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.ConclusionsThe 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.

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.

BackgroundAn 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.MethodsSerum 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.ResultsSera 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 $190, $137, and $119 at CrAg prevalences of 2%, 4% and 6%, respectively.ConclusionCrAg prevalence was higher in southern compared with northern Vietnam; however, CrAg screening would be considered cost-effective by WHO criteria in both regions. Public health officials in Vietnam should consider adding cryptococcal screening to existing national guidelines for HIV/AIDS care.

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.

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.

Vietnam has a concentrated HIV epidemic, with the highest HIV prevalence being observed among people who inject drugs (PWID). Based on its experience scaling-up robust HIV interventions, Vietnam aims to further strengthen its response by harnessing the preventive benefits of antiretroviral therapy (ART). Mathematical modelling suggests that prioritizing key populations for earlier access to ART, combined with other prevention interventions, may have significant impact on the epidemic, cost-effectively reducing new HIV infections and deaths. Pilot studies are being conducted to assess feasibility and acceptability of expansion of HIV testing and counselling (HTC) and early ART among key populations and to demonstrate innovative service delivery models to address challenges in uptake of services across the care cascade. Earlier access of key populations to combination prevention interventions, combined with sustained political commitment and supportive environment for key populations, are essential for maximum impact of ART on the HIV epidemic in Vietnam.

ObjectiveThe 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). MethodsThe Non-Nucleoside Reverse Transcriptase Inhibitor Response Study was a prospective cohort study carried out in Zambia, Thailand and Kenya. Between May 2005 and January 2007, we enrolled antiretroviral-naïve HIV-infected women initiating nevirapine-based ART. At enrolment and at weeks 2, 4, 8, 16 and 24, participants had serum alanine transferase (ALT) and aspartate transaminase (AST) measured and were evaluated clinically for hepatitis and rash. ResultsNevirapine-based ART was initiated in 820 women and baseline ALT or AST results were abnormal ( ! grade 1) in 113 (14%) women. After initiating nevirapine-based ART, severe hepatotoxicity occurred in 41 (5%) women and rash-associated hepatotoxicity occurred in 27 (3%) women. In a multivariate logistic regression model, severe hepatotoxicity and rash-associated hepatotoxicity were both associated with baseline abnormal ( ! grade 1) ALT or AST results, but not with a baseline CD4 cell count ! 250 cells/mL. Three participants (0.4%) died with symptoms suggestive of fatal hepatotoxicity; all three women had baseline CD4 count o100 cells/mL and were receiving anti-tuberculosis therapy. ConclusionAmong women taking nevirapine-based ART, severe hepatotoxicity and rash-associated hepatotoxicity were predicted by abnormal baseline ALT or AST results, but not by a CD4 count ! 250 cells/mL. In resource-limited settings where transaminase testing is available, testing should focus on early time-points and on women with abnormal baseline ALT or AST results.

Single dose (SD) nevirapine (NVP) significantly reduces HIV mother-to-child transmission. We analyzed NVP resistance after SD NVP in 57 previously SD NVP-naїve women, 34 SD NVP-experienced women, and 17 HIV-infected infants. The proportion of women with resistance, the types of mutations detected, and the frequency and level of K103N were similar in the two groups of women at 6 weeks and 6 months post-partum. NVP resistance was detected in a similar proportion of infants born to SD NVP-naїve versus SD NVP-experienced women. Repeated use of SD NVP to prevent HIV transmission does not appear to influence NVP resistance.