Professor of Medicine
School of Medicine
Site Leader, AIDS Clinical Trials Unit-Chapel Hill
University of North Carolina at Chapel Hill
Director, North Carolina AIDS Training and Education Center
Chapel Hill, North Carolina
Co-Director, HIV Services
North Carolina Department of Correction
Raleigh, North Carolina
David A. Wohl, MD, has disclosed that he has received consulting fees from Gilead Sciences, Merck, and ViiV and funds for research support from Gilead Sciences.
New data on ART regimens means new options for patients receiving older regimens. Although new is not always better, recently reported studies show that the latest crop of ART can be as effective but with less potential for drug-drug interactions and unfavorable metabolic outcomes. I recently reviewed new switch options with one of my established patients, an endearing woman who balances caring for her young son with earning an accounting degree. Long ago, she started therapy on lopinavir (LPV)/ritonavir (RTV) plus emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF). Later, the boosted PI was changed to darunavir (DRV) plus RTV and the FTC/TDF to FTC/tenofovir alafenamide (TAF); she has maintained a very stable virologic suppression.
I had last seen her at the end of 2017, when TAF and dolutegravir (DTG) were new and bictegravir (BIC) was still investigational. Since that visit, impressive data have emerged on these agents as part of 3-drug regimens, along with trial results on 2-drug combinations as well as a completely new antiretroviral agent. These data suggest a future free of the pharmacological boosters RTV and cobicistat (COBI).
Booster-Free Triple-Drug ART
Booster-free ART can be potent and have a high barrier to resistance. At IDWeek 2018, my colleagues and I presented 96-week data from the GS-1489 trial comparing 2 single-tablet regimens in ART-naive patients: BIC/FTC/TAF vs DTG/abacavir/lamivudine (3TC). Nearly 90% in each arm achieved virologic suppression, with no statistically significant difference between arms. Similar impressive outcomes were presented at Glasgow 2018 for the GS-1490 trial comparing BIC/FTC/TAF vs DTG plus FTC/TAF. In both studies, treatment-emergent resistance was not detected in any participant and the study agents were well tolerated with rare discontinuation for adverse effects. Furthermore, a study of switching from elvitegravir (EVG)/COBI/FTC/TDF, EVG/COBI/FTC/TAF, or RTV-boosted atazanavir plus FTC/TDF to BIC/FTC/TAF in virologically suppressed women yielded very high rates of suppression in both the switch and continue baseline ART arms.
Data presented at IAS 2018 suggested that triple-drug regimens may be overkill. The GEMINI trials showed that initiating dual therapy with DTG plus 3TC was noninferior to DTG plus FTC/TDF—a finding that would have astonished me back when my patient started on LPV/RTV plus FTC/TDF. The data perhaps most relevant to my patient came from the SWORD trials, in which virologically suppressed patients on standard ART were randomized to continue baseline ART vs switch to dual therapy with DTG plus rilpivirine (RPV). Approximately 90% in each arm maintained virologic suppression through Week 100. Again, tolerability was good in each arm, although more people in the 2-drug arm experienced drug-related adverse effects by Week 48 as reported by site investigators in these open-label trials.
The newest ART regimens are largely booster free. The NNRTI doravirine (DOR), which the FDA approved in August 2018, is active against viruses resistant to earlier NNRTIs. Like INSTIs, and unlike boosting agents, it has few clinically concerning drug–drug interactions. Data presented at IDWeek 2018 from the DRIVE-AHEAD trial showed that DOR/3TC/TDF was noninferior to, and better tolerated than, efavirenz/FTC/TDF in treatment-naive patients. We also heard at IAS 2018 that first-line DOR/3TC/TDF was more efficacious than RTV-boosted DRV plus 2 NRTIs. More important findings for my patient came from the DRIVE-SHIFT trial, which showed that DOR/FTC/TDF maintained virologic suppression while also leading to better lipid profiles in those switching from ART based on either a boosted PI, NNRTI, or EVG/COBI.
There is an exception to the boosterless trend—the single-tablet combination of DRV/COBI/FTC/TAF. This could have been more important in the pre-INSTI era. Nowadays, it is most relevant to those few people who cannot take DTG or BIC. The AMBER trial showed that initial therapy with the single-tablet combination works as well as DRV/COBI plus FTC/TDF over 96 weeks but with better renal and bone marker changes. In the EMERALD study, switching from a boosted PI–based regimen to DRV/COBI/FTC/TAF maintained virologic suppression over 96 weeks.
Counseling on Newer ART
Returning to my patient, I started our visit by counseling her that nothing was “broken” in her current regimen, but there were newer options that I wanted her to know about. These newer options could be expected to keep the virus under control plus lower the risks of dangerous drug interactions and worsened cholesterol levels. As I was emphasizing that we did not have to change anything today, she interrupted to ask, excitedly, if the new medication would be 1 pill per day. When I nodded, she said, “Let’s do it!”
How do you approach patients who have stable virologic suppression on an older ART regimen? Please share your thoughts by joining the conversation in the comments box.