What’s New in HIV Treatment

Key Takeaways

• Integrase strand transfer inhibitor–based regimens remain the most highly recommended first-line HIV treatment options worldwide, with long-term data showing excellent outcomes.
• Weight gain with antiretroviral therapy remains an area of intense investigation.
• Long-acting antiretroviral therapy continues to demonstrate high efficacy as a switch regimen, with several baseline factors predictive of risk of virologic failure.

The HIV treatment landscape saw continued progress through 2022 with exciting new data on both existing and emerging strategies across various stages of HIV therapy, from initial antiretroviral therapy (ART) to switch strategies for people with viral suppression on their current regimen, as well as options for people who have extensive treatment experience and multiclass drug resistance. 

However, it is important to consider advances in therapeutic HIV research within the context of the current state of the global HIV epidemic. At the 24th International AIDS Conference in Montreal, Canada, the Joint United Nations Programme on HIV/AIDS (UNAIDS) July 2022 update on the state of the HIV epidemic worldwide delivered a somber picture: It showed that progress in HIV treatment and prevention is faltering worldwide, with dwindling resources and widening inequities. One result is that rates of new HIV infections have increased across many regions that had previously experienced declines. This situation has arisen because of multiple overlapping crises—including the COVID-19 pandemic—that have overwhelmed healthcare capacity and dramatically set back the global response to HIV/AIDS. The update from UNAIDS July 2022, appropriately titled “In Danger,” serves as a call to action and provides an imperative to get back on track with HIV care, including through application of the latest data to advance care and expand access.

So, what have we learned about HIV treatment in 2022?

Initial ART
Integrase strand transfer inhibitor (INSTI)–based regimens (eg, bictegravir [BIC] and dolutegravir) continue to be the most highly recommended first-line therapy options worldwide, with long-term data showing excellent outcomes. Five-year data are now available for BIC/emtricitabine (FTC)/tenofovir alafenamide (TAF) as a single pill combination and show high rates of long-term virologic suppression. The BIC/FTC/TAF combination also works well over time in patients with a history of the M184V/I mutation, with no emergence of new mutations if adherence is maintained. 

However, weight gain and associated metabolic effects are still a concern with the newer-generation INSTIs, especially when used in combination with TAF, as shown by the ADVANCE trial and other studies. Several studies are underway to determine if a switch to other regimens, including doravirine-based (Do IT study) or darunavir-based (DEFINE study) regimens, improves weight gain outcomes in people who experience excessive weight gain on regimens containing INSTIs plus TAF. 

Switch to Long-Acting (LA) ART
In 2022, we also saw more data from studies evaluating a switch to LA injectable cabotegravir (CAB) plus rilpivirine (RPV), including the FLAIR and ATLAS trials examining monthly dosing of LA CAB plus RPV and ATLAS-2M comparing monthly dosing with dosing every 2 months. All 3 trials showed high virologic suppression rates among participants who switched to LA ART from virologically suppressive oral regimens.

Virologic failure was infrequent in the trials, but risk factors for failure included RPV-associated resistance mutations at baseline, high BMI (≥30 kg/m²) at baseline, HIV-1 subtype A1/A6, and low RPV trough levels at Week 8 of treatment. However, in an analysis of the 3 baseline factors, it was only in the presence of ≥2 such factors that the risk of virologic failure increased. 

Recent demonstration projects examining a switch to LA CAB plus RPV in patients with adherence challenges also have shown high virologic suppression rates. 

ART for Multidrug-Resistant HIV
It is reassuring that new options also are emerging for people who have HIV with multiclass drug resistance, a critical population often with very limited treatment options. 

For those who have virus that is CCR5 tropic, maraviroc continues to be an option that can be added to an optimized background regimen to help with viral suppression.

Two newer options for multidrug-resistant HIV are fostemsavir, an oral HIV-1 gp120–directed attachment inhibitor that is given twice daily, and ibalizumab, a CD4-directed postattachment HIV-1 inhibitor that is given intravenously over a 30-second push every 2 weeks, both of which can serve as effective and critical components of a salvage regimen.

Finally, lenacapavir (LEN), an LA capsid inhibitor given as an SC injection every 26 weeks, is being studied in treatment-naive patients (CALIBRATE trial) and in heavily treatment–experienced patients with multiclass drug resistance (CAPELLA trial). Results from the CAPELLA trial showed that, for patients with multiclass drug-resistant HIV, oral LEN added to a failing regimen reduced HIV-1 RNA levels significantly more than the failing regimen plus placebo over a 14-day functional monotherapy period. All patients were subsequently switched to an optimized background regimen plus SC LEN every 26 weeks, and at Week 52, 78% of patients (N = 72, including 32 patients from a nonrandomized cohort) had HIV-1 RNA <50 copies/mL. 

LEN was approved in Europe in August 2022 for use in combination with other antiretroviral drugs for people with multidrug-resistant HIV lacking an available suppressive regimen, and it is currently under review by the FDA for the same purpose, with an expected decision in late December 2022.

Your Thoughts?
What are your thoughts on recent changes in the HIV treatment landscape? How are you applying the latest data in your practice? Join the discussion by posting a comment.