French study finds strikingly less weight gain when HIV treatment is begun early

In the early 1980s, researchers recognized that HIV was linked to weight loss. In some people this weight loss could become life threatening. In that era in parts of Sub-Saharan Africa, HIV-associated weight loss was also called “slim disease.” Chronic HIV infection can contribute to weight loss in a number of ways:

• by making the body more susceptible to intestinal infections (leading to intestinal inflammation, diarrhea and malabsorption)
• by increasing the nutritional demands arising from fighting life-threatening infections
• by changing the way the body stores and uses energy

SIV (simian immunodeficiency virus) is a virus that is related to HIV. SIV can also cause weight loss and an AIDS-like condition in susceptible monkeys.

Impact of HIV treatment

The widespread availability of effective HIV treatment (ART) has transformed chronic HIV infection. Initiating ART helps to lower the amount of HIV in the blood. Usually, three to six months after initiating ART, the amount of virus in the blood falls to such a low level that it cannot be accurately assessed with routinely used lab tests. Such a low or suppressed level of HIV is commonly called “undetectable.” As HIV levels remain suppressed with continued treatment, the immune system is able to repair itself sufficiently such that the risk of AIDS-related infections becomes extremely rare. The impact of ART is so transformative that researchers forecast that many ART users will have near-normal life expectancy.

Studies in the current era have found that initiation of ART is associated with some degree of weight gain. On balance, gaining a few pounds or a couple of kilos of weight is a good thing, as untreated HIV is associated with weight loss. Indeed, researchers refer to modest weight gain associated with ART to be a “return to health.” However, some studies have reported that the weight gained can be excessive—a 10% or more increase in pre-ART body weight that can cause some people to be classified as overweight or obese.

A French study

A team of researchers with the French Hospital Database HIV Cohort explored this issue. The database has been in operation since 1989 and currently monitors more than 100,000 people with HIV. It has produced useful analyses about the health of people with HIV in the past.

The researchers recently analysed information in the database collected between 2012 and 2018. They focused on nearly 13,000 people who initiated ART during that time. The researchers compared the results of ART initiation over several years in two groups of people; they defined these groups as follows at the time they started ART:

• early initiators – people with CD4+ counts greater than 350 cells/mm³ and an HIV viral load less than 100,000 copies/mL
• late initiators – people with AIDS or a CD4+ count less than 200 cells/mm³

An average of 30 months after initiating ART, researchers found that 35% of participants had gained a significant amount of weight (10% or more of their pre-ART body weight). The researchers found the distribution of this weight gain striking, as follows:

• 5,794 people: early initiators – 21% gained a significant amount of weight
• 3,106 people: late initiators – 63% gained a significant amount of weight

The researchers found that people who were underweight or obese prior to starting ART were at significantly increased risk for weight gain once they initiated ART.

Most significant weight gain occurred during the first year of ART initiation. This should be reassuring for patients and their care providers—significant weight gain does not occur indefinitely.

Emphasizing early initiation of ART

In the past decade, leading treatment guidelines in high-income countries have recommended early initiation of ART for at least two reasons. The first is that effective ART helps to preserve the immune system and significantly reduces the risk of serious HIV-related infections. The second is that well-designed studies have found that people who achieve and maintain an undetectable viral load do not pass on HIV to their sexual partners.

If the French study’s results are confirmed by other research teams, perhaps another reason for initiating ART early will be to help reduce the risk of unnecessary weight gain.

Study details

The French team focused on 12,773 people who had not previously taken ART. On average, they underwent five weight measurements during the study.

Overall, 75% of participants were men and 25% were women. The researchers stated that they “excluded transgender participants because of the interaction of hormone therapy with weight, and pregnant [people were excluded at the point where pregnancy was confirmed].”

The average profile of participants at the time they entered the study was as follows:

• age – 38 years (most people were between the ages of 30 and 48); early initiators were younger (36) compared to late initiators (42)
• key populations: gay, bisexual and other men who have sex with men (MSM) – 48%; heterosexual people – 45%; people who injected drugs – 2%
• 26% of participants were from sub-Saharan Africa while the remainder were from France
• body mass index (BMI) – 23 kg/m²
• the researchers classified people according to their weight in the following way: underweight – 7%; normal weight – 62%; overweight – 22%; obese – 8% (late initiators were more likely to be underweight than early initiators – 13% vs. 5%)
• CD4+ counts: early initiators – 520 cells/mm³; late initiators – 105 cells/mm³ (most people had CD4+ counts between 44 and 167 cells)
• viral load: early initiators – 20,000 copies/mL; late initiators – 160,000 copies/mL

Note that percentages do not total 100 due to rounding.

Commonly used regimens

At the time combination HIV therapy was initiated, commonly used classes of drugs were as follows:

• 42% used protease inhibitors – most commonly darunavir (sold as Prezista and in Prezcobix and generic formulations)
• 33% used an integrase inhibitor – most commonly dolutegravir (Tivicay and in Dovato and Triumeq) or elvitegravir (in Genvoya and Stribild)
• 25% used a non-nuke – most commonly rilpivirine (in Complera and Odefsey)

Common HIV treatments used in addition to the above drugs included the following:

• 78% used tenofovir DF + FTC (a combination sold as Truvada and available in generic formulations)
• 16% used abacavir + 3TC (a combination sold as Kivexa and available in generic formulations)
• 6% used TAF (tenofovir alafenamide; sold as Descovy and in Genvoya and Odefsey)

Results

After an average of 30 months, researchers found weight gain of 10% of more distributed as follows:

• early initiators – 21%
• late initiators – 63%

The researchers started that “higher risks [of significant weight gain] were observed for women, non-MSM, underweight [people], those with more profound immunodeficiency, higher viral load and prior AIDS.”

The researchers did not find differences in weight gain among people who had different AIDS-related infections and conditions.

Differences in effects of different medicines on weight

Although the researchers stated that they found different risks of weight gain depending on the drugs used, we caution readers that this was not a randomized controlled trial. It was an observational study. The reasons that some people were prescribed certain regimens is not clear. Observational studies are good at finding overall trends or associations but can sometimes cause researchers to inadvertently draw biased conclusions. Therefore, recommendations about which individual drugs or which classes of drugs to use are best left to researchers who review and write treatment guidelines. For these guidelines, data from well-designed, randomized controlled studies are primarily used.

Weight changes over time

In the French study, overall, participants gained 8 kg of weight. Most weight gain occurred during the first 12 months of the study. The researchers stated that “weight gain was significantly larger among women, people originating from Sub-Saharan Africa, non-MSM, underweight [people], those with more profound immunodeficiency, higher viral load and prior AIDS…”

As with the previous analysis, there were no differences in weight gain among people who had different AIDS-related infections and conditions.

As mentioned earlier, weight gain was more significant among people who initiated ART late (10 kg) vs. those who initiated ART early (3 kg).

Bear in mind

• The researchers found that, on average, weight gain was relatively modest among people initiating ART early rather than late.
• Most weight gain occurred during the first 12 months after ART is initiated.

Late diagnosis issues

The researchers stated that part of the reason for increased weight in people who initiated ART late “may simply be a return to health, and the clinical consequences, if any, could be limited to those who become obese.” They added, “However, it would be preferable not to be diagnosed late because of the unknown consequences of rapid weight gain associated with treatment initiation and the already known long-term consequences of [seeking care when the immune system is greatly weakened] ….”

The researchers draw attention to a previous study published in 2013 with data also from France. In that study, scientists monitored more than 11,000 people with HIV who sought care late. The scientists reported that even after initiation of ART, “late presenters had a higher risk of death than those presenting [early]. This increased risk of death was observed up to four years of follow-up.”

The researchers with the current study on weight gain encourage doctors and nurses to monitor the weight of their patients, particularly in the first year after ART has been initiated. The researchers stated that nearly 30% of people diagnosed with HIV in France in 2021 had profound immune deficiency. So, this particular population would require close monitoring of weight once ART was initiated.

Note well

Although the current French study found a difference in weight gain based on whether treatment was initiated early or late, the difference was not absolute. Some people who initiated ART early still gained significant weight and some who initiated ART late did not. Further research is required to uncover the reasons for significant weight gain and possible interventions to minimize this.

Like the vast majority of studies in the past several years on ART and weight gain, the French study did not collect socio-economic, physical activity and dietary data.

The reason(s) for significant weight gain are not known (regardless of whether people initiated ART early or late).

The French study is an important step forward in trying to understand weight gain that is associated with ART. Hopefully, other large databases will assess their patients to confirm the findings.

By Sean R. Hosein

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