Monthly dapivirine vaginal ring may help prevent HIV infection, particularly in women > 21 years old

EBM Focus - Volume 11, Issue 49

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Reference - N Engl J Med 2016 Dec 1 early online (level 2 [mid-level] evidence)

  • The majority of human immunodeficiency virus (HIV) infections in women are acquired via heterosexual contact.
  • In the Ring trial, a monthly vaginal ring containing dapivirine was shown to decrease the overall risk of HIV-1 infection by 2 cases per 100 person-years compared to placebo in healthy women in South Africa and Uganda.
  • There was no significant reduction in risk of HIV-1 infection in a subgroup analysis of women ≤ 21 years old.

In the United States, 84% of HIV infections in women are estimated to be transmitted through heterosexual contact (HIV Surveillance Supplemental Report 2012;17(4)). While use of condoms is an important part of preventing HIV transmission, there is a need for methods that women can control themselves. Pre-exposure prophylaxis (PrEP) is one of the major recent advances in HIV care. In men at risk for sexual acquisition of HIV, higher adherence to oral PrEP has been associated with a > 90% reduction in HIV risk (Sci Transl Med 2012 Sep 12;4(151):151ra125). In women, however, the results of PreP studies have been inconsistent (N Engl J Med 2012 Aug 2;367(5):399, N Engl J Med 2012 Aug 2;367(5):411, N Engl J Med 2015 Feb 5;372(6):509). This lack of efficacy is thought to be due to poor adherence in the study populations. An alternative strategy under investigation is the use of the antiretroviral drug dapivirine as a topical microbicide continuously delivered via a synthetic vaginal ring which can be self inserted and replaced on a monthly basis. In the Ring trial, 1,959 healthy women in South Africa and Uganda, aged 18 to 45 years, were randomized to dapivirine 25 mg vaginal ring vs. placebo ring distributed at monthly visits for up to 24 months. All women were given nonspermicidal condoms and received counseling regarding the risk of HIV infection as well as how to properly use contraceptives. The overall incidence of HIV-1 infection was 4.1 per 100 person-years with dapivirine vs. 6.1 per 100 person-years with placebo (hazard ratio [HR] 0.69, 95% CI 0.49-0.99) (NNT 50 per year). In a subgroup analysis of women > 21 years old, incidence of HIV-1 infection was 3.4 per 100 person-years vs. 5.5 per 100 person-years (HR 0.63, 95% CI 0.41-0.97). The absolute reduction in women ≤ 21 years old was 1.8 cases per 100 person-years and was not statistically significant. There were no significant differences between groups in overall rates of sexually transmitted infections, pregnancy, or grade 3 or 4 adverse events.

The results of this study are consistent with those of the ASPIRE trial that also examined the efficacy of the dapivirine-containing ring (N Engl J Med 2016 Feb 22 early online). In ASPIRE, use of the dapivirine-containing ring resulted in an absolute reduction of HIV-1 infection of 1.2 cases per 100 person-years (NNT 84 per year) compared to placebo in 2,629 healthy women living in Africa. As in the Ring trial, there is a wide confidence interval for the risk reduction (precluding a precise estimate) and no benefit seen in a subgroup analysis of women aged 18-21 years. An additional issue which needs to be addressed is the provision of protection for those who engage in nonvaginal sex. The development of HIV preventive strategies for women that do not require partner negotiation is highly desirable. The effectiveness of this intervention in women at high risk in different parts of the world may vary and will have to be studied in different regions before incorporation into public health HIV prevention strategies. Nonetheless, these results suggest that the dapivirine vaginal ring provides moderate protection against HIV infection and may provide an additional option for women trying to protect themselves from HIV.

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