Michelle S. McConnell

Trends in antiretroviral therapy use and survival rates for a large cohort of HIV-infected children and adolescents in the United States, 1989-2001.

Background:In the United States, HIV-infected children and adolescents are aging and using antiretroviral (ARV) therapy for extended periods of time. Objective:To assess trends in ARV use and long-term survival in an observational cohort of HIV-infected children and adolescents in the United States. Methods:The Pediatric Spectrum of HIV Disease Study (PSD) is a prospective chart review of more than 2000 HIV-infected children and adolescents. Patients were included in the analysis from enrollment until last follow-up. Results:Triple-ARV therapy use (for 6 months or more) increased from 27% to 66% during 1997 to 2001 (P < 0.0001, χ2 for trend). The proportion of patients receiving 3 or more sequential triple-therapy regimens also increased from 4% to 17% during 1997 to 2001 (P < 0.0001, χ2 for trend), however, and the durability of triple-therapy regimens decreased from 13 to 7 months from the first to third regimen. Survival rates for the 1997 to 2001 birth cohorts were significantly better than for the 1989 to 1993 and 1994 to 1996 cohorts (P < 0.0001). Conclusions:Survival rates in the PSD cohort have increased in association with triple-ARV therapy use. With continued changes in ARV regimens, effective modifications in ARV therapy and the sustainability of gains in survival need to be determined.

Effectiveness of Non-nucleoside Reverse-Transcriptase Inhibitor-Based Antiretroviral Therapy in Women Previously Exposed to a Single Intrapartum Dose of Nevirapine: A Multi-country, Prospective Cohort Study

In a comparative cohort study, Jeffrey Stringer and colleagues investigate the risk of ART failure in women who received single-dose nevirapine for PMTCT, and assess the duration of increased risk.

National expansion of antiretroviral treatment in Thailand 2000-2007: program scale-up and patient outcomes.

Objective:Thailand began a national antiretroviral (ARV) treatment program in 2000, and all government and some private and university hospitals now provide treatment to eligible HIV-infected patients. We describe program scale-up and patient outcomes from 2000 to 2007. Methods:Data from 839 hospitals in all 76 provinces of Thailand were included in this analysis. Outcomes were assessed for patients initiating ARV treatment from January 2000 to December 2005. Follow-up data through March 2007 were included; lost to follow-up was defined as >3 months late for a follow-up visit. A Cox proportional hazard model was used to assess risk factors for death; the Kaplan-Meier method was used to estimate survival probabilities. Results:Outcome data are reported for 58,008 patients. Among these, 52.2% were male; at treatment initiation, the median age was 34 years, the median CD4 count was 41 cells per cubic millimeter, and 50.5% had AIDS. The initial regimen was nevirapine and 2 nonnucleoside reverse transcriptase inhibitors for 92.4% of patients; median follow-up time was 1.6 years (interquartile range = 0.8-2.4 years). Lost to follow-up occurred in 8.8% of patients. Overall 1-year survival was 0.89 (95% confidence interval = 0.88 to 0.89). Death was significantly associated with male sex, age >40 years, baseline CD4 count <100 cells per cubic millimeter, symptomatic HIV or AIDS, receipt of services at a district or community hospital, and treatment initiation before 2005. Conclusions:National ARV treatment programs can be scaled up rapidly with good patient outcomes. Treatment outcomes among patients in Thailand are comparable to those reported in smaller cohorts in other countries, and survival rates have improved since 2004.

Optimization of a Low Cost and Broadly Sensitive Genotyping Assay for HIV-1 Drug Resistance Surveillance and Monitoring in Resource-Limited Settings

Commercially available HIV-1 drug resistance (HIVDR) genotyping assays are expensive and have limitations in detecting non-B subtypes and circulating recombinant forms that are co-circulating in resource-limited settings (RLS). This study aimed to optimize a low cost and broadly sensitive in-house assay in detecting HIVDR mutations in the protease (PR) and reverse transcriptase (RT) regions of pol gene. The overall plasma genotyping sensitivity was 95.8% (N = 96). Compared to the original in-house assay and two commercially available genotyping systems, TRUGENE® and ViroSeq®, the optimized in-house assay showed a nucleotide sequence concordance of 99.3%, 99.6% and 99.1%, respectively. The optimized in-house assay was more sensitive in detecting mixture bases than the original in-house (N = 87, P<0.001) and TRUGENE® and ViroSeq® assays. When the optimized in-house assay was applied to genotype samples collected for HIVDR surveys (N = 230), all 72 (100%) plasma and 69 (95.8%) of the matched dried blood spots (DBS) in the Vietnam transmitted HIVDR survey were genotyped and nucleotide sequence concordance was 98.8%; Testing of treatment-experienced patient plasmas with viral load (VL) ≥ and <3 log10 copies/ml from the Nigeria and Malawi surveys yielded 100% (N = 46) and 78.6% (N = 14) genotyping rates, respectively. Furthermore, all 18 matched DBS stored at room temperature from the Nigeria survey were genotyped. Phylogenetic analysis of the 236 sequences revealed that 43.6% were CRF01_AE, 25.9% subtype C, 13.1% CRF02_AG, 5.1% subtype G, 4.2% subtype B, 2.5% subtype A, 2.1% each subtype F and unclassifiable, 0.4% each CRF06_CPX, CRF07_BC and CRF09_CPX. Conclusions The optimized in-house assay is broadly sensitive in genotyping HIV-1 group M viral strains and more sensitive than the original in-house, TRUGENE® and ViroSeq® in detecting mixed viral populations. The broad sensitivity and substantial reagent cost saving make this assay more accessible for RLS where HIVDR surveillance is recommended to minimize the development and transmission of HIVDR.

Reduction in mother-to-child transmission of HIV in Thailand, 2001-2003: Results from population-based surveillance in six provinces.

Background:In 2000, Thailand implemented a national program to prevent mother-to-child HIV transmission (PMTCT). Objective:To describe the effectiveness of the prevention of mother-to-child HIV transmission program in Thailand. Design and methods:A register of HIV-exposed children at birth was created with follow-up of infection status. The register included children born to HIV-infected women between 1 January 2001 and 31 December 2003 at 84 public health hospitals in six provinces of Thailand. The main outcome measure was HIV infection in children. Results:A total of 2200 children born to HIV-infected mothers were registered. Of these mother–infant pairs, 2105 (95.7%) received some antiretroviral prophylaxis, including 1358 (61.7%) who received the complete short-course zidovudine regimen during pregnancy and labor for the mother and after birth for the infant, with or without other antiretrovirals. HIV infection outcome was determined for 1667 (75.8%) children, of whom 158 [9.5%, 95% confidence interval (CI), 8.1–11.0%] were infected. Transmission risk was 6.8% (95% CI 5.2–8.9%) among 761 mother–infant pairs that received the complete zidovudine regimen alone, and 3.9% (95% CI, 2.2–6.6%) among 361 mother–infant pairs that received the complete zidovudine regimen combined with other antiretrovirals, usually nevirapine. The overall transmission risk from this cohort, including all antiretroviral prophylaxis combinations, is estimated to be 10.2%. Conclusions:The Thai national PMTCT program is effective in reducing mother-to-child transmission risk from the historical risk of 18.9–24.2%. The addition of nevirapine to short-course zidovudine beginning in 2004 may further improve program effectiveness in Thailand.

Nevirapine‐associated hepatotoxicity was not predicted by CD4 count ≥250 cells/μL among women in Zambia, Thailand and Kenya

Objective The aim of the study was to determine risk factors for developing severe hepatotoxicity (grade 3 or 4 hepatotoxicity) and rash‐associated hepatotoxicity (rash with ≥grade 2 hepatotoxicity) among women initiating nevirapine‐based antiretroviral therapy (ART).

Reduced Mother-to-Child Transmission of HIV Associated with Infant but not Maternal GB Virus C Infection

BACKGROUND Prolonged coinfection with GB virus C (GBV-C) has been associated with improved survival in human immunodeficiency virus (HIV)-infected adults. We investigated whether maternal or infant GBV-C infection was associated with mother-to-child transmission (MTCT) of HIV-1 infection. METHODS The study population included 1364 HIV-infected pregnant women enrolled in 3 studies of MTCT of HIV in Bangkok, Thailand (the studies were conducted from 1992-1994, 1996-1997, and 1999-2004, respectively). We tested plasma collected from pregnant women at delivery for GBV-C RNA, GBV-C antibody, and GBV-C viral genotype. If GBV-C RNA was detected in the maternal samples, the 4- or 6-month infant sample was tested for GBV-C RNA. The rates of MTCT of HIV among GBV-C-infected women and infants were compared with the rates among women and infants without GBV-C infection. RESULTS The prevalence of GBV-C RNA in maternal samples was 19%. Of 245 women who were GBV-C RNA positive, 101 (41%) transmitted GBV-C to their infants. Of 101 infants who were GBV-C RNA positive, 2 (2%) were infected with HIV, compared with 162 (13%) of 1232 infants who were GBV-C RNA negative (odds ratio [OR] adjusted for study, 0.13 [95% confidence interval {CI}, 0.03-0.54]). This association remained after adjustment for maternal HIV viral load, receipt of antiretroviral prophylaxis, CD4(+) count, and other covariates. MTCT of HIV was not associated with the presence of GBV-C RNA (adjusted OR [aOR], 0.94 [95% CI, 0.62-1.42]) or GBV-C antibody (aOR, 0.90 [95% CI, 0.54-1.50]) in maternal samples. CONCLUSIONS Reduced MTCT of HIV was significantly associated with infant acquisition of GBV-C but not with maternal GBV-C infection. The mechanism for this association remains unknown.

Prevalence of Cryptococcal Antigenemia and Cost-Effectiveness of a Cryptococcal Antigen Screening Program – Vietnam

Background An estimated 120,000 HIV-associated cryptococcal meningitis (CM) cases occur each year in South and Southeast Asia; early treatment may improve outcomes. The World Health Organization (WHO) recently recommended screening HIV-infected adults with CD4<100 cells/mm3 for serum cryptococcal antigen (CrAg), a marker of early cryptococcal infection, in areas of high CrAg prevalence. We evaluated CrAg prevalence and cost-effectiveness of this screening strategy in HIV-infected adults in northern and southern Vietnam. Methods Serum samples were collected and stored during 2009–2012 in Hanoi and Ho Chi Minh City, Vietnam, from HIV-infected, ART-naïve patients presenting to care in 12 clinics. All specimens from patients with CD4<100 cells/mm3 were tested using the CrAg lateral flow assay. We obtained cost estimates from laboratory staff, clinicians and hospital administrators in Vietnam, and evaluated cost-effectiveness using WHO guidelines. Results Sera from 226 patients [104 (46%) from North Vietnam and 122 (54%) from the South] with CD4<100 cells/mm3 were available for CrAg testing. Median CD4 count was 40 (range 0–99) cells/mm3. Nine (4%; 95% CI 2–7%) specimens were CrAg-positive. CrAg prevalence was higher in South Vietnam (6%; 95% CI 3–11%) than in North Vietnam (2%; 95% CI 0–6%) (p = 0.18). Cost per life-year gained under a screening scenario was

Nevirapine Resistance in Women and Infants after First versus Repeated Use of Single-Dose Nevirapine for Prevention of HIV-1 Vertical Transmission

190,

National program scale-up and patient outcomes in a pediatric antiretroviral treatment program, Thailand, 2000-2007.

137, and