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Weight gain after antiretroviral therapy initiation and subsequent risk of metabolic and cardiovascular disease
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sept 12 2023
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Sara H. Bares1, Xingye Wu2, Katherine Tassiopoulos3, Jordan E. Lake4, Susan L. Koletar5,
Robert Kalayjian6, Kristine M. Erlandson7, For the A5322 Study Team
Randomized Trials)[10] began enrolling participants previously enrolled into ACTG randomized trials. A5001 followed participants every 4 months through 2013. In 2013, A5001 follow-up ended and participants 40 years of age or older from treatment-naive parent trials were offered enrollment into A5322 (the HIV Infection, Aging, Immune Function Long-Term Observational Study [HAILO]), which followed participants for 8 years, initially every 6 months (through 2019) and then annually. This analysis included A5001 and A5322 participants who had participated in trials including any of the following antiretrovirals: tenofovir disoproxil fumarate, emtricitabine, lamivudine, abacavir, efavirenz, atazanavir, darunavir, and raltegravir (A5142, A5202 and A5257).
In summary, ours is the first analysis of long-term cardiometabolic complications following short-term weight changes that occur after ART initiation that also includes analysis to evaluate the impact of sex and race/ethnicity on these outcomes. These data confirm the negative impact of short-term weight gain as evidenced by significant increases in the risks of incident DM, metabolic syndrome, and CV events as well as the positive impact of short-term weight loss on incident metabolic syndrome. The data also highlight important sex differences in the impact of weight gain on incident DM which illustrates the importance of investigating mechanisms other than weight gain when studying the excess risk of DM in women with HIV. Additional research is needed to determine whether weight control interventions at the time of ART initiation may help to minimize the risk of subsequent cardiometabolic disease.
Association between weight change at week 48 and incident CV events
Thirty-two individuals with prevalent CV events and one with a CV event that occurred within the first 48 weeks after ART initiation were excluded. Twenty-eight incident CV events occurred after week 48. After adjusting for age, history of DM, hypertension or dyslipidemia at baseline, family history of cardiovascular disease, smoking status, baseline CD4 count and HIV-1 RNA, weight change was not associated with incident CV events. Association between waist circumference change at week 48 and metabolic and clinical outcomes Similar associations were observed for an increase in waist circumference of >7cm versus ā¤3cm and all metabolic and clinical outcomes.
Results
Participants (nā=ā2624) were primarily male (81%) and non-White (60%). Mean weight gain from 0-48 weeks was 3.6 kg (SD 7.3); 130 participants developed DM; 360 metabolic syndrome; 424 any cardiometabolic event; 28 any cardiovascular event, over 480 weeks of follow-up. In adjusted models, total cholesterol increased by 0.63 mg/dL (95% CI 0.38, 089) and LDL by 0.39 mg/dL (0.19, 0.59) per 1 kg increase in weight from weeks 0-48. Participants who experienced >10% weight gain (vs -5% to 5%) had an increased risk of DM (HR 2.01, 95% CI [1.30, 3.08]), metabolic syndrome (HR 2.24 [1.55, 2.62]), and cardiometabolic outcomes (HR 1.54, 95% CI [1.22, 1.95]). Participants who lost more than 5% of their baseline weight had a lower risk of incident metabolic syndrome (HR 0.67 [0.42, 1,07]). Trends for WC were similar.
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