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Professor of Medicine
Division of HIV, Infectious Diseases, and Global Medicine
University of California, San Francisco
Ward 86 HIV Clinic
San Francisco General Hospital
San Francisco, California
Monica Gandhi, MD, MPH, has no relevant conflicts of interest to report.
Rapid ART initiation at the time of diagnosis, or as soon as possible thereafter, is now a recommended strategy across the US and in international guidelines. How should we choose among regimens recommended for rapid initiation once we have identified that a patient is a good candidate? Guidance from the DHHS and IAS-USA are in agreement on 3 recommended regimens: bictegravir (BIC)/emtricitabine (FTC)/tenofovir alafenamide (TAF); dolutegravir (DTG) with either TAF of tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC) or FTC; and boosted darunavir (DRV) with either TAF or TDF plus 3TC or FTC (with a single tablet option of DRV/cobicistat (COBI)/FTC/TAF available). Here’s my approach for selecting among these regimens for rapid ART initiation in my patients.
Patients With No Prior Pre-Exposure Prophylaxis (PrEP)
For ART-naive patients who were not receiving PrEP prior to diagnosis, I generally recommend DTG plus FTC/TAF, DTG plus FTC/TDF, or BIC/FTC/TAF. The advantage of BIC/FTC/TAF is that it is available as a single-tablet regimen. However, for our Ward 86 clinic in San Francisco, at least, the DTG-based regimens offer a price advantage. We provide a 30-day starter pack for rapid ART initiation at no cost to the patient, and since we are paying for these packs, we chose DTG plus FTC/TAF. However, if patients have health insurance and they do not mind making a trip to the pharmacy rather than receive a DTG-based 30-day starter pack immediately from the clinic, we prescribe BIC/FTC/TAF if they prefer the ease of a single-tablet regimen.
Patients With Prior PrEP
For patients who were receiving PrEP prior to diagnosis, the concern would be that they experienced a breakthrough infection with viral strains that have either pre-existing or acquired resistance to one of the PrEP components, usually FTC (for example, via the M184V mutation). In this scenario, I start patients on boosted DRV-based regimens in combination with an INSTI. This combination could consist of DRV/COBI/FTC/TAF plus DTG, or DRV/COBI plus BIC/FTC/TAF. I recommend these patients start this combination approach while we await genotypic resistance test results. If the virus does not harbor any resistance associated mutations, then we can drop one of the drugs, either the INSTI or DRV, depending on their preference.
For patients with questionable adherence, I prefer DRV/COBI/FTC/TAF for rapid start, as DRV has one of the highest barriers to resistance of approved ART agents. With that in mind, for patients receiving PrEP at the time of diagnosis for whom I also have adherence concerns, I would recommend DRV/COBI/FTC/TAF plus an INSTI for rapid start and then drop the INSTI if resistance testing results do not demonstrate resistance associated mutations.
Women of Childbearing Potential
Finally, I am often asked how I handle rapid ART initiation in women of childbearing potential in the wake of concerns that were raised about the safety of DTG during conception. The DHHS guidelines have remained conservative regarding the use of DTG-based regimens in women of childbearing potential, classifying it as an alternative option for women of childbearing potential not on effective contraception or women trying to conceive. However, the WHO guidelines state that DTG can be prescribed in women of childbearing potential not on effective contraception or women trying to conceive, provided the patient is fully informed of the potential increased risk for neural tube defects (NTDs). At this point, I feel comfortable prescribing DTG for women of childbearing potential based on the updated analysis of the Tsepamo cohort, which revealed a much smaller risk for NTDs with DTG than initially signaled (0.3% vs 0.1% for non-DTG ART). Of note, the Tsepamo study was conducted in Botswana, where there is no folate supplementation of grains. The DHHS guidelines note that the overall risk of NTDs in the United States is low in the general population because of mandatory food folate fortification, and more data are needed to determine the risk of NTDs among infants born to women living in the United States and other countries with food folate fortification. Finally, the Antiretroviral Pregnancy Registry has found no safety signal with DTG use during pregnancy. In my opinion, concern about DTG safety during pregnancy is receding worldwide, and most clinicians who treat women with HIV are comfortable recommending these regimens after discussing the data and potential risks with their patients.
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