Risk factors associated with 10% weight change in treatment-naïve and treatment-experienced people living with HIV initiating or switching to an NNRTI- or INSTI-based antiretroviral therapy in four large cohort studies

Background: Pooled analyses of randomised controlled trials have shown weight gain (WG) following initiation/switching of antiretroviral therapy (ART) in people living with HIV (PLWHIV) [1,2]. We explored risk factors associated with ≥10% WG/weight loss (WL) in PLWHIV after initiating/switching ART. Materials and methods: Weight data were analysed from treatment-experienced (TE) and treatment-naïve (TN) PLWHIV enrolled in four Gilead-sponsored, post-authorisation, observational HIV cohort studies (2010 to 2020) and who initiated/switched non-nucleoside reverse transcriptase inhibitor (NNRTI)– or integrase strand transfer inhibitor (INSTI)–based ART. Participants had weight data available at baseline and 10 to 15 months post-baseline. Adjusted odds ratios (ORs) for potential risk factors for ≥10% WG/WL at 12 months in participants were estimated using multivariable logistic regression. Results: Two thousand, six hundred and sixty-six participants were included. Median age: 38 (TN)/47 years (TE). Of TE participants, 914/1939 (47%) switched from emtricitabine (F)/tenofovir disoproxil fumarate (TDF) backbone to F/tenofovir alafenamide (TAF), and 162/1939 (8%) from abacavir (ABC)/lamivudine (3TC) to F/TAF. Two hundred and twenty-nine of 727 (31%) TN participants had ≥10% WG (Table 1). Risk factors for ≥10% WG were F/TAF backbone (vs F/TDF; p < 0.001), low baseline CD4 (vs higher; p = 0.010), and being underweight (vs normal; p= 0.024; Figure 1). Eight of 727 (1%) TN participants had ≥10% WL. No significant risk factors for ≥10% WL were identified. Four hundred and fifty-one of 1939 (23%) TE participants had ≥10% WG (Table 1). Risk factors for ≥10% WG were INSTI-based ART (vs NNRTI; p = 0.029), F/TAF backbone (vs F/TDF; p < 0.001), being female (vs male; p = 0.002), switching from F/TDF to F/TAF (vs no switch; p = 0.001), being underweight (vs normal; p < 0.001), and having comorbidities associated with obesity (vs not; p = 0.046). Forty of 1939 (2%) TE participants had ≥10% WL. Only comedications associated with WL were predictors for ≥10% WL (OR 2.73 [95% CI 1.02 to 7.31]; p = 0.046). Conclusions: After initiating ART, WG was associated with F/TAF backbone, low baseline CD4 count, and being underweight in TN participants. In TE participants, WG was associated with INSTI-based ART, F/TAF backbone, switching from F/TDF to F/TAF, being female, and being underweight at baseline. Findings are consistent with the documented WG suppressive effect of F/TDF [3-6]. These data cannot determine the contribution of F/TAF to WG beyond the absence of the F/TDF WG suppressive effect. References: 1. Sax PE, Erlandson KM, Lake JE, Mccomsey GA, Orkin C, Esser S, et al. Weight gain following initiation of antiretroviral therapy: risk factors in randomized comparative clinical trials. Clin Infect Dis. 2020;71:1379-89. 2. Erlandson KM, Carter CC, Melbourne K, Brown TT, Cohen C, Das M, et al. Weight change following antiretroviral therapy switch in people with viral suppression: pooled data from randomized clinical trials. Clin Infect Dis. 2021;73:1440-51. 3. Glidden DV, Mulligan K, McMahan V, Anderson PL, Guanira J, Chariyalertsak S, et al. Metabolic effects of preexposure prophylaxis with coformulated tenofovir disoproxil fumarate and emtricitabine. Clin Infect Dis. 2018;67:411-9. 4. Ogbuagu O, Ruane PJ, Podzamczer D, Salazar LC, Henry K, Asmuth DM, et al. Long-term safety and efficacy of emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV-1 pre-exposure prophylaxis: week 96 results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet HIV. 2021;8:e397-e407. 5. Landovitz RJ, Donnell D, Clement M, Hanscom B, Cottle L, Coelho L, et al. HPTN 083 final results: Pre-exposure prophylaxis containing long-acting injectable cabotegravir is safe and highly effective for cisgender men and transgender women who have sex with men. 23rd International AIDS Conference; 2020 Jul 6-10. Oral OAXLB01. 6. Shah S, Pilkington V, Hill A. Use of tenofovir disoproxil fumarate shows weight loss vs placebo: a meta-analysis of 7 clinical trials in 19,359 HIV-negative individuals. IDWeek 2021; 2021 Sep 29-Oct 3; virtual. Poster P882