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AIDS 2024
Insights From AIDS 2024: Optimizing ART in Australia

Released: August 20, 2024

Expiration: August 19, 2025

Don E Smith
Don E Smith, MD, FRCP (London) FAChSHM
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Key Takeaways
  • PASO-DOBLE results show that switching to DTG/3TC or BIC/FTC/TAF was safe and effective for people with HIV who are virally suppressed, with people receiving BIC/FTC/TAF gaining moderately more weight than people receiving DTG/3TC.
  • Among treatment-experienced people with HIV, data from the SOLAR-3D, SOUND, and VISEND studies, as well as a study in Haiti, show that virologic failure and treatment-emergent resistance with INSTI-based regimens are very rare, even in people with a history of resistance associated mutations.

Perhaps the key theme emerging from the 2024 IAS World AIDS Conference (AIDS 2024) was how HIV care has become more focused on treatment optimization than ever before. This came about because of the potency and tolerability of modern antiviral agents. The theme of antiretroviral therapy (ART) optimization is of particular relevance to Australia, where nearly one half of people with HIV are older than 50 years of age. As these people age, changes to their ART regimens may be needed to address comorbidities and ensure good quality of life while maintaining viral suppression. 

ART for People With Non-AIDS Comorbidities
A common concern among people with HIV is weight gain caused by their ART regimen. One of the conference presentations that sought to address this was the Spanish PASO-DOBLE (GeSIDA 11720) study of 553 people with HIV who were virologically suppressed on older ART combinations, with no known drug resistance or hepatitis B infection.

Participants were randomized to switch to either dolutegravir (DTG)/lamivudine (3TC) or bictegravir (BIC)/emtricitabine (FTC)/tenofovir alafenamide (TAF). Investigators reported that viral suppression rates were high—93.1% and 89.9% for the DTG/3TC and BIC/FTC/TAF arms, respectively. Reassuringly, no cases of viral failure with resistance were seen in either arm. These results suggest that the 2-drug combination is adequately potent in this population.

The study also provides a much-needed direct comparison of weight change after switching to DTG/3TC or BIC/FTC/TAF. There was a small but significant difference in weight gain of almost 1 kg in the BIC/FTC/TAF arm compared with the DTG/3TC arm, mainly driven by subjects coming off tenofovir disoproxil fumarate (TDF)–based therapy. However, the extent of the changes in weight experienced by people who switched to DTG/3TC are inconsistent among studies such as SALSA, TANGO, and PASO-DOBLE, and it is still unclear whether ART switch can address weight gain.

ART for Treatment-Experienced People With HIV
Another concern among older people with HIV is viral resistance. Many older people with HIV received treatment with early ART that had lower barriers to resistance, making current and prior HIV resistance mutations a major concern when considering an ART switch for treatment optimization.

To this end, investigators presented the 144-week results from the SOLAR 3D study, among heavily treatment–experienced people with HIV who had prior or current 3TC resistance. This open-label study compared 50 people with no past M184V/I resistance mutations with 50 people with a known history of M184V/I mutations. Viral suppression rates were similar between people with and without a history of 3TC resistance and regardless of virologic failure of past regimens (94.9% vs 92.3%). Of note, no treatment-emergent resistance was found. 

However, resistance testing is not always readily available, making it difficult for treatment-experienced people with HIV who are virologically suppressed to change their ART regimens, even if they are dissatisfied with it in other ways. In Australia, healthcare professionals are often reluctant to switch people to a simplified ART regimen without first obtaining a background resistance profile.

To address this concern, a few studies at AIDS 2024 investigated the rate of ART resistance after ART switch in people with more extensive treatment experience, who did not have prior resistance testing.

First, a prospective, randomized, noninferiority trial at the GHESKIO centers in Haiti assessed a switch from an ritonavir-boosted, protease inhibitor–based ART regimen to BIC/FTC/TAF in people with a history of first-line ART failure. Despite the high rate of nucleos(t)ide reverse transcription inhibitor (NRTI) resistance in this setting, investigators found that switching to BIC/FTC/TAF had noninferior efficacy vs continuing on a ritonavir-boosted, protease inhibitor–based second-line regimen.

Next, although only a small pilot study, the SOUND study investigated the important question of whether switching to DTG/3TC is safe and effective for people with virologic suppression and unknown resistance history. Investigators reported that, despite retrospectively detecting 184V mutations in 6 of the 40 participants and integrase strand transfer inhibitors resistance associated mutations in 2 participants, no cases of virologic failure were seen.

Finally, in a similar vein, the VISEND study evaluated the efficacy of switching to DTG plus either 3TC/TDF or FTC/TAF in people with HIV after virologic failure of nonnucleoside reverse transcriptase inhibitor–based regimens. In particular, this study sought to address the long-term outcomes of switching to a DTG-based regimen with a maintained NRTI backbone. The 144-week results of this study showed that, despite high baseline NRTI resistance, switching to DTG plus either 3TC/TDF or FTC/TAF was associated with high rates of virologic suppression, and no resistance to DTG was observed. 

Together, these results are particularly significant, as they bring us one step closer to having more options for treatment simplification and optimization for treatment-experienced people with HIV.

Conclusion
In Australia, where government-funded ART, coupled with increased public awareness, has led to impressive rates of viral suppression—98.4% according to the ACCESS dataset of 6444 people with HIV—these major studies from AIDS 2024 represent the next steps in ART optimization and continuing improvement of quality of life for people with HIV, especially as this population grows older.

Your Thoughts?
How have these studies affected your perception of the need for resistance testing before ART switch? Leave a comment to join the discussion!