Weight gain after switching to integrase inhibitor treatment is small in Dutch and Swiss cohorts

Black people and women most likely to experience substantial weight gain after switch

People with suppressed viral load who switched to an integrase inhibitor-based regimen experienced only small gains in weight and do not appear to gain more weight than HIV-negative people or people who continued taking other regimens, two large cohort studies presented at the 17th European AIDS Conference (EACS 2019) reported.

However, the Swiss HIV Cohort reported that people of African origin gained more weight after switching to dolutegravir, as did women, while a Dutch cohort study found that 24% of people who switched to an integrase inhibitor gained at least 5% of body weight. Substantial weight gain after switching was more likely in black women, although the number of black women in the cohort was small.

A recently published meta-analysis of eight large clinical trials found that weight gain after starting antiretroviral treatment was most strongly associated with a low CD4 count before starting treatment. The authors of that study suggested that more evidence from studies of switching treatment was needed to investigate immunological and antiretroviral predictors of weight gain. However, white men tend to be over-represented in switching studies.

Glossary

integrase inhibitors (INI, INSTI)

A class of antiretroviral drugs. Integrase strand transfer inhibitors (INSTIs) block integrase (see ‘integrase’). Blocking integrase prevents HIV from replicating.

integrase

HIV enzyme that the virus uses to insert its genetic material into a cell that it has infected.

observational study

A study design in which patients receive routine clinical care and researchers record the outcome. Observational studies can provide useful information but are considered less reliable than experimental studies such as randomised controlled trials. Some examples of observational studies are cohort studies and case-control studies.

matched

In a case-control study, a process to make the cases and the controls comparable with respect to extraneous factors. For example, each case is matched individually with a control subject on variables such as age, sex and HIV status. 

body mass index (BMI)

Body mass index, or BMI, is a measure of body size. It combines a person's weight with their height. The BMI gives an idea of whether a person has the correct weight for their height. Many BMI calculators can be found on the internet.

Two observational cohort studies of weight changes after switching treatment were presented at the conference. Both studies looked at the effects of switching to an integrase inhibitor-based regimen. (Other weight gain studies from the conference are reported herehere and here.)

AGEhIV Cohort, the Netherlands

AGEhIV is a large observational cohort that monitors the long-term health of people over the age of 45 on antiretroviral treatment in the Netherlands in comparison to a control group of HIV-negative people.

To examine the impact of integrase inhibitors on body weight, the cohort investigators designed a prospective observational study in which changes in body weight were monitored in people who switched to an integrase inhibitor-containing regimen. Each person was matched with two people who remained on non-integrase inhibitor treatment and two HIV-negative people. In each case, they were matched according to age, gender, ethnicity and body mass index.

The investigators also simulated a switch point for the controls, by identifying the point during pre-switch follow-up where the control participant most closely resembled the switch participant in characteristics including weight. They then used the time to switching treatment to define a simulated switch time in the control participants and monitored weight before and after 'switch' for the control participants.

"Looking at averages in switch studies may be less useful than looking at risk factors for clinically relevant weight gain of greater than 5kg."

The HIV cohort consisted of 598 people and the HIV-negative cohort of 550 people. One hundred and nineteen people switched to an integrase inhibitor-containing regimen (53% dolutegravir; 35% elvitegravir; 13% raltegravir).

The switch group was 89% white and 87% male, had been on antiretroviral treatment for a median of 12 years, had a median age of 55 years and a median body mass index of 24. As the two control groups were matched, proportions were similar in each group.

Body weight was measured twice a year, before and after switching. Throughout the follow-up period there was no significant difference in body weight changes between people who switched to an integrase inhibitor-containing regimen and matched HIV-positive and HIV-negative controls. The mean annual weight gain after switching to an integrase inhibitor was 0.17kg a year.

However, 24% of people who switched to an integrase inhibitor gained at least 5% in body weight compared with 13% of the HIV-positive control group (p = 0.012) and 12% of the HIV-negative control group (p = 0.004). Weight gain of 10% or more after switching to an integrase inhibitor occurred more frequently in black women than in other demographic groups, although the number of black women in the study cohort was small.

Swiss HIV Cohort

The Swiss HIV Cohort Study is a large observational cohort of people living with HIV receiving treatment at HIV clinics in Switzerland. Weight is measured at six-monthly clinic visits in all cohort members. Investigators analysed weight changes in people who had been virally suppressed for at least 18 months before switching to a dolutegravir-containing regimen, and who had at least 18 months of follow-up after switching.

In this cohort, 2186 people switched to dolutegravir and were eligible for analysis. (Women who were pregnant at the time of switching were excluded.) The switch population was predominantly male (75%) and white (81%), had been on antiretroviral therapy for a median of 11 years and had a median body mass index of 24 at time of switching.

In the 18 months preceding the switch, participants gained a median of 0.47kg (95% confidence interval 0.34-0.61). In the 18 months after switching, they gained a median of 0.72kg (95% CI 0.58-0.86), a significant difference (p < 0.029).

Whereas women showed no difference in the rate of weight gain after switching, men gained significantly more weight (p = 0.009), although the amount gained (+0.81kg) remained modest.

Ethnicity did not affect average weight gain, but when the researchers calculated the risk of gaining more than 5% in body weight after switching, they found that women, black people and current smokers had approximately 50% greater likelihood of substantial weight gain. People who were obese at the time of switching were less likely to have substantial weight gain.

Conclusion

The findings of both studies suggest that looking at averages or medians in switch studies may be less useful than looking at risk factors for clinically relevant weight gain of greater than 5kg, especially in cohorts that are predominantly white and male.

References

Mugglin C et al. Changes in weight after switching to dolutegravir containing antiretroviral therapy in the Swiss HIV cohort study. 17th European AIDS Conference, Basel, abstract PS3/5, 2019.

Verboeket S et al. Switching to an integrase inhibitor containing antiretroviral regimen is not associated with above-average weight gain in middle-aged people living with HIV on long-term suppressive antiretroviral therapy, the AGEhIV cohort study. 17th European AIDS Conference, Basel, abstract PS3/6, 2019.