The safety, toxicity, and pharmacokinetics of intrapartum and early newborn nevirapine were evaluated in 17 human immunodeficiency virus type 1-infected women in labor and their newborns. No adverse effects of nevirapine were noted in any study mothers or infants. Following maternal dosing with 200 mg during labor, concentrations exceeding 100 ng/mL (10 times the in vitro IC50) were achieved in the newborns. Nevirapine elimination was prolonged in both mothers and infants, with median half-lives ranging from 36.8 to 65.7 h. Administration of 200 mg orally to the mothers in labor and of a single 2-mg/kg oral dose to the infants at 48-72 h after birth maintained serum concentrations in the infants > 100 ng/mL through 7 days of life.

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.

The AACTG DNA bank will be an important resource for genomic discovery relevant to HIV therapy.

Abstract 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.

Objective: We assessed differences in mitochondrial function between youth living with perinatal HIV (YPHIV) and youth perinatally HIV-exposed but uninfected (YPHEU).Design: Cross-sectional analysis. Methods:We measured lactate and pyruvate values, as well as mitochondrial Complex I and Complex IV activity in peripheral blood mononuclear cells. Logistic or linear regression models were fit, as appropriate, to assess the association between PHIV status and each mitochondrial parameter, adjusted for confounders. We introduced interaction terms to assess effect modification of PHIV status on the relationship between anthropometric factors and each mitochondrial parameter. Among YPHIV, similar regression models were fit to assess the relationship between HIV-associated factors and each mitochondrial outcome.Results: A total of 243 YPHIV and 118 YPHEU were compared. On average, YPHIV had higher lactate/pyruvate ratio (b: 7.511, 95% confidence interval [95% CI]: 0.402, 14.620) and Complex IV activity (b: 0.037, 95% CI: 0.002, 0.072) compared to YPHEU, adjusted for confounders. Among YPHIV, body mass index Z score (BMIZ) and Complex I activity were inversely associated, whereas, among YPHEU, there was a positive association (b for interaction: À0.048, P ¼ 0.003). Among YPHIV, current (b: À0.789, 95% CI: À1.174, À0.404) and nadir CD4 þ % (b: À0.605, 95% CI: À1.086, À0.125) were inversely associated with lactate/pyruvate ratio; higher current (4.491, 95% CI: 0.754, 8.229) and peak (7.978, 95% CI: 1.499, 14.457) HIV RNA levels were positively associated with lactate/pyruvate ratio in adjusted models.Conclusions: Mitochondrial function and substrate utilization appear perturbed in YPHIV compared to YPHEU. Increasing immunosuppression and viremia are associated with mitochondrial dysfunction among YPHIV.

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A linking procedure establishes a “bridge” between the scores from different patient-reported outcome (PRO) instruments that measure similar constructs. After developing a linking relationship however, it is critical to evaluate whether this relationship can be generalized to different groups. Our study aims to validate a published crosswalk for score conversion between the Brief Symptom Inventory Depression subscale and the Patient-Reported Outcomes Measurement Information System Depression 8a using an independent sample. Data were from a sample of young men who have sex with men (MSM), which differs in terms of participant age, race, and ethnicity from the sample used to develop the existing crosswalk. The validity of the newly derived crosswalk was evaluated in terms of the correlation, mean difference and standard deviation between the observed and the linked scores. The two crosswalks were further compared to evaluate if the difference was within an acceptable range. More than half of the item parameters obtained from the two samples were found to overlap in their confidence intervals. Differences between each pair of scores in the two crosswalks was within three T-score points, well within the range of each crosswalk score’s standard error. This study concludes that an existing crosswalk is replicable on a sample that differs from that used for crosswalk development, but future research should continue to examine the generalizability of the linked parameters and evaluate the reproducibility of this crosswalk to other populations.

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