Risk of Incident Diabetes Mellitus, Weight Gain, and Their Relationships With Integrase Inhibitor-Based Initial Antiretroviral Therapy Among Persons With Human Immunodeficiency Virus in the United States and Canada.

BACKGROUND: Integrase strand transfer inhibitor (INSTI)-based combination antiretroviral therapy (cART) is associated with greater weight gain among persons with human immunodeficiency virus (HIV), though metabolic consequences, such as diabetes mellitus (DM), are unclear. We examined the impact of initial cART regimen and weight on incident DM in a large North American HIV cohort (NA-ACCORD). METHODS: cART-naive adults (≥18 years) initiating INSTI-, protease inhibitor (PI)-, or nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens from January 2007 through December 2017 who had weight measured 12 (±6) months after treatment initiation contributed time until clinical DM, virologic failure, cART regimen switch, administrative close, death, or loss to follow-up. Multivariable Cox regression yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident DM by cART class. Mediation analyses, with 12-month weight as mediator, similarly adjusted for all covariates. RESULTS: Among 22 884 eligible individuals, 47% started NNRTI-, 30% PI-, and 23% INSTI-based cART with median follow-up of 3.0, 2.3, and 1.6 years, respectively. Overall, 722 (3%) developed DM. Persons starting INSTIs vs NNRTIs had incident DM risk (HR, 1.17 [95% CI, .92-1.48]), similar to PI vs NNRTI initiators (HR, 1.27 [95% CI, 1.07-1.51]). This effect was most pronounced for raltegravir (HR, 1.42 [95% CI, 1.06-1.91]) vs NNRTI initiators. The INSTI-DM association was attenuated (HR, 1.03 [95% CI, .71-1.49] vs NNRTIs) when accounting for 12-month weight. CONCLUSIONS: Initiating first cART regimens with INSTIs or PIs vs NNRTIs may confer greater risk of DM, likely mediated through weight gain.

Physical Activity Intensity is Associated with Symptom Distress in the CNICS Cohort.

Symptom distress remains a challenging aspect of living with HIV. Physical activity is a promising symptom management strategy, but its effect on symptom distress has not been examined in a large, longitudinal HIV-infected cohort. We hypothesized that higher physical activity intensity would be associated with reduced symptom distress. We included 5370 people living with HIV (PLHIV) who completed patient-reported assessments of symptom distress, physical activity, alcohol and substance use, and HIV medication adherence between 2005 and 2016. The most frequent and burdensome symptoms were fatigue (reported by 56%), insomnia (50%), pain (46%), sadness (45%), and anxiety (45%), with women experiencing more symptoms and more burdensome symptoms than men. After adjusting for age, sex, race, time, HIV medication adherence, alcohol and substance use, site, and HIV RNA, greater physical activity intensity was associated with lower symptom intensity. Although individual symptoms may be a barrier to physical activity (e.g. pain), the consistent association between symptoms with physical activity suggests that more intense physical activity could mitigate symptoms experienced by PLHIV.