People with low CD4 counts and advanced HIV (AIDS) were far more likely to experience substantial weight gain after starting treatment than people who started treatment with CD4 counts above 350, a large French study has found. Those with advanced HIV gained on average just under 10kg, compared to just under 3kg in the latter group.
Greater weight gain in people with advanced HIV was associated with taking the integrase inhibitors dolutegravir or raltegravir. Tenofovir alafenamide was associated with greater weight gain than tenofovir disoproxil or abacavir. The French researchers say that the choice of treatment for people with advanced HIV should consider the risk of weight gain as well as the impact of treatment on viral load and CD4 count.
Current treatment guidelines in Europe and North America recommend that the first antiretroviral combination for people with HIV should contain an integrase inhibitor. This class of drug has been shown to reduce high viral load and improve CD4 counts more effectively than other agents.
But integrase inhibitors have been associated with substantial weight gain, which may increase the long-term risk of heart disease, diabetes and some cancers.
Studies of risk factors for weight gain after starting HIV treatment have consistently shown that a low CD4 count, or a high viral load, raises the risk of weight gain. Weight gain after starting treatment could be a ‘return to health’ effect in people with advanced HIV, as weight loss can be a consequence of living with untreated HIV. If HIV is suppressed, body weight tends to increase to a level that is normal for the age, gender and social setting of the person with HIV.
What has been unclear is how the ‘return to health’ effect observed in numerous studies is affected by the choice of antiretroviral agents, and how much weight gain differs between people who start treatment with higher or lower CD4 counts.
The French Hospital Database on HIV follows people with HIV receiving care at more than 180 hospitals in France. In this analysis, researchers looked at weight gain and the factors associated with it in 12,773 people with HIV who started treatment for the first time between 2012 and 2018. People starting treatment were included in the study if their weight was measured in the six months before starting treatment and they were followed for at least a year after starting treatment and had a weight measurement.
The researchers compared weight changes after starting treatment in two groups: ‘early presenters’ and ‘advanced HIV’.
- Early presenters: the 5,794 participants who began treatment with a CD4 count above 350 and a viral load below 100,000, or during the first few months of infection.
- Advanced HIV: the 3,106 participants who began treatment with a CD4 count below 200 or an AIDS diagnosis. Many in this group were severely immunosupressed: the median CD4 count was 105.
The groups of early presenters and people with advanced HIV differed in several ways. Early presenters were more often gay and bisexual men (57%) while people with advanced HIV were more often heterosexual (61%) and born in sub-Saharan Africa (36%). A higher proportion of early presenters were either in the overweight or obese body mass categories (33%) than in the advanced HIV group (25%) while a larger proportion of those with advanced HIV were underweight (12% vs 5%).
Early presenters were less likely to start treatment with a protease inhibitor-based regimen (30% vs 56%) and more likely to start treatment with a rilpivirine-based regimen (29% vs 5%) or an integrase inhibitor (35% vs 11%). There was no substantial difference in the use of efavirenz or nucleoside/nucleotide (NRTI) backbone between the two groups. Approximately three-quarters in each group received tenofovir disoproxil fumarate (TDF). No one in this study took bictegravir because it was not available until 2019.
"Although weight gain may be a ‘return to health’ effect, it might also be a symptom of long-term effects of uncontrolled HIV replication on fat tissue."
Substantial weight gain after 30 months of treatment was much more common among people with advanced HIV than early presenters. Almost two-thirds (63%) of those with advanced HIV experienced weight gain of at least 10% compared to 20% of early presenters. In people with advanced HIV, the risk of gaining at least 10% of bodyweight was almost twice as high in people taking raltegravir (hazard ratio 2.19), dolutegravir (HR 2.24) or darunavir (HR 1.96) compared to people taking rilpivirine, and in people with viral load above 500,000 (HR 2.03) compared to those with viral load below 30,000. Having had an AIDS-defining illness also doubled the risk of 10% weight gain (HR 2.05). Taking tenofovir alafenamide (TAF) raised the risk of at least 10% weight gain by approximately 50% (HR 1.52) compared to taking TDF.
An increase in body mass index of at least 5kg/m2 is associated with an increased risk of several common cancers and an increased risk of death in people who are already overweight. Almost one in four (24%) people with advanced HIV gained at least 5kg/m2 in body weight and the risk of gaining this amount of weight was the same for people who were underweight or in the obese weight category. This extent of weight gain was associated with treatment with raltegravir, dolutegravir or TAF.
Substantial weight gain was much less common among early presenters and risk factors were somewhat different. Whereas gender had only a small impact on weight gain among people with advanced HIV, female early presenters aged 50 and over had a 62% higher risk of 10% weight gain compared to men under 50. Dolutegravir, darunavir and atazanavir were associated with a 30-50% increase in the risk of 10% weight gain compared to rilpivirine.
After 30 months of follow-up, early presenters had gained an average of 2.8kg. Weight gain ranged from +1.7kg in people taking efavirenz to +3.5kg in people taking dolutegravir. In early presenters, the greatest weight gain occurred in the first year of treatment and wight gain after this point was modest.
People with advanced HIV gained an average of 9.7kg. Although the greatest weight gain occurred in the first year on treatment, weight continued to rise up to 30 months after starting treatment. Average weight gain ranged from +8.4kg in people taking elvitegravir to +10.8kg in people taking dolutegravir and +11kg in people taking TAF. Greater weight gain occurred in people with baseline viral load above 500,000 (+12.6kg) than lower levels. Women over 50 gained more weight than men under 50 (10.4 vs 8.8kg).
Dr Sophie Grabar and colleagues say that although weight gain in people with advanced HIV may be a ‘return to health’ effect, it might also be a symptom of long-term effects of uncontrolled HIV replication on the structure and healthy functioning of fat tissue. They recommend close monitoring of weight during the first year of treatment, together with careful selection of the antiretroviral regimen for people with advanced HIV or in the obese weight category.
Grabar S et al. Striking differences in weight gain after cART initiation depending on early or advanced presentation: results from the ANRS CO4 FHDH cohort. Journal of Antimicrobial Chemotherapy, published online 23 January 2023.