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Background Patterns of antiretroviral therapy (ART) use and immunologic correlates vary globally, and contemporary trends are not well described. Methods The REPRIEVE trial (Randomized Trial to Prevent Vascular Events in HIV) enrolled persons with human immunodeficiency virus (HIV) who were aged 40–75 years, receiving ART, and had low-to-moderate cardiovascular disease risk. ART use was summarized within Global Burden of Disease (GBD) super-regions, with adjusted linear and logistic regression analyses examining associations with immune parameters and key demographics. Results A total of 7770 participants were enrolled, with a median age of 50 years (interquartile range, 45–55 years); 31% were female, 43% were black or African American, 15% were Asian, 56% had a body mass index >25 (calculated as weight in kilograms divided by height in meters squared), and 49% were current or former smokers. The median CD4 T-cell count was 620/µL (interquartile range, 447–826/ µ L), and the median duration of prior ART use, 9.5 years (5.3–14.8) years. The most common ART regimens were nucleoside/nucleotide reverse-transcriptase inhibitor (NRTI) plus nonnucleoside reverse-transcriptase inhibitor (43%), NRTI plus integrase strand transfer inhibitor (25%), and NRTI plus protease inhibitor (19%). Entry ART varied by GBD region, with shifts during the trial enrollment period. In adjusted analyses, entry CD4 cell count and CD4/CD8 ratio were associated with GBD region, sex, entry regimen, duration of ART, and nadir CD4 cell count; CD4 and CD8 cell counts were also associated with body mass index and smoking status. Conclusions There were substantial variations in ART use by geographic region and over time, likely reflecting the local availability of specific medications, changes in treatment guidelines and provider/patient preferences. The analyses of CD4 cell counts and CD4/CD8 ratios may provide valuable insights regarding immune correlates and outcomes in people living with HIV. Clinical Trials Registration NCT02344290.

An understanding of the relationships among allelic variability and clinical outcomes will be critical if HIV-infected patients are to benefit from the explosion in knowledge in human genomics. Human DNA banks must allow future analyses while addressing confidentiality, ethical, and regulatory issues.A multidisciplinary group of clinical investigators, ethicists, data managers, regulatory specialists, and community representatives developed Adult AIDS Clinical Trials Group (AACTG) Protocol A5128. Participants in past or present AACTG clinical trials may contribute DNA. Extraction from whole blood is performed at a central laboratory, where participants' unique identifiers are replaced by randomly assigned identifiers prior to DNA storage. To identify genotype-phenotype relationships, genetic assay results can be temporarily linked to clinical trials data.Institutional review boards in 21 states and Puerto Rico have approved Protocol A5128, and accrual is ongoing. Of the first 4,247 enrollees, 82% are male, 56% are white, 26% are African American, and 15% are Hispanic. Because participants may participate in multiple AACTG protocols, these represent 11,424 cases in 324 different AACTG studies and substudies, with at least 100 participants from 24 different studies. Studies exploring specific genotype-phenotype relationships are underway.The AACTG DNA bank will be an important resource for genomic discovery relevant to HIV therapy.

The safety, toxicity and pharmacokinetics of nevirapine were studied in HIV-infected pregnant women beginning chronic therapy late in the third trimester and in their infants. Initial dose pharmacokinetic profiles in the pregnant women were similar to those seen in nonpregnant adults. Serum nevirapine concentrations fell below the 100-ng/ml target concentration by Day 7 of life in four infants, suggesting that nevirapine elimination is accelerated in these infants compared with newborns whose mothers receive only a single intrapartum nevirapine dose.