Safety and efficacy of a dapivirine vaginal ring for HIV prevention in women
Nel, A.; Van Niekerk, N.; Kapiga, S.; Bekker, S.-G.; Gama, C.; Kamali, A.; Kotze, P.; Louw, Cheryl; MAbude, Z.; Miti, N.; Kusemererwa, S.; Tempelman, H.; Carstens, H.; Devlin, B.; Isaacs, M.; Malherbe, M.; Mans, W.; Nuttall, J.; Russell, M.; Ntshele, S.; Smit, M.; Solai, L.; Spence, P.; Steyler, J.; Windle, K.; Borremans, M.; Resseler, S.; Van Roey, J.; Parys, W.; Vangeneugden, T.; Van Baelen, B.; Rosenberg, Z.
Date:
2016-12-01
Abstract:
BACKGROUND
The incidence of human immunodeficiency virus (HIV) infection remains high
among women in sub-Saharan Africa. We evaluated the safety and efficacy of extended
use of a vaginal ring containing dapivirine for the prevention of HIV infection
in 1959 healthy, sexually active women, 18 to 45 years of age, from seven communities
in South Africa and Uganda.
METHODS
In this randomized, double-blind, placebo-controlled, phase 3 trial, we randomly
assigned participants in a 2:1 ratio to receive vaginal rings containing either 25 mg
of dapivirine or placebo. Participants inserted the rings themselves every 4 weeks
for up to 24 months. The primary efficacy end point was the rate of HIV type 1
(HIV-1) seroconversion.
RESULTS
A total of 77 participants in the dapivirine group underwent HIV-1 seroconversion
during 1888 person-years of follow-up (4.1 seroconversions per 100 person-years),
as compared with 56 in the placebo group who underwent HIV-1 seroconversion
during 917 person-years of follow-up (6.1 seroconversions per 100 person-years).
The incidence of HIV-1 infection was 31% lower in the dapivirine group than in
the placebo group (hazard ratio, 0.69; 95% confidence interval [CI], 0.49 to 0.99; P = 0.04). There was no significant difference in efficacy of the dapivirine ring
among women older than 21 years of age (hazard ratio for infection, 0.63; 95% CI,
0.41 to 0.97) and those 21 years of age or younger (hazard ratio, 0.85; 95% CI, 0.45
to 1.60; P = 0.43 for treatment-by-age interaction). Among participants with HIV-1
infection, nonnucleoside reverse-transcriptase inhibitor resistance mutations were
detected in 14 of 77 participants in the dapivirine group (18.2%) and in 9 of 56
(16.1%) in the placebo group. Serious adverse events occurred more often in the
dapivirine group (in 38 participants [2.9%]) than in the placebo group (in 6 [0.9%]).
However, no clear pattern was identified.
CONCLUSIONS
Among women in sub-Saharan Africa, the dapivirine ring was not associated with
any safety concerns and was associated with a rate of acquisition of HIV-1 infection
that was lower than the rate with placebo.
