Asian people with HIV gain weight after starting treatment at similar rate to other ethnic groups

Weight gain after starting integrase inhibitor-based antiretroviral treatment occurs to a similar extent in Asian adults with HIV compared to previously studied populations in North America and southern Africa, researchers from the TREAT Asia cohort report in HIV Medicine.

Clinical trials carried out in North America, Europe and South Africa have shown a consistent pattern of greater weight gain after starting treatment in people who receive integrase inhibitor-based treatment. For example, a pooled analysis of eight large clinical trials carried out between 2003 and 2015 found that although the average weight gain two years after starting treatment was 2kg, people taking integrase inhibitors gained 3.2 kg and people taking bictegravir or dolutegravir gained just over 4kg.

In South Africa, the ADVANCE study observed similar levels of weight gain after 96 weeks in people taking dolutegravir with the old formulation of tenofovir (TDF) and greater weight gain (just over 8kg in women and 5kg in men) when it was combined with tenofovir alafenamide (TAF).

None of these studies included substantial numbers of Asian participants so until now it has been unclear if similar patterns of weight gain are occurring in people with HIV in Asia. If there are ethnic differences in weight gain on integrase inhibitor-based treatment, these might be explained by baseline weight, by genetics, or by diet and other lifestyle factors that may vary between ethnic groups.

TREAT Asia researchers wanted to understand the prevalence of obesity and metabolic syndrome in people receiving antiretroviral treatment in Asia and to assess whether these conditions were more prevalent in people receiving integrase inhibitor-based treatment.

The TREAT Asia HIV Observational Database (TAHOD) covers 21 HIV treatment centres in 12 countries: Cambodia, China, Hong Kong, India, Indonesia, Japan, Malaysia, the Philippines, Singapore, South Korea, Taiwan, Thailand and Vietnam. People with HIV receiving treatment at these centres were eligible for inclusion in the analysis if they had baseline weight measurements and at least one measurement more than three months after starting treatment. The study excluded people with baseline obese body mass index (>27.5 kg/m²). The metabolic syndrome analysis included people with body mass and metabolic measurements at least three months after starting treatment. People with abnormal baseline blood pressure, HDL cholesterol, triglycerides or glucose at baseline were excluded.

A total of 4931 people with HIV were eligible for inclusion in the study, 4535 in the weight analysis and 3503 in the metabolic syndrome analysis. The study population was 66% male, the majority had started treatment with CD4 counts below 200 (64%) and the majority were either underweight (25%) or in the normal weight range (50%) before starting treatment. Most had started treatment with a non-nucleoside reverse transcriptase inhibitor-based regimen (91%) and only 58 people (1%) had received an integrase inhibitor.

After three years of antiretroviral treatment, study participants had gained a median of 3.7kg (3kg after two years). Men and people with lower baseline weight gained more weight. People taking an integrase inhibitor gained a median of 5.6kg after three years (5.2kg after two years) compared to 3.6kg in people taking an non-nucleoside reverse transcriptase inhibitor (p<0.05). In multivariable analysis greater weight gain was associated with a prior AIDS diagnosis, being underweight at baseline or integrase inhibitor treatment. Women and those who were overweight at baseline had lower weight gain.

Despite the fact that 74% started treatment with a thymidine analogue (zidovudine or stavudine), the time period during which people started treatment had only a modest effect on weight gain. Use of thymidine analogues was phased out after 2010 due to side-effects, especially fat loss (lipoatrophy), although the speed at which this happened depended on access to generic versions of tenofovir. People who started treatment between 2013 and 2019 gained an additional 0.8kg compared to people who started treatment between 2003 and 2007 (p<0.009).

During follow-up, 8.4% of participants developed metabolic syndrome, defined as central obesity and at least two of the following: elevated triglycerides or treatment for dyslipidaemia, depressed HDL cholesterol or treatment for dyslipidaemia, elevated blood pressure or treatment for hypertension, or diagnosis of type 2 diabetes or treatment with oral hyperglycaemic drugs.

"Asian men gained more weight than women, whereas in other studies women consistently gained more weight than men."

In a multivariable regression analysis, development of metabolic syndrome was associated with being overweight at baseline, stavudine exposure, higher viral load, lower CD4 count and AIDS-defining illness during follow-up. There was no association between other antiretrovirals and metabolic syndrome. Metabolic syndrome was also associated with greater weight gain over three years of antiretroviral treatment. Metabolic syndrome was not associated with an increased risk of death.

The study investigators note that the weight gain observed in the TREAT Asia cohort was comparable to the changes in weight observed in the pooled analysis of clinical trials. They also point out that their findings on greater weight gain in people with lower CD4 counts or a prior AIDS diagnosis reflect the findings of previous studies in other regions. However, they also highlight a difference with previous studies: Asian men gained more weight than women, whereas in other studies women consistently gained more weight than men. These findings suggest that “the sex differences in weight gain are not similar across different races among PLWH populations.”