Behavioral Health and Adult Milestones in Young Adults With Perinatal HIV Infection or Exposure

BACKGROUND: Young adults living with perinatally acquired HIV infection (PHIVYAs) are at risk for poor biomedical and behavioral health outcomes. Few studies offer a comprehensive overview of the functioning of this population in young adulthood and the role of HIV. METHODS: Data come from the Child and Adolescent Self-Awareness and Health Study, a longitudinal behavioral health cohort study of PHIVYAs and perinatally HIV-exposed but uninfected young adults (PHEUYAs) who are compared on psychiatric and neurocognitive functioning, sexual and substance use behaviors, health and reproductive outcomes, and young adult milestones. RESULTS: Overall, 27% of participants met criteria for a psychiatric disorder, including mood (11%), anxiety (22%), and substance use (28%), with no HIV status differences. PHIVYAs performed worse on 2 neurocognitive tests. There were no HIV status differences in condomless sex (41%) or pregnancies (41% women; 38% men). Both groups exhibited similar adult milestones: 67% graduated high school or an equivalent, 19% were in college, and 42% were employed. However, 38% were neither in school or working, 12% reported incarceration, and 16% were ever homeless. Among PHIVYAs, 36% were viremic (\u3e200 copies per mL), and 15% were severely immunocompromised (CD4(+) cell count \u3c100 cells per mm(3)). CONCLUSIONS: Many PHIVYAs achieve adult milestones related to school, employment, sexual relationships, and starting families. However, they and PHEUYAs have high rates of psychiatric and substance use disorders and behavioral risks, which can jeopardize long-term health and adult functioning, particularly in the context of HIV. These findings underscore an urgent need to escalate interventions

First-line antiretroviral therapy with a protease inhibitor versus non-nucleoside reverse transcriptase inhibitor and switch at higher versus low viral load in HIV-infected children: An open-label, randomised phase 2/3 trial

Background: Children with HIV will be on antiretroviral therapy (ART) longer than adults, and therefore the durability of first-line ART and timing of switch to second-line are key questions. We assess the long-term outcome of protease inhibitor and non-nucleoside reverse transcriptase inhibitor (NNRTI) first-line ART and viral load switch criteria in children. Methods: In a randomised open-label factorial trial, we compared effectiveness of two nucleoside reverse transcriptase inhibitors (NRTIs) plus a protease inhibitor versus two NRTIs plus an NNRTI and of switch to second-line ART at a viral load of 1000 copies per mL versus 30 000 copies per mL in previously untreated children infected with HIV from Europe and North and South America. Random assignment was by computer-generated sequentially numbered lists stratified by age, region, and by exposure to perinatal ART. Primary outcome was change in viral load between baseline and 4 years. Analysis was by intention to treat, which we defined as all patients that started treatment. This study is registered with ISRCTN, number ISRCTN73318385. Findings: Between Sept 25, 2002, and Sept 7, 2005, 266 children (median age 6\ub75 years; IQR 2\ub78-12\ub79) were randomly assigned treatment regimens: 66 to receive protease inhibitor and switch to second-line at 1000 copies per mL (PI-low), 65 protease inhibitor and switch at 30 000 copies per mL (PI-higher), 68 NNRTI and switch at 1000 copies per mL (NNRTI-low), and 67 NNRTI and switch at 30 000 copies per mL (NNRTI-higher). Median follow-up was 5\ub70 years (IQR 4\ub72-6\ub70) and 188 (71%) children were on first-line ART at trial end. At 4 years, mean reductions in viral load were -3\ub716 log10copies per mL for protease inhibitors versus -3\ub731 log10copies per mL for NNRTIs (difference -0\ub715 log10copies per mL, 95% CI -0\ub741 to 0\ub711; p=0\ub726), and -3\ub726 log10copies per mL for switching at the low versus -3\ub720 log10copies per mL for switching at the higher threshold (difference 0\ub706 log10copies per mL, 95% CI -0\ub720 to 0\ub732; p=0\ub756). Protease inhibitor resistance was uncommon and there was no increase in NRTI resistance in the PI-higher compared with the PI-low group. NNRTI resistance was selected early, and about 10% more children accumulated NRTI mutations in the NNRTI-higher than the NNRTI-low group. Nine children had new CDC stage-C events and 60 had grade 3/4 adverse events; both were balanced across randomised groups. Interpretation: Good long-term outcomes were achieved with all treatments strategies. Delayed switching of protease-inhibitor-based ART might be reasonable where future drug options are limited, because the risk of selecting for NRTI and protease-inhibitor resistance is low. Funding: Paediatric European Network for Treatment of AIDS (PENTA) and Pediatric AIDS Clinical Trials Group (PACTG/IMPAACT). \ua9 2011 Elsevier Ltd