gs-7340 and Obesity

Integrase inhibitors, including dolutegravir (DTG), are associated with weight gain and obesity, especially when combined with tenofovir alafenamide (TAF). Obesity increases the risk of adverse pregnancy outcomes (APOs). This study aimed to predict the risk of APOs caused by treatment-associated obesity, using a hypothetical sample based on the ADVANCE trial.. Risk prediction.. Firstly, a meta-analysis was performed to determine the relative risk (RR) for APOs in women with obese (≥30) versus normal prepregnancy BMIs (18.5-24.9). For the hypothetical sample, 3000 nonpregnant women with normal BMIs at Week 0 of treatment were evenly allocated across the following treatment arms: TAF/FTC+DTG, TDF/FTC+DTG, TDF/FTC/EFV. The treatment-associated obesity rates from ADVANCE were used to calculate the number of women with obese and normal BMIs expected at Week 96 in our sample. This was combined with the APO RRs to predict the number of women at risk of APOs, in each treatment arm, assuming they conceived at Week 96.. At Week 96, the percentage of women predicted to be obese was 14.1% with TAF/FTC+DTG, 7.9% with TDF/FTC+DTG and 1.5% with TDF/FTC/EFV. The RR in women with obese versus normal BMIs was significantly higher for most APOs. Therefore, the number of women at risk of APOs was higher with TAF/FTC+DTG than TDF/FTC+DTG and TDF/FTC/EFV. For example, 11/1000 additional gestational hypertension cases were predicted with TAF/FTC+DTG, 6/1000 with TDF/FTC+DTG and 1/1000 with TDF/FTC/EFV.. Treatment-associated obesity increased the APO risk in women. This risk is likely to increase, as preliminary data from ADVANCE demonstrates ongoing weight gain beyond Week 96.

Topics: Alanine; Alkynes; Anti-HIV Agents; Benzoxazines; Cyclopropanes; Emtricitabine; Female; Heterocyclic Compounds, 3-Ring; HIV Infections; Humans; Obesity; Oxazines; Piperazines; Pregnancy; Pregnancy Outcome; Pyridones; Tenofovir

Topics: Adult; Alanine; Anti-HIV Agents; HIV Infections; Humans; Lipids; Obesity; Tenofovir; Weight Gain

Tenofovir-based antiretroviral therapy (ART) has become first-line in all major HIV treatment guidelines. Compared with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) has a favorable renal and bone safety profile, but concerns about metabolic complications remain.. To assess weight changes, the development of overweight/obesity, and changes in lipid levels 18 months after replacing TDF with TAF.. Cohort study.. 5 university hospitals, affiliated hospitals, and private physicians in Switzerland.. 4375 adults living with HIV who received TDF-containing ART for 6 months or longer.. Changes in weight and lipid levels were assessed using mixed-effect models. Differences in proportions of newly overweight/obese participants were calculated using 2-proportions. 4375 individuals were included, with follow-up between 1 January 2016 and 31 July 2019. Median age was 50 years (interquartile range, 43 to 56 years), 25.9% were female, and 51.7% had a normal body mass index (BMI); 3484 (79.6%) switched to TAF and 891 (20.4%) continued TDF. After 18 months, switching to TAF was associated with an adjusted mean weight increase of 1.7 kg (95% CI, 1.5 to 2.0 kg), compared with 0.7 kg (CI, 0.4 to 1.0 kg) with the continued use of TDF (between-group difference, 1.1 kg [CI, 0.7 to 1.4 kg]). Among individuals with a normal BMI, 13.8% who switched to TAF became overweight/obese, compared with 8.4% of those continuing TDF (difference, 5.4 percentage points [CI, 2.1 to 8.8 percentage points]). Switching to TAF led to increases in adjusted mean total cholesterol (0.25 mmol/L [9.5 mg/dL]), high-density lipoprotein cholesterol (0.05 mmol/L [1.9 mg/dL]), low-density lipoprotein cholesterol (0.12 mmol/L [4.7 mg/dL]), and triglyceride (0.18 mmol/L [16.1 mg/dL]) levels after 18 months.. Short follow-up, small subgroup analyses, and potential residual confounding.. Replacing TDF with TAF is associated with adverse metabolic changes, including weight increase, development of obesity, and worsening serum lipid levels.. Swiss National Science Foundation.

Topics: Adult; Alanine; Anti-HIV Agents; Blood Glucose; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Female; HIV Infections; Humans; Lipids; Male; Middle Aged; Obesity; Sensitivity and Specificity; Tenofovir; Triglycerides; Weight Gain