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IAS 2023 Australia
Australian Perspectives on Weight and Cardiometabolic Abnormalities From IAS 2023

Released: August 10, 2023

Don E Smith
Don E Smith, MD, FRCP (London) FAChSHM
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Key Takeaways
  • In Australia, where many persons living with HIV are treated with INSTI-based regimens, often combined with TAF, ongoing reports of weight gain with these regimens is concerning. Four key reports may allay fear in this arena.
  • Control of other metabolic abnormalities, including dyslipidemia and hypertension, is essential in aging persons living with HIV.

Australia is a region with a high rate of HIV diagnosis and treatment. At the end of 2021, it was estimated that 91% of those in Australia with HIV were diagnosed, 92% of people diagnosed were receiving HIV treatment, and among those on treatment, 98% had an undetectable HIV-1 RNA. As such, in our region, it is important to look at effects of antiretrovirals on health, particularly in our aging population.

This is my selection of the papers that will affect my practice in my HIV ambulatory clinic in Australia.

INSTI Plus TAF: Weight a Minute
Many persons living with HIV in Australia are being treated with second-generation integrase strand transfer inhibitors (INSTI)–based regimens, combined with tenofovir alafenamide (TAF), so any correlation with TAF or INSTI-based weight gain would be a concern for healthcare professionals in our region. Four important papers presented at the 2023 International AIDS Society conference may challenge our views about TAF/INSTI-associated weight gain.

Short and colleagues summarized the DEFINE study, which compared continuing INSTI plus TAF/emtricitabine (FTC) with switching to darunavir (DRV)/cobicistat (COBI)/FTC/TAF in people who had experienced ≥10% weight gain on their current therapy. Among the 103 participants, 60% were Black and 30% female, with a mean age of 45 years. After 48 weeks, there was no significant difference in weight between the groups (+0.63% with DRV/COBI/TAF/FTC vs -0.24% with INSTI/TAF/FTC), showing that replacing the INSTI-based antiretroviral therapy (ART) with another regimen did not affect weight.

Jürgen Rockstroh presented the results from a study in 599 treatment-naive persons living with HIV that randomized participants to doravirine (DOR)/islatravir (ISL) or bictegravir (BIC)/TAF/FTC. This study demonstrated noninferior virologic suppression with DOR/ISL but highlighted the lymphocyte toxicity seen with ISL 0.75 mg. However, it also showed that weight gain at 48 weeks was similar between the 2 groups: +3.45 kg with DOR/ISL vs +3.32 kg with B/F/TAF. Therefore, avoiding both TAF and INSTIs did not prevent weight gain.

Finally, Grace McComsey (Abstract 883) analyzed the results of 2 continue or switch to DOR/ISL strategies in patients suppressed either on any 2-3 drug ART (study P017) or on BIC/TAF/FTC (Study P018). Overall, there was a similar but small increase in weight for both arms in the P018 study but a significant increase in weight with DOR/ISL in the P017 study, driven by patients switching from regimens with tenofovir disoproxil fumarate (TDF) or efavirenz (EFV) or both.

Taken together, these studies indicate to me that there really is no weight-inducing potential for TAF or INSTI and that TDF and EFV are weight suppressants.

The Pressure’s on
That is not to suggest that weight gain, by whatever mechanism, is harmless. Within the RESPOND cohort (a consortium of 19 observational HIV cohorts in Europe and Australia), Byonanebye and colleagues noted that hypertension and dyslipidemia increased with increasing BMI.

This was also noted in the NAMSAL and ADVANCE trials, which were conducted in sub-Saharan Africa. In NAMSAL, grade 1 hypertension (>140/90 mm Hg) was significantly correlated with use of dolutegravir (DTG), age, sex, and BMI. In the ADVANCE trial, where hypertension was treated and antihypertensives were funded, DTG-associated hypertension was also noted, but blood pressure was similar across arms by Week 192.

Control of lipids is also important as our Australian cohort of persons living with HIV ages. In the REPRIEVE study (presented by Steven Grinspoon and colleagues), in participants older than 40 years of age with no known cardiovascular disease risk, intervention with pitavastatin was associated with a significant reduction of cardiovascular events by 35%. To me, this suggests that statins may be a useful tool in controlling cardiovascular risk in some people receiving ART.

Your Thoughts?
What are your perspectives on weight and ART? Share your comments in the discussion section.