Editor’s Note: The association between sexually transmitted infections (STIs) and HIV infection has always been a focal point in the medical community. With the promotion of pre-exposure prophylaxis (PrEP) strategies to prevent HIV infection, the impact of STIs on the effectiveness of PrEP has become an urgent issue to address. At the recently concluded Conference on Retroviruses and Opportunistic Infections (CROI 2024), researchers presented an oral abstract (Abstract 131) that explored the relationship between STI status and the effectiveness of two PrEP regimens (CAB-LA and daily oral TDF/FTC). Infectious Disease Frontier invited Dr. Hui Wang from The Third People’s Hospital of Shenzhen to provide an in-depth commentary on this study.
Study Summary
Cabotegravir Maintains Protective Effect in Bacterial STIs: The HPTN 083 Study
Background: Bacterially induced sexually transmitted infections (STIs) have been shown to facilitate the transmission and infection of HIV. In two large-scale randomized controlled trials, the long-acting formulation of cabotegravir (CAB-LA) proved superior to the daily oral regimen of tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for pre-exposure prophylaxis (PrEP), but the effect of PrEP in the presence of STIs had not been evaluated.
Methods: In one of the large randomized double-blind controlled trials, HPTN 083, STI events per 100 person-years were calculated from the start of double-blind enrollment to the last STI testing period before May 15, 2020, including repeat infection events. The Cox proportional hazards model was used with STI status as a time-varying covariate to explore potential interactions between STI status and the relative efficacy of CAB-LA vs. TDF/FTC. Participants were tested every six months for syphilis serologically, and for rectal and urethral gonorrhea and chlamydia nucleic acid, or upon symptoms/exposure to STI. The date of first diagnosed HIV infection was determined by an independent adjudication committee. Due to unknown exact dates of STI infection and treatment completion, intervals between each STI testing were divided into STI positive or negative periods. Intervals before and after each STI positive test were considered STI positive; all other intervals were considered STI negative. Different extrapolation methods for STI status were used in sensitivity analysis. The Cox model also included participants without follow-up.
Results: Among the 3,859 participants included in the analysis, the overall incidence of STIs was 50.7 cases/100 person-years. Of these, 1,562 individuals (40.5%) were diagnosed with STIs, and 691 individuals (17.9%) had multiple STIs, with 79% of all STIs occurring in 25% of the participants. There was no difference in STI incidence between the CAB-LA and TDF/FTC groups. In the m-ITT analysis (see Table 1), regardless of STI presence, the CAB-LA group had a lower HIV incidence rate compared to the TDF/FTC group [intergroup HR values were 0.37 and 0.31, respectively, with no significant association between STI and HIV infection (P=0.75)]. Sensitivity analysis yielded similar results.
Table 1: Cox Proportional Hazards Model Based on STI Status (n=4558)
Conclusion: In this large PrEP trial, where participants had a high incidence of STIs, CAB-LA maintained a strong PrEP effect among participants with bacterial STIs compared to TDF/FTC. Currently, there is no conclusion indicating that all PrEP medications can maintain protective effects against HIV in populations at high risk due to bacterial STIs. Therefore, it is necessary to investigate whether each PrEP medication can maintain a stable protective effect in the presence of STIs. Furthermore, future analyses on STIs should include data on herpes simplex virus-2 infections.
Expert Commentary
Pre-exposure prophylaxis (PrEP) is a novel and effective biological prevention method that uses antiretroviral drugs to prevent HIV infection. It is now recommended as an important HIV prevention strategy both domestically and internationally. Its target population includes individuals who engage in high-risk sexual behavior and are HIV antibody-negative, a group that is also often at high risk for STIs. Thus, researching whether STI infections affect the effectiveness of PrEP is equally important.
HPTN 083 is a large-scale, randomized, controlled, double-blind study, and the first worldwide to compare the efficacy of intramuscular injections of CAB-LA with daily oral TDF/FTC for HIV PrEP. The study recruited 4,570 men who have sex with men (MSM) and transgender women (TGW) who have sex with men across 43 sites in Argentina, Brazil, Peru, the United States, South Africa, Thailand, and Vietnam, with two-thirds under the age of 30 and 12% transgender individuals. Participants were randomly divided into two groups, each receiving both injectable and oral formulations, with one active drug and one placebo. The study found that the risk of HIV infection in the TDF/FTC group was almost three times that of the CAB-LA group, with an HR value of 0.31 for the CAB-LA group compared to the TDF/FTC group. This indicates that CAB-LA administered every 8 weeks is highly effective in preventing HIV infection among men and transgender women. Therefore, it is recommended for PrEP in guidelines both domestically and internationally.
While PrEP can prevent HIV infection, it does not prevent the transmission and infection of other STIs. The widespread use of PrEP may reduce the use of condoms among high-risk populations, potentially increasing the risk of STIs. The effectiveness of antiviral drugs can be influenced by many factors, such as drug-food interactions, adherence, other diseases, and individual differences. A reduction in antiviral drug efficacy could potentially lead to PrEP failure and subsequent HIV infection. Previously, there was no clear consensus on whether STIs affect the protective effect of PrEP, but this study indicates that both 8-weekly CAB-LA and daily oral TDF/FTC as PrEP methods have lower HIV incidence rates. Their protective effects are not affected by STIs, making them safe and effective PrEP methods.
References
Meredith Clement, et al. Cabotegravir Maintains Protective Efficacy in the Setting of Bacterial STIs: HPTN 083. CROI 2024; abstract 131.
Dr. Hui Wang
Chief Expert of the AIDS Medicine Center
The Third People’s Hospital of Shenzhen
