Professor of Medicine
University Hospital Bonn
Department of Medicine I
Jürgen K. Rockstroh, MD, has disclosed that he has received consulting fees from Abivax, Gilead Sciences, Janssen, Merck, and ViiV and funds for research support from AbbVie, Gilead Sciences, Janssen, Merck, and Siemens.
At the 2019 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, Washington, we saw the highly anticipated results of the phase III DISCOVER trial comparing emtricitabine (FTC)/tenofovir alafenamide (TAF) vs FTC/tenofovir disoproxil fumarate (TDF) for daily oral pre-exposure prophylaxis (PrEP). This large randomized, double-blind trial enrolled 5387 cis-gender men who have sex with men (MSM) and transgender women at high risk of acquiring HIV infection, defined as 2 or more episodes of condomless anal sex in the previous 12 weeks, or with a diagnosis of rectal gonorrhea/chlamydia or syphilis in the previous 24 weeks. Prior PrEP use was permitted in the enrollment criteria.
Analysis of the primary endpoint revealed a very low rate of new incident HIV infections: 0.16 (7 in 4370 person-years of follow-up) in the FTC/TAF arm vs 0.34 (15 in 4386 person-years of follow-up) in the FTC/TDF arm. With an incidence rate ratio of 0.47 (95% CI: 0.19-1.15), FTC/TAF met the criteria for noninferiority vs FTC/TDF for daily oral PrEP (noninferiority upper bound of 95% CI: 1.62). These results once again strongly emphasize the efficacy of daily oral PrEP among cis-MSM and transgender women. Indeed, of the 22 identified new infections across both arms, 5 were suspected baseline infections and 15 were associated with low levels of tenofovir diphosphate in dried blood spots (suggesting adherence issues). There was a high rate (> 25%) of other sexually transmitted diseases (STDs) observed during the study follow-up, in particular chlamydia, gonorrhea, and syphilis, confirming that this study enrolled a patient population at high risk for acquiring STDs, including HIV infection.
Implications for PrEP in Germany
The DISCOVER trial results will further enhance the rollout of PrEP in Germany. Notably, the German government has recently passed a law that will lead to general reimbursement of PrEP through health insurance coverage. Currently, that entails coverage for generic FTC/TDF, which is available at a low cost of approximately 50 Euros per month. Whether reimbursement will also be considered for FTC/TAF as daily oral PrEP remains controversial. Whereas the 2 regimens demonstrated comparable efficacy in the DISCOVER trial, the safety data on renal and bone adverse events were more favorable for FTC/TAF. However, the overall safety reports were quite comparable with no significant differences in serious adverse events or discontinuations due to drug-related adverse events. Most likely, the considerable price difference between FTC/TAF and generic FTC/TDF will prevent widespread use of FTC/TAF in the near term. The exception may be among individuals with renal impairment or bone health concerns at baseline who wish to begin daily oral PrEP. Considering FTC/TAF vs FTC/TDF will be particularly important for individuals with a decreased glomerular filtration rate or a contraindication for TDF use, including those with diabetes and/or hypertension and renal organ involvement.
Join the Discussion
What did you take away from the DISCOVER trial results? Join the discussion by posting a comment below. For more details on this and other key studies from CROI 2019, download and review CCO’s summary slidesets and listen to audio from a series of postconference Webinars. And check back soon for more expert commentary and CME-certified education featuring even more studies from CROI 2019.