How Data on ART Adverse Events From IAS 2019 Will Affect My Practice

Cristina Mussini, MD

Head of Department of Infectious Diseases and Tropical Medicine
Full Professor of Infectious Diseases

Infectious Diseases Clinics, University Hospital
University of Modena and Reggio Emilia
Modena, Italy

Cristina Mussini, MD, has no relevant conflicts of interest to report.

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Released: September 4, 2019

The 10th IAS Conference on HIV Science in Mexico City, Mexico, was a very interesting meeting with many new data. One theme of interest was how presented results may influence regimen selection in patients initiating or modifying HIV therapy. Efficacy data for dolutegravir (DTG)-containing ART continue to be reassuring, but as these regimens are more widely used, we have started to see certain adverse events, the implications of which warrant our consideration.

NTD Risk With ART
One potential concern with DTG use is the proposed association with neural tube defects (NTDs). Preliminary data collected through May 2018 in the Botswanan Tsepamo study reported an NTD prevalence of 0.94% among women exposed to DTG at conception. Since then, the cohort has been expanded to include an additional 1257 women, representing an increase in coverage from approximately 45% to 72% of national births. In the updated analysis presented at IAS 2019 and published in the New England Journal of Medicine, 1 additional NTD case was reported among women receiving DTG at conception, reducing the overall prevalence from 0.94% to 0.30% in this population. However, this was higher than the NTD prevalence in women receiving non-DTG ART during conception (0.10%) and the general uninfected population (0.08%).

It should be noted that, outside of a single NTD case reported with periconception DTG exposure in the Antiretroviral Pregnancy Registry as of January 2019, data from Botswana are the only to observe this association. In Italy—and even across Europe—we must appropriately counsel our female patients about this very low risk when discussing treatment options.

ART and Weight Gain
Weight gain during HIV therapy was another important issue discussed at IAS 2019. Relevant to this conversation, data from 2 phase III trials of first-line ART—NAMSAL in Cameroon and ADVANCE in South Africa—were presented and published in the New England Journal of Medicine.

At Week 48, the NAMSAL study reported a significantly greater mean weight gain among patients receiving DTG plus lamivudine (3TC)/tenofovir disoproxil fumarate (TDF) compared with efavirenz (EFV) plus 3TC/TDF (5 vs 3 kg, respectively).

At Week 96, the ADVANCE study also reported significantly greater mean weight gain with DTG-based vs EFV-based ART (5-8 vs 2 kg, respectively). Particularly provocative was the amount of weight gain in women. Whereas increases seemed to plateau in men after Week 48, women continued to gain weight up to an average of 10 kg with DTG plus emtricitabine (FTC)/tenofovir alafenamide (TAF) and 5 kg with DTG plus FTC/TDF vs 3 kg with EFV/FTC/TDF.

Taken together, these data suggest that excessive weight gain seems to be related not only to treatment with DTG but also TAF, 2 drugs frequently used in preferred first-line regimens. Previous studies, including some presented earlier this year at CROI 2019, have signaled that this relationship may exist. ADVANCE now provides a well-designed, randomized comparison between TDF and TAF.

Survey data from a small subset of trial participants hinted that the weight gain was well accepted, even among women. However, this could be cultural, given that few women were overweight at the time of enrollment. It should be emphasized that these patients were predominantly African, precluding generalization of the findings to populations in Italy or Europe at large, but the magnitude of these potential increases is something very important to consider in any clinical practice.

Looking Ahead: Implications for My Practice
In my experience, many patients experience no weight gain on ART whereas others face a substantial increase and ask to modify their treatment. Although I will not hesitate to prescribe DTG or TAF for my patients, I will monitor them carefully for weight gain. Some may argue that the weight gain we are observing should be considered a return to wellness and represents the patient getting better, but I disagree. This amount of weight gain requires monitoring. We will also need to determine if a similar trend exists with bictegravir (BIC), which is only approved in combination with TAF. Unlike BIC, DTG can alternatively be combined with TDF if weight gain presents as an issue.

As with selection of any drug, adverse events should be kept in mind when prescribing ART. NNRTIs such as rilpivirine or older INSTIs such as raltegravir may not boast the heightened resistance barriers we see with newer guideline-recommended regimens, but their tolerability profiles may be the right match for a specific patient. In addition, if a patient develops an ART-related adverse event, one must be able to switch treatment strategies. For many patients, lifelong therapy can equate to more than 50 years of treatment, and ARV options are not one size fits all.

Join the Discussion
How will new data on ART-related adverse events affect your practice? Join the discussion by posting a comment. Then for more details on this and other key issues from IAS 2019, review more Conference Coverage including CCO’s summary slidesets and downloadable audio from a series of live Webinars.

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