HIV disease is characterized by body composition changes which have been clinically identified by wasting syndrome in the pre-ART era, lipodystrophy in the early-ART era and overweight in the late-ART era. Recent studies have described an association between INSTI use and body weight increase.
The aim of this study was to assess weight gain and its associations with relevant health outcomes in body composition changes in PLWH switching to INSTI-based regimens in comparison to INSTI-naïve patients. Comparison between dual (2DR) and triple (3DR) drug regimens was described in this context.
We retrospectively analysed anthropometric and HIV variables, and comorbidities in ART-experienced PLWH from 2007 to 2019. Inclusion criteria were as follows: ART-experienced PLWH that were INSTI-naïve at the start of the observational period before the switch to the current regimen. At the moment of switch, patients were divided in two groups: patients who remained INSTI naïve and patients who switched to an INSTI regimen. The groups were matched for sex, age, baseline BMI and duration of the switch. Patients were then subdivided into 4 mutually exclusive groups according to classes and regimens: INSTI-sparing-3DR, INSTI-sparing-2DR, INSTI-3DR, INSTI-2DR. Weight gain was defined as an annualized predicted increase of 7% in BMI. Predictors of weight gain and body composition changes were analysed in multivariable regression model including baseline and follow up demographic, anthropometric, HIV related and comorbidities values. Loess curves were used to assess the relationship between weight gain and different ART regimens over time.
A total of 1158 PLWH (68.7% males) were included. Patients who switched to INSTI were evaluated at the baseline and after a follow up of 4 years (SD = 2.23). In this time frame, high statistically significant differences were found in the following measures: age, BMI, waist circumference (WC), fat free mass index (FFMI), appendicular skeletal muscle index (ASMI) and leg fat % (p<0.001). Mixed lipodystrophy, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were not statistically significant. A higher prevalence of multimorbidity and chronic kidney disease is observed. Never-INSTI group (N=513 at follow-up) showed statistically significant increase in age, BMI, WC, FFMI, ASMI, leg fat %, sarcopenia, VAT and SAT, multimorbidity (MM), hypertension, dyslipidemia and polypharmacy. The inter group comparison demonstrated an increase of leg fat %, sarcopenia and lipodystrophy in never-INSTI group, while INSTI-group demonstrated lower levels of CD4/CD8 ratio, current CD4 and a higher prevalence of MM. Higher prevalence of weight gain was observed in group who switched to INSTI (68.9% vs. 31.2%). It was observed that PLWH in the lowest category of BMI got more weight when compared to the groups with higher BMI. In a multivariate logistic model, independent predictor of weight gain was switch to INSTI (OR 2.57, 1.42-4.81), while the lower lumbar BMD (OR=0.04, 0.01-0.79) was negatively associated with weight gain. Lipodystrophy, ASMI and WC did not show any association. The use of 2DR and 3DR, INSTI and never-INSTI did not predict weight gain over time.
INSTI-based switch (equally in 2DR or 3DR) in PLWH did not necessarily involve changes in body composition. Weight gain may be related to an improvement in the underlying patient conditions, which was in most cases more underweight than those who did not use the same antiretroviral treatment. The impact of weight gain with relevant health outcomes in PLWH should be more investigated, particularly in the light of the fact that patients switching to INSTI-based regimens are often subjects with a high burden of comorbidities and immunological scars.