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Department of Internal Medicine
National Taiwan University Hospital
Chien-Ching Hung, MD, PhD: consultant: Gilead Sciences; non-CME/CE services: Gilead Sciences; researcher: Gilead Sciences, MDS, ViiV Healthcare.
DoxyPEP: Doxycycline PEP for STI Prevention in MSM and TGW Receiving HIV PrEP or With HIV
New diagnoses of bacterial sexually transmitted infections (STIs) such as syphilis, gonorrhea, and chlamydia are increasing, particularly among men who have sex with men (MSM) and transgender women (TGW). This phenomenon may be exacerbated by progress of HIV treatment and prevention, including pre-exposure prophylaxis (PrEP) and postexposure prophylaxis (PEP). Risk compensation with declines in condom use, treatment optimism about the benefits of improved antiretroviral therapy (ART), and increases in STI testing also have contributed to these trends. Improved accessibility to testing and treatment of STIs is an important strategy to control these infections.
A prior open-label, randomized substudy of ANRS-IPERGAY used doxycycline 200 mg taken as a single oral dose (vs no doxycycline) within 24 hours of sex as PEP for STIs. Doxycycline was shown to reduce the occurrences of a first episode of syphilis by 63% and chlamydia by 70% among MSM who participated in this event-driven trial.
Whether doxycycline as PEP could reduce the incidences of bacterial STIs remained less clear for MSM or TGW with HIV. That’s why I was interested in the doxycycline PEP (DoxyPEP) trial presented at AIDS 2022. This trial was conducted in HIV and STI clinics in San Francisco and Seattle, where the background prevalence of STIs is as high as 30% among MSM and TGW.
This trial planned to enroll 390 MSM and TGW receiving HIV PrEP and 390 MSM and TGW with HIV who reported having ≤1 STI and condomless sex with ≥1 male partners in the past 12 months. Participants were randomized in a 2:1 ratio to receive doxycycline 200 mg as PEP or no PEP within 72 hours of condomless sexual contact; they were monitored every 3 months for infection with Neisseria gonorrhoeae, Chlamydia trachomatis, and syphilis. The primary endpoint was ≥1 STIs during a quarterly follow-up.
Trial Stopped Early for Effectiveness of Doxycycline
This trial was stopped early because of significant effectiveness observed in participants randomized to receive doxycycline as PEP. MSM and TGW receiving HIV PrEP and people with HIV who received doxycycline as PEP had a 66% and 62% risk reduction, respectively, for STIs compared with those who did not receive doxycycline. The risk reduction was observed for syphilis, gonorrhea, and chlamydia. Doxycycline appeared to be well tolerated.
The difference in terms of risk reduction for preventing gonorrhea between this study and the substudy of ANRS-IPERGAY (HR: 0.83; 95% CI: 0.47-1.47; P = .52) might be related to the difference in the prevalence of N gonorrhoeae with resistance to doxycycline. Population-level N gonorrhoeae with tetracycline resistance was estimated at 20% in the United States and 56% during the IPERGAY trial in France.
Implications for the Asia-Pacific Region
Given the high burden of bacterial STIs and scaling up of HIV PrEP in this Asia-Pacific region, the impact of doxycycline as PEP for MSM and TGW irrespective of HIV status will be significant in terms of reducing the incidences of syphilis and chlamydia among the at-risk populations. However, in this region, the data on the resistance of N gonorrhoeae to tetracycline are limited compared with that for ceftriaxone, cefixime, azithromycin, and ciprofloxacin. More surveillance studies are needed to examine the long-term impact on the emergence of resistance of bacteria causing STIs if doxycycline PEP is widely adopted to prevent bacterial STIs among MSM and TGW.
ALLIANCE: TAF vs TDF for HIV and HBV
Many Asia-Pacific countries and African countries are of higher intermediate (5%-7.99%) or high endemicity (≥8%) for hepatitis B virus (HBV) infection. Because of shared transmission routes, people with HIV are at higher risk for HBV infection.
To prevent HBV-related complications in people with HIV/HBV coinfection, current guidelines recommend early initiation of combination ART containing tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF). Two earlier randomized, double-blind phase III trials demonstrated that TAF is noninferior to TDF in achieving plasma HBV DNA <29 IU/mL at Week 48 among people with hepatitis B e antigen (HBeAg)-negative or HBeAg-positive HBV monoinfection, with significantly smaller decreases of bone mineral density and smaller increases of serum creatinine. Although switch of TDF-containing ART to coformulated elvitegravir/cobicistat/TAF/emtricitabine (FTC) maintained high rates of HIV and HBV suppression with improvement of bone mineral density and proteinuria among people with HIV/HBV coinfection, data remain limited on whether TAF-containing ART is noninferior in HIV virologic efficacy to TDF-containing ART in treatment-naive persons with HIV/HBV coinfection. A report at AIDS 2022 addressed that question.
ALLIANCE is a multicenter, randomized, controlled phase III trial of coformulated bictegravir (BIC)/FTC/TAF vs dolutegravir (DTG) + FTC/TDF as initial treatment in people with HIV/HBV coinfection. In total, 243 people with HIV/HBV coinfection who were naive to both HIV and HBV treatment were randomized 1:1 to receive BIC/FTC/TAF or DTG + FTC/TDF. Of these, 88.1% were Asian patients.
HIV and HBV Endpoints
At Week 48, BIC/FTC/TAF was shown to be noninferior to DTG + FTC/TDF in achieving plasma HIV-1 RNA <50 copies/mL in the FDA Snapshot analysis. This was not an unexpected result. However, the results regarding the efficacy against HBV were surprising to many.
Implications for the Asia-Pacific Region
Given the high proportion of Asian participants enrolled on the trial, the results would be most relevant to the Asia-Pacific region, where chronic HBV infection remains a prevalent hepatic comorbidity in people with HIV.
Although the findings of superiority of 48-week treatment with BIC/FTC/TAF to DTG + FTC/TDF with respect to HBV DNA <29 IU/mL remain unexplained, long-term follow-up to observe the impact of TAF-containing ART on the functional cure of HBV and hepatic outcomes of interest is warranted.
Before definite cure of HBV infection is available, how to make TAF more accessible to people with HIV/HBV infection is another pressing issue in the long-term successful management of chronic HBV infection.
How relevant are these observations to you and your practice? Leave a comment and join the conversation.