Molecular Characterization of the Gene of Vertically Transmitted HIV-1 Strains in Children with Virological Failure.

HIV-1 gene sequences were analyzed from 77 HIV-1 positive children infected perinatally and exhibiting virological failure (VF). Viral subtyping, phylogenetic analysis, and genotypic drug resistance analysis were carried out on samples collected before start of anti retroviral treatment (ART) (baseline, BL), and at 12 months post-ART initiation (M12). Subtype C was found to be most predominant, seen in 75 of the 77 (97.4%) children. The level of pretreatment drug resistance (PDR) was 14% among these children. At BL, K103N (5), E138A/G (4), and M184V (3) were the most common mutations. At M12 the prevalence of any resistance-associated mutation (RAM) (acquired drug resistance/ADR) was 81.8% (63/77). Dual class resistance mutations were seen in 64% (49/77) of children. M184V/I, K103N/S, and Y181C were the most commonly occurring mutations, seen in 76%, 51%, and 36% children. RAMs to the second-generation non-nucleoside reverse transcriptase inhibitors (NNRTI), etravirine (ETR) and rilpivirine (RPV), were seen in 40.2% (31/77) and 48.05% (37/77) of the children, respectively. Our findings reveal similar prevalence rates of PDR and ADR in children with VF as reported in other studies. Occurrence of ETR and RPV resistance associated mutations (RAMs) is of concern and highlights the need for timely switch of regimens guided by genotypic resistance testing in perinatally infected children from India

Geographic and behavioral differences associated with sexually transmitted infection prevalence among Indian men who have sex with men in Chennai and Mumbai

BACKGROUND: India has one of the largest numbers of men who have sex with men (MSM) globally, however, geographic data on sexually transmitted infection (STI) prevalence and associations with sexual behavior are limited. METHODS: Six-hundred-eight MSM in Chennai and Mumbai screening in for a behavioral trial and assessed bacterial STI (syphilis, chlamydia, gonorrhea), HIV, and past-month self-reported condomless anal sex (CAS). RESULTS: Mumbai (37.8%) had a greater prevalence of any STIs than Chennai (27.6%) (est=1.37, 95% CI:1.09,1.73). This pattern also emerged for gonorrhea and chlamydia separately but not syphilis. Conversely, Mumbai had lower CAS (M=2.2) compared to Chennai (M=14.0) (est=−11.8, 95% CI:−14.6,−9.1). The interaction of city by CAS on any STI prevalence (PR=2.09, 95% CI:1.45,3.01, p<.0001) revealed that in Chennai, higher CAS was not associated with STI prevalence, but in Mumbai it was (PR=2.49, 95% CI:1.65,3.76, p<.0001). DISCUSSION: Higher bacterial STIs but lower CAS in Mumbai versus Chennai, and the significant interaction of CAS with city on STIs suggests that either differences in disease burden or differences by city with respect to self-reported assessment of CAS. Regardless, the high prevalence rates of untreated STI and condomless sex among MSM suggests the need for additional prevention intervention efforts for MSM in urban India

Host lipidome and tuberculosis treatment failure

INTRODUCTION: Host lipids play important roles in tuberculosis (TB) pathogenesis. Whether host lipids at TB treatment initiation (baseline) affect subsequent treatment outcomes has not been well characterised. We used unbiased lipidomics to study the prospective association of host lipids with TB treatment failure. METHODS: A case–control study (n=192), nested within a prospective cohort study, was used to investigate the association of baseline plasma lipids with TB treatment failure among adults with pulmonary TB. Cases (n=46) were defined as TB treatment failure, while controls (n=146) were those without failure. Complex lipids and inflammatory lipid mediators were measured using liquid chromatography mass spectrometry techniques. Adjusted least-square regression was used to assess differences in groups. In addition, machine learning identified lipids with highest area under the curve (AUC) to classify cases and controls. RESULTS: Baseline levels of 32 lipids differed between controls and those with treatment failure after false discovery rate adjustment. Treatment failure was associated with lower baseline levels of cholesteryl esters and oxylipin, and higher baseline levels of ceramides and triglycerides compared to controls. Two cholesteryl ester lipids combined in a unique classifier model provided an AUC of 0.79 (95% CI 0.65–0.93) in the test dataset for prediction of TB treatment failure. CONCLUSIONS: We identified lipids, some with known roles in TB pathogenesis, associated with TB treatment failure. In addition, a lipid signature with prognostic accuracy for TB treatment failure was identified. These lipids could be potential targets for risk-stratification, adjunct therapy and treatment monitoring

APOC3 Gene Polymorphism and Antiretroviral Therapy-Induced Dyslipidemia in HIV-Infected Children

Children exposed to antiretroviral therapy (ART) are at risk of developing metabolic complications. The association between gene polymorphisms and the development of dyslipidemia in children post ART initiation was studied. Children initiating first-line ART were followed for 2 years at the National Institute for Research in Tuberculosis (Chennai, India), and St. John's Medical College Hospital (Bangalore, India). Clinical examination and fasting serum lipid profiles were measured every 6 months. Participants were genotyped for the polymorphisms in the APOC3 gene (rs2854116; rs2854117, and rs5128). Changes in lipid levels from baseline to months 6, 12, and 24, and the difference between the various genotype variants were analyzed using a modified analysis of variance test. Study enrolled 393 ART-naive HIV-infected children (mean age: 7.6 ± 3 years, mean weight: 18 ± 6) of whom 289 (75%) were started on nevirapine (NVP)-based ART and the remaining 96 (25%) were started on efavirenz-based ART. Only children carrying the GG allele of rs5128 genotype showed a decrease in CD4% and serum triglycerides pre-ART. An increasing trend of total cholesterol, high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol were seen at 6 months in both EFZ and NVP groups, which subsequently stabilized by 12 months irrespective of genotype variants. Genotype variants of APOC3 (rs2854116 and rs2854117 polymorphism) did not show significant changes in serum lipid levels after 24 months of ART, whereas rs5128 polymorphism with “G” allele showed an association with HDL-c levels when on NVP-based ART. Our results suggest that ART plays a major role in normalizing lipid levels in HIV-infected children and APOC3 polymorphisms may not play a significant role in ART-induced dyslipidemia

Long-term virological outcome in children receiving first-line antiretroviral therapy

Abstract Background Studies relating to long-term virological outcomes among children on first-line antiretroviral therapy (ART) from low and middle-income countries are limited. Methods Perinatally HIV infected, ART-naive children, between 2 and 12 years of age, initiating NNRTI-based ART during 2010–2015, with at least 12 months of follow-up, were included in the analysis. CD4 cell counts and plasma HIV-1 RNA were measured every 24 weeks post-ART initiation. Immunologic failure was defined as a decrease in the CD4 count to pre-therapy levels or below and virologic failure as HIV-RNA of > 1000 copies/ml at 48 weeks after ART initiation. Genotypic resistance testing was performed for children with virologic failure. Logistic regression analysis was done to identify predictors of virologic failure. Results Three hundred and ninety-three ART-naïve children living with HIV [mean (SD) age: 7.6 (3) years; mean (SD) CD4%: 16% (8); median (IQR) HIV-RNA: 5.1 (3.5–5.7) log10 copies/ml] were enrolled into the study. At 48 weeks, significant improvement occurred in weight-for-age and height-for-age z-scores from baseline (all p  90% adherence to ART. At the time of virologic failure, multiple NNRTI-associated mutations were observed: 80%—K103N and Y181C being the major NNRTI mutations—observed. Sensitivity (95% CI) of immunologic failure to detect virologic failure was 7% (2–12), specificity 97% (92.4–98.9), PPV 44% (13.7–78.8) and NPV was 72% (65–77.9). There were no statistically significant predictors to detect children who will develop virologic failure on treatment. Conclusions Considerable immunological improvement is seen in children with ART initiation, but may not be an effective tool to monitor treatment response in the long-term. There is a lack of correlation between immunologic and virologic response while on ART, which may lead to a delay in identifying treatment failures. Periodic viral load monitoring is, therefore, a priority