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While you are working for one month in a health center in South Africa, a 19-year-old woman comes to the clinic and asks for your advice: She is HIV-negative, her partner is HIV-positive, and she is unsure whether he is taking his antiretroviral medications. Is there anything she can do to prevent her from acquiring HIV?
Preexposure prophylaxis (PrEP) with oral tenofovir-emtricitabine has been found to be effective in men who have sex with men, both in randomized-controlled trials and in real-world effectiveness studies. However, the efficacy of PrEP in women has been inconsistent, especially in young women in sub-Saharan Africa. Studies of vaginal tenofovir gel and oral tenofovir-emtricitamine in women have failed to consistently demonstrate a reduction in the risk of HIV acquisition. The limited efficacy was thought to be attributed to poor adherence and possibly a lower concentration of tenofovir in the female genital tract.
Two studies appearing in this week’s NEJM highlight a new approach to prophylaxis against HIV. Both the Ring study and the Aspire study were randomized, double-blind, placebo-controlled trials conducted in sub-Saharan Africa. These trials examined the effectiveness of a monthly self-inserted vaginal ring that contains sustained-release dapivirine, a non-nucleotide reverse transcriptase inhibitor, in healthy, nonpregnant, HIV-uninfected women aged 18-45 years who were engaged in regular sexual activity. All participants received treatment for sexually transmitted infections and a standard HIV prevention package (including regular HIV testing, counseling, and condoms).
The primary outcome in both studies was new HIV infections. In both studies, the HIV incidence rate was lower in the dapivirine group than in the placebo group. In the Ring study, incidence rates were 4.1 vs. 6.1 per 100 person-years (relative reduction, 31%) and in the Aspire study, the rates were 3.3 vs. 4.5 per 100 person-years (relative reduction, 27%). In the Aspire study, the ring did not significantly reduce HIV incidence in women ≤21 years old, but was associated with a 61% relative reduction in women >21. Adherence to treatment was good in both studies, based on pre-specified levels of plasma dapivirine concentrations and remaining dapivirine levels in returned rings.
In prior studies, poor adherence to PrEP therapies was hypothesized as the primary reason for treatment failure. The finding from these two studies that the dapivirine ring only reduced HIV acquisition by approximately 30% suggests that the ring itself had limited efficacy or that the thresholds for adherence selected by the investigators were insufficient to identify poor adherence. Many will question whether a 30% reduction in HIV incidence is sufficient to deem this prophylaxis strategy a success. Additionally, the reduced efficacy in younger women remains a challenge.
Although population-based implementation of the dapivirine rings would decrease the burden of new HIV infections, this strategy provides minimal reassurance to individual patients who remain at high risk of contracting HIV, even with a dapivirine ring. In an accompanying editorial, Dr. Adaora A. Adimora from the Institute for Global Health and Infectious Diseases at the University of North Carolina School of Medicine concludes, “The past few years have yielded substantial progress in strategies for the prevention of HIV infection. Nevertheless, considerable work will be required to achieve safe, effective, affordable HIV prevention for all women at risk.”
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Rebecca is a 2016-2017 NEJM Editorial Fellow and a hospitalist at Massachusetts General Hospital. She graduated from Columbia University College of Physicians and Surgeons in 2013 and completed internal medicine residency at Massachusetts General Hospital in 2016. Her interests include medical education, quality improvement, patient safety, health care delivery innovation, and teaching value in health care.