistant HIV-1, etravirine in combination with an optimized background regimen (OBR) that included ritonavir-boosted darunavir demonstrated superior antiviral activity than the control OBR. In addition, patients on the etravirine arm had fewer AIDS-defining conditions, hospitalizations, and lower mortality compared with the OBR control arm.

Objective: Estimate the 2006 HIV prevalence among adults aged 15-49 from the general population and at-risk subgroups in Tijuana, Mexico., Methods: Demographic data was obtained from the 2005 Mexican census and HIV prevalence data was obtained from reports in the literature. We developed a population-based HIV prevalence model for the overall population and stratified it by gender. Sensitivity analysis consisted of estimating standard errors in the weighted-average point prevalence and calculating partial derivatives of each parameter., Results: HIV prevalence among adults was 0.54% (N = 4347) (range 0.22-0.86% [N = 1750-6944]). This suggests that 0.85% (range 0.39-1.31%) of men and 0.22% (0.04-0.40%) of women could have been HIV-infected in 2006. Men who have sex with men (MSM), followed by female sex workers who are injection drug users (FSW-IDU), FSW-non IDU, female IDU, and male IDU were the most at risk groups of infected individuals., Conclusions: The number of HIV-infected adults among at-risk subgroups in Tijuana is significant, highlighting the need to design tailored prevention interventions that focus on the specific needs of certain groups. According to our model, as many as 1 in 116 adults could potentially be HIV-infected.

Objective: To describe the morbidity and mortality associated with tuberculosis (TB) in human immunodeficiency virus (HIV) infected children in Baja California, Mexico., Methods: Retrospective review of the medical records of all children with perinatally acquired HIV infection evaluated at Tijuana General Hospital with a diagnosis of TB between 1998 and 2007. The Stegen-Toledo (ST) clinical criteria for the diagnosis of TB were used., Results: A total of 73 HIV-infected children were followed during the study period. Thirteen (18%) children were diagnosed with TB; one was confirmed by culture to be positive. Among these children, the mean ages at HIV and TB diagnosis were respectively 3.6 and 5.3 years. The mean ST score was 8.1; 10/13 had a score of >or=7, or highly probable TB. There were a cumulative 29 hospital admissions prior to TB diagnosis; 24 of these were due to pneumonia. The mean duration of symptoms at TB diagnosis was 73 days. The most common symptoms were cough (92%) and anorexia (85%). Seven patients (54%) had disseminated TB and five (39%) died as a consequence of TB., Conclusions: We observed high morbidity, hospital utilization and high mortality associated with TB among HIV-infected children in Baja California.

The primary objective of this study was to measure atazanavir-ritonavir and tenofovir pharmacokinetics when the drugs were used in combination in young adults with human immunodeficiency virus (HIV). HIV-infected subjects > or =18 to <25 years old receiving (> or =28 days) 300/100 mg atazanavir-ritonavir plus 300 mg tenofovir disoproxil fumarate (TDF) plus one or more other nucleoside analogs underwent intensive 24-h pharmacokinetic studies following a light meal. Peripheral blood mononuclear cells were obtained at 1, 4, and 24 h postdose for quantification of intracellular tenofovir diphosphate (TFV-DP) concentrations. Twenty-two subjects were eligible for analyses. The geometric mean (95% confidence interval [CI]) atazanavir area under the concentration-time curve from 0 to 24 h (AUC(0-24)), maximum concentration of drug in serum (C(max)), concentration at 24 h postdose (C(24)), and total apparent oral clearance (CL/F) values were 35,971 ng x hr/ml (30,853 to 41,898), 3,504 ng/ml (2,978 to 4,105), 578 ng/ml (474 to 704), and 8.3 liter/hr (7.2 to 9.7), respectively. The geometric mean (95% CI) tenofovir AUC(0-24), C(max), C(24), and CL/F values were 2,762 ng.hr/ml (2,392 to 3,041), 254 ng/ml (221 to 292), 60 ng/ml (52 to 68), and 49.2 liter/hr (43.8 to 55.3), respectively. Body weight was significantly predictive of CL/F for all three drugs. For every 10-kg increase in weight, there was a 10%, 14.8%, and 6.8% increase in the atazanavir, ritonavir, and tenofovir CL/F, respectively (P < or = 0.01). Renal function was predictive of tenofovir CL/F. For every 10 ml/min increase in creatinine clearance, there was a 4.6% increase in tenofovir CL/F (P < 0.0001). The geometric mean (95% CI) TFV-DP concentrations at 1, 4, and 24 h postdose were 96.4 (71.5 to 130), 93.3 (68 to 130), and 92.7 (70 to 123) fmol/million cells. There was an association between renal function, tenofovir AUC, and tenofovir C(max) and intracellular TFV-DP concentrations, although none of these associations reached statistical significance. In these HIV-infected young adults treated with atazanavir-ritonavir plus TDF, the atazanavir AUC was similar to those of older adults treated with the combination. Based on data for healthy volunteers, a higher tenofovir AUC may have been expected, but was not seen in these subjects. This might be due to faster tenofovir CL/F because of higher creatinine clearance in this age group. Additional studies of the exposure-response relationships of this regimen in children, adolescents, and adults would advance our knowledge of its pharmacodynamic properties.

At Tijuana General Hospital, between March 2003 and June 2005, pregnant women and other adults, recently identified as HIV infected, antiretroviral naïve, were enrolled to examine the prevalence of primary HIV drug resistance. All subjects had the Calypte HIV-1 BED Incidence enzyme immunoassay test to identify recent infection. Genotypic analysis of HIV-1 protease and reverse transcriptase regions in plasma was performed. Forty-six subjects participated, eight (17%) men, 38 (83%) women. Ten (22%) subjects were classified as having recent HIV infection. HIV genotype was performed in 41 subjects. One subject (2.5%) had a major mutation in the reverse transcriptase region (K219Q) conferring zidovudine resistance, one had a minor mutation at V118I (2.5%) and two subjects (5%) had minor mutation (V179D) associated with non-nucleoside reverse transcriptase inhibitor resistance. There were no major protease inhibitor-associated mutations but minor mutations were common. The prevalence of primary HIV drug resistance in Baja California is low.

Objective: To evaluate the acceptance of counseling and rapid HIV testing and to determine the associated risk factors for HIV infection in pregnant women in Baja California, Mexico., Methods: Pregnant women attending Tijuana General Hospital who consented to participate in the study had blood drawn for a rapid HIV test (Determine HIV-1/2; Abbott Diagnostics, North Chicago, IL). A confirmatory enzyme immunoassay and Western blot were performed and demographic and risk factor data were obtained., Results: From March to November 2003, 1529 (92.5%) of 1653 women who sought prenatal care and 1068 (95.2%) of 1122 women in labor consented to participate. HIV seroprevalence was significantly higher among women screened during labor (12/1068, 1.12%) compared with those seeking prenatal care (5/1529, 0.33%). HIV-infected women were significantly more likely to use injection drugs (12% vs. 1%, P = 0.02), "other" drugs, including methamphetamine, marijuana, and cocaine (65% vs. 6%, P < 0.001), to have more sex partners (3.6 vs. 2.6, P = 0.0002), to not have received prenatal care (41% vs. 13%, P = 0.03), and to have a spouse/partner who used injection drugs (36% vs. 4%, P < 0.001) or "other" drugs (73% vs. 23%, P < 0.001). In multivariate regression analysis, use of methamphetamine (adjusted odds ratio, 17.8, 95% CI, 5.6-56) was independently associated with the risk of HIV infection., Conclusions: These findings indicate a wide acceptance of HIV counseling and testing and document a higher HIV seroprevalence among pregnant women delivering at Tijuana General Hospital than current established estimates in Mexico.

Background: The impact of highly active antiretroviral therapy (HAART) on human immunodeficiency virus type 1 (HIV-1) disease progression in perinatally infected children is not well documented. This study aims to identify the effect of evolving antiretroviral therapy on the immunologic and virologic status of and hospitalization and mortality rates among perinatally infected children., Methods: Children receiving outpatient care during 1994-2001 at 3 HIV clinics in southern California were observed longitudinally for CD4+ cell percentage, plasma HIV-1 RNA load, antiretroviral treatment, Pneumocystis jiroveci pneumonia (PCP) prophylaxis, and rate of hospital admissions., Results: A total of 129 children were observed during the study period; 51% were girls, and 40.3% were Hispanic, 29.5% were African American, and 27.1% were white. The mean CD4+ cell percentage increased from 22.5% in 1994 to 31.2% in 2001 (P<.01), and the mean plasma HIV-1 RNA load decreased from 4.53 log10 copies/mL in 1996 to 3.27 log10 copies/mL in 2001 (P<.001). The use of HAART increased from 0% in 1994 to 93% in 2001 (P<.01), whereas the use of PCP prophylaxis decreased from 55% to 16% during this time (P<.001). The hospitalization rate decreased from 6.49 to 0.60 admissions per 100 person-years during 1994-2001 (P<.001). Acquired immunodeficiency syndrome-associated hospital admission rates decreased from 15.6% in 1994 to 0% in 2001 (P<.0001). Similarly, the admission rate for patients with Centers for Disease Control and Prevention category B decreased from 29.7% in 1994 to 5.9% in 2001 (P<.0001). Logistic regression analysis showed that CD4+ cell percentage and viral load were independently associated with risk of hospitalization. Survival was significantly longer for those who received HAART., Conclusions: HIV-1-associated mortality and hospitalization rates decreased significantly between 1994 and 2001 in perinatally infected children. This correlated with an increase in CD4+ cell percentage and a decrease in HIV-1 RNA load concurrently with the expanded use of HAART.

A child with perinatally acquired AIDS and profound immunodeficiency was treated with zidovudine, lamivudine and indinavir and had excellent immunologic and virologic response. His subsequent clinical course was complicated by multisystem sarcoidosis characterized by granulomatous hepatitis, nephritis, duodenitis and a CD4+ lymphocytic alveolitis as part of the immune reconstitution syndrome.

Objectives: Newer combination antiretroviral therapies used to treat human immunodeficiency virus (HIV)-infected individuals have resulted in dramatic delays in HIV progression, with reduction in mortality and morbidity. However, adherence to highly active antiretroviral therapy (HAART) may be problematic, particularly in HIV-infected children. Reasons for nonadherence include refusal, drug tolerability, and adverse reactions. We assess: 1) the potential benefits of gastrostomy tube (GT) for the improvement of adherence to HAART in HIV-infected children, and 2) the factors that may result in improved viral suppression after GT placement., Methods: The medical records of 17 pediatric HIV-infected patients, in whom GT was used to improve HAART adherence, were retrospectively reviewed for clinical and laboratory parameters. Each record was reviewed for the period of 1 year before and after GT insertion. The main outcome parameters were virologic (plasma HIV RNA polymerase chain reaction quantification) and immunologic (CD4 cell counts). Documentation of adherence to medications in medical records was also assessed during the study. Parental questionnaires were used to determine GT satisfaction and medication administration times. The Wilcoxon rank sum test was used to assess change in viral load (VL) and CD4 cell percentages., Results: GT was well-tolerated with minor complications, such as local site tenderness, reported by 4 patients (23%). Before GT insertion, only 6 patients (35%) were documented as being adherent, compared with all patients after GT insertion. Ten patients (58%) had >/=2 log(10) VL decline after GT insertion (median: 3.2 log(10)), compared with 7 patients (42%) who had /=2 log(10) VL decline, therapy was changed at the time of or soon after GT insertion (median:.8 months; range: 0-6 months), compared with 7 patients with <2 log(10) VL decline who had therapy changed before GT insertion (median: 3.2 months; range: 1-8 months). Parental questionnaires reported significantly shorter medication administration times after GT insertion, with 70% of patients taking >5 minutes before GT, compared with 0% after GT. Questionnaires indicated satisfaction with GT, with perceived benefits being reduced medication administration time and improved behavior surrounding taking medications., Conclusions: GT is well-tolerated in pediatric HIV-infected patients and should be considered for selected patients to overcome difficulties with medication administration and to improve adherence. For maximal virologic response, combination therapy should be changed at the time of GT insertion.

There is no consensus regarding the specific management of HIV-associated nephrotic syndrome. We report a child whose first manifestation of human immunodeficiency virus type 1 (HIV-1) infection was nephropathy and wasting syndrome associated with profound immunodeficiency. The patient had a dramatic clinical and immunologic response to triple antiretroviral therapy delivered through a gastrostomy tube, with complete resolution of nephrotic syndrome. A 51/2-year-old African-American girl presented with a 2-week history of cough, chest pain, vomiting, loose stools, abdominal distention, anorexia, and fever. In addition, she had recurrent oral thrush. Her weight and height were below the 5th percentile. She was chronically ill, appearing with oropharyngeal thrush and pitting edema in lower extremities. She had scattered rhonchi and decreased breath sounds on both lung bases. Her abdomen was distended and diffusely tender. A chest radiograph showed consolidation of the right upper and left lower lobes with bilateral pleural effusion. Admission laboratories were consistent with nephrotic syndrome. Streptococcus pneumoniae grew from the blood culture and the child responded well to treatment with intravenous ceftriaxone. She was found to be HIV-infected, her CD4(+) cell count was 3 cells/mcL and her plasma HIV-1 RNA was >750 000 copies/mL. A percutaneous gastrostomy tube was placed for supplemental nutrition. She was treated with stavudine, lamivudine, and nelfinavir via gastrostomy tube with good clinical response. Twenty-one months after instituting antiretroviral therapy, her weight and height had increased to the 50th and 10th percentile respectively, and she had complete resolution of her nephrotic syndrome. Her CD4(+) cell count increased to 1116 cells/mcL and her viral load has remained undetectable. HIV-1 associated nephrotic syndrome has been described in children with profound immunodeficiency. The course of untreated HIV-associated nephrotic syndrome is rapid progression to renal failure in up to 40% of the children. Regardless of the presence of renal insufficiency, if untreated, it is uniformly fatal. A modest improvement of HIV-1 associated nephrotic syndrome has been observed in patients treated with zidovudine. Steroid and cyclosporine treatment have resulted in improved renal function but long-term use of immunosuppressive therapy has raised concerns about safety. We have described, to our knowledge, the first child with HIV-associated nephrotic syndrome who had a remarkable clinical, immunologic, and virologic response to triple-drug combination therapy given by gastrostomy tube, with complete resolution of proteinuria and normalization of the serum albumin. She also had a striking improvement in weight, height, and quality-of-life. Whether the presence of a gastrostomy tube contributed to the excellent response because of improved compliance is unknown, but warrants systematic evaluation.

The records of 20 children with imported malaria admitted to Kings County Hospital between October 1987 and May 1995 were reviewed. All had a history of recent travel or immigration from a malaria endemic area (West-Africa [16], Central-America [three], and the Caribbean [one]). None of the 10 children with a travel history received appropriate malaria chemoprophylaxis. The most common symptoms and signs were daily fever, chills, and hepatomegaly. Diagnosis was delayed in seven children who were initially felt to have pharyngitis or viral syndrome. Common laboratory findings were anemia and thrombocytopenia. P. falciparum was identified in 70% of the patients. Other species were P. malariae and P. vivax. Complications occurred in six children, hyponatremia in five, seizures in three, and cerebral malaria in one patient. The high incidence of chloroquine-resistant malaria makes chemoprophylaxis difficult in children. The clinical presentation of malaria is nonspecific, and diagnostic delays occur, so a high index of suspicion is needed in children with a travel history.

Obturator internus muscle (OIM) abscess is an uncommon entity often mistaken for septic arthritis of the hip. We describe seven children with OIM abscess and review seven previously reported cases. The most common presenting symptoms were hip or thigh pain (14 patients), fever (13), and limp (13). The hip was flexed, abducted, and externally rotated in 11 patients. Magnetic resonance imaging and computed tomography (CT) were diagnostic for OIM abscess in the 14 patients. Associated abscesses were located in the obturator externus muscle (5 patients), psoas muscle (2), and iliac muscle (1). The etiologic agents were Staphylococcus aureus (8 patients), Streptococcus pyogenes (2), Neisseria gonorrhoeae (2), and Enterococcus faecalis (1). Three patients underwent CT-guided percutaneous drainage, and three had surgical drainage. Three patients had ischial osteomyelitis in addition to OIM abscess. The 11 children with uncomplicated OIM abscess were treated for a median of 28 days. All patients had an uneventful recovery.

Baseline and posttreatment human immunodeficiency virus type 1 (HIV-1) isolates from 38 symptomatic, zidovudine-experienced HIV-1-infected children enrolled in a prospective trial of zalcitabine (dideoxycytidine) monotherapy (Pediatric AIDS Clinical Trials Group 138) were studied for the presence of syncytium-inducing (SI) phenotype and zalcitabine resistance. Twenty of the isolates were SI and 18 were non-SI (NSI) at baseline. After >44 weeks of zalcitabine treatment, the SI and NSI phenotypes were maintained in 16 and 17 patients, respectively. One patient had an NSI-to-SI phenotypic switch, while SI-to-NSI reversion occurred in 4 children (20%). Isolates from 30 of these patients were analyzed by in vitro drug susceptibility assay: Mean IC50 values were 0.14 microM at baseline and 0.18 microM following zalcitabine treatment. Only 1 child (3%) developed zalcitabine resistance. Knowledge of the low incidence of zalcitabine resistance and the switch from SI to NSI phenotype in some children may prove useful when selecting antiretroviral drugs to be used in combination.