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Scientists in South Africa and Cameroon conducted two randomized clinical trials of dolutegravir-based regimens. These trials have yielded important safety information as well as data about weight gain. The findings from these studies confirm general trends that we will report on later in this issue of TreatmentUpdate.
In South Africa, scientists conducted a randomized 96-week study of the following once-daily regimens used to initiate HIV treatment (ART):
Study coordinators enrolled 1,053 HIV-positive people who initiated ART with one of the above regimens. Notably, nearly 60% of participants in ADVANCE were women and 99% were black.
Not surprisingly, all three regimens worked well. We won’t explore the effects of the medicines on viral load and CD4+ cell count, as such effects have been well established in clinical trials beginning nearly a decade ago for dolutegravir and even longer for efavirenz. Instead, we focus on some safety issues and weight.
Overall, dolutegravir-containing regimens were well tolerated. There were generally no significant differences in sleep quality and the time spent sleeping among the different regimens. However, the scientists stated that “there were slightly more reported cases of [severe or very severe] insomnia in the TAF-based group than in the other groups but no discontinuation of the trial regimen due to insomnia.”
As detailed in TreatmentUpdate issue 233, there have been reports of five babies born to HIV-positive mothers in the southern African country of Botswana who were born with a type of birth defect called neural tube defects. All mothers were taking dolutegravir at the time of conception.
In the ADVANCE study, a total of 78 women became pregnant; 50 of them were taking dolutegravir during pregnancy. None of their babies were born with neural tube defects. Ten percent of the pregnancies are ongoing.
According to the scientists, “absolute weight gain and the percentage of patients in whom obesity emerged during treatment were highest in the TAF-based group (6 kg, 14% new obesity), but the values in the TDF-based group (3 kg, 7% new obesity) were also higher than those in the standard-care group [efavirenz: 1 kg, 6% new obesity].”
Furthermore, scientists added that “weight gain was significantly higher in female than in male patients across all three groups with no clear plateau in the increase.”
Obesity tended to occur by week 48 and was associated with the following factors upon study entry:
In Cameroon, another randomized clinical trial called NAMSAL enrolled 613 HIV-positive people, a majority of whom (66%) were women. All participants were initiating ART that consisted of one of the following regimens:
All medicines were taken once daily and data were reported after 48 weeks.
On average weight gain was observed in more participants who took dolutegravir than low-dose efavirenz, as follows:
A total of 25 women became pregnant during the study, 13 who were taking dolutegravir and 12 who were taking efavirenz. No birth defects were found in their infants.
The data from ADVANCE and NAMSAL show that commonly used regimens in parts of sub-Saharan Africa these days are associated with weight gain, in particular, the combination of dolutegravir and TAF. However, other factors also associated with weight gain were as follows:
The fact that having a lower CD4+ cell count and a higher viral load were both associated with weight gain suggests that HIV does something to the immune system that increases the risk of weight gain. This finding is yet another reason to initiate ART early in the course of HIV infection.
—Sean R. Hosein
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