72. Massive Weight Gain in People with HIV (PWH) Starting Initial Antiretroviral Therapy (ART): Risk Factors and Predictive Ability of Early Weight Gain

Abstract Background Using a clinic cohort of ART naïve PWH, we sought to understand factors associated with massive weight gain as well as to assess if early weight gain could help predict massive weight gain at two years. Methods This was a retrospective cohort study of PWH from a large, urban clinic initiating first ART from January 2005 through March 2019, who had 21 – 27 months follow-up without ART changes, and were suppressed (HIV-RNA < 200 cps/ml) during that time. We defined massive weight gain as the top 20% of weight gainers at two years measured by percent (%) gain compared to baseline. Using bivariate and multivariate logistic regression (including factors in bivariate analysis with p< 0.20), we assessed the association of demographics, ART regimen, baseline CD4 count, HIV viral load, and body mass index (BMI) with weight gain at 2 years. We also assessed early weight gain (between 4 and 12 wks) and its association with massive weight gain at two years. Results Of 266 PWH included (table1), the median age was 36 years (IQR 29 - 45), 9% were women, 14% black, and 43% Latino. Overall, median % weight gain at 2 years was 4% (-1.1 – 11.6) In bivariate analyses, baseline factors significantly associated with massive weight gain included lower CD4 count, higher viral load, and lower baseline BMI. In multivariate analysis the odds of having massive weight gain were higher with lower CD4 count, adjusted odds ratio (aOR) 0.8 (95% CI 0.6 – 0.9) per 100 cells/ul increase and higher viral load, aOR 2.6 (95% CI 1.4 – 4.6) per 1 log increase. Early weights were available for 217 individuals at a median of 56 days (IQR 44 – 63) after ART initiation. Early weight gain correlated with % weight gain at 2 years (R=0.58). Individuals with ≤ 3% early weight gain represented 66% of the population and had a 10% risk (14 of 144) of having massive weight gain at 2 years. In contrast, 43 individuals had > 5% early weight gain and their risk of massive weight gain at 2 years was 56% (24 of 43). Conclusion In this real-world dataset, drug class or specific NRTI use was not associated with massive weight gain which was primarily dependent on baseline CD4 count and HIV viral load. There was a moderate correlation between early weight gain and massive weight gain at 2 years which can help with patient counseling and interventions aimed at slowing weight gain in this population. Disclosures All Authors: No reported disclosures

Conclusion. Multimorbidity and polypharmacy are common in PLWH and have been increasing in prevalence over the past 5 years. Study findings highlight the importance of an individualized approach to care for a diverse PLWH population, in order to minimize drugdrug interactions and adverse events and thereby improve patient outcomes.

Massive Weight Gain in People with HIV (PWH) Starting Initial Antiretroviral Therapy (ART): Risk Factors and Predictive Ability of Early Weight Gain
Tanit Phupitakphol, MD 1 ; Dean McEwen, n/a 2 ; Kellie Hawkins, MD 3 ; Edward Gardner, MD 3 ; 1 University of Colorado, Denver, CO; 2 Denver Public Health, Denver, Colorado; 3 Denver Health and Hospital Authority, Denver, Colorado

Session: O-15. HIV Co-infections and Co-morbidities
Background. Using a clinic cohort of ART naïve PWH, we sought to understand factors associated with massive weight gain as well as to assess if early weight gain could help predict massive weight gain at two years.
Methods. This was a retrospective cohort study of PWH from a large, urban clinic initiating first ART from January 2005 through March 2019, who had 21 -27 months follow-up without ART changes, and were suppressed (HIV-RNA < 200 cps/ml) during that time. We defined massive weight gain as the top 20% of weight gainers at two years measured by percent (%) gain compared to baseline. Using bivariate and multivariate logistic regression (including factors in bivariate analysis with p< 0.20), we assessed the association of demographics, ART regimen, baseline CD4 count, HIV viral load, and body mass index (BMI) with weight gain at 2 years. We also assessed early weight gain (between 4 and 12 wks) and its association with massive weight gain at two years.
Results. Of 266 PWH included (table1), the median age was 36 years (IQR 29 -45), 9% were women, 14% black, and 43% Latino. Overall, median % weight gain at 2 years was 4% (-1.1 -11.6) In bivariate analyses, baseline factors significantly associated with massive weight gain included lower CD4 count, higher viral load, and lower baseline BMI. In multivariate analysis the odds of having massive weight gain were higher with lower CD4 count, adjusted odds ratio (aOR) 0.8 (95% CI 0.6 -0.9) per 100 cells/ul increase and higher viral load, aOR 2.6 (95% CI 1.4 -4.6) per 1 log increase. Early weights were available for 217 individuals at a median of 56 days (IQR 44 -63) after ART initiation. Early weight gain correlated with % weight gain at 2 years (R=0.58). Individuals with ≤ 3% early weight gain represented 66% of the population and had a 10% risk (14 of 144) of having massive weight gain at 2 years. In contrast, 43 individuals had > 5% early weight gain and their risk of massive weight gain at 2 years was 56% (24 of 43).

Conclusion.
In this real-world dataset, drug class or specific NRTI use was not associated with massive weight gain which was primarily dependent on baseline CD4 count and HIV viral load. There was a moderate correlation between early weight gain and massive weight gain at 2 years which can help with patient counseling and interventions aimed at slowing weight gain in this population.
Disclosures. Background. Lenacapavir (LEN) is a first-in-class HIV-1 capsid (CA) inhibitor in clinical development for treatment and prevention of HIV-1 infection. CALIBRATE is an ongoing, phase 2 clinical study evaluating subcutaneous (SC) or oral LEN, in combination with other antiretrovirals, in treatment-naïve people with HIV-1. High rates of virologic success (HIV-1 RNA < 50 copies/mL) were achieved with LEN-based regimens by FDA Snapshot analysis at Week 28. Here, we present interim resistance analyses through Week 28.

Figure. CALIBRATE Study Design
Results. 182 participants were randomized and dosed in TG-A to D (n=52, 53, 52, 25). Most participants had subtype B HIV-1 (92.9%). Sequence analysis of baseline samples found 65% of amino acid residues were conserved with < 1% variation across CA overall, and 55% of residues were fully conserved. No mutations were detected at 6 positions in CA associated with reduced susceptibility to LEN in vitro; residues were fully conserved at 5 positions (L56, M66, Q67, K70, N74), and < 2% variation was observed at 1 position (T107). Three participants met the criteria for resistance analysis: 2 participants resuppressed to < 50 copies/mL while continuing treatment. One participant on SC LEN + F/TAF developed emergent resistance to LEN (Q67H+K70R) and emtricitabine (M184M/I), followed by resuppression after starting dolutegravir, zidovudine + lamivudine, tenofovir disoproxil fumarate.
Conclusion. Emergent resistance to LEN was uncommon in treatment-naïve participants receiving SC or oral LEN (0.6%, 1/157). These interim resistance findings support the ongoing evaluation of LEN for treatment and prevention of HIV.
Disclosures Background. The APR is prospective exposure-registration cohort study, monitoring for early warning signals of major teratogenic effects of antiretrovirals (ARV) used during pregnancy. This analysis aimed to assess maternal demographics, pregnancy and neonatal outcomes including birth defects among infants with periconception and prenatal exposure to DTG using APR data.
Methods. Descriptive analysis with frequency tabulation of pregnancy and neonatal outcomes is reported. Periconception is defined as any exposure within two weeks prior to or through 28 days after conception.
Conclusion. APR data do not demonstrate an increased risk of overall birth defects with DTG use above the population expected rate of defects (2.72 to 4.17 per 100 live births from Metropolitan Atlanta Congenital Defects Program [MACDP] and Texas Birth Defects Registry [TBDR] respectively). The number of periconception exposure outcomes is not yet sufficient to evaluate potential association of DTG with NTD. The Registry continues to closely monitor birth defects, including NTDs in pregnancies exposed to DTG and other integrase inhibitors.