Use of a Vaginal Ring Containing Dapivirine for HIV-1 Prevention in Women

Le Trac, Mercer University College of Pharmacy

According to the World Health Organization (WHO), sub-Saharan Africa is the region that has the most incidences of human immunodeficiency virus type 1 (HIV-1) infection in the world. In 2011, there was an estimate of 25.8 million people living with HIV in this region, representing 70% of the global HIV burden. [1]

Dapivirine is an investigational drug that is not yet approved by the Food and Drug Administration (FDA) for sale in the United States. It is a non-nucleoside HIV-1 reverse transcriptase inhibitor. It is stated that women using the dapivirine vaginal ring were less susceptible to HIV-1 when challenged ex vivo. [2]

Title: Use of a Vaginal Ring Containing Dapivirine for HIV-1 Prevention in Women [3]
Design Phase 3, randomized, double-blind, placebo-controlled; N= 168
Objective To determine the efficacy and safety of the dapivirine vaginal ring as compared with a placebo ring
Study Groups Dapivirine group (n= 1,313); placebo group (n= 1,316)
Methods Women between the ages of 18 and 45 years in Malawi, South Africa, Uganda, and Zimbabwe enrolled in the study to receive either a silicone elastomer vaginal matrix ring containing 25 mg of dapivirine or a placebo vaginal ring. At monthly follow-up visits, a new ring was provided and the used ring was collected. The detection of a plasma dapivirine level of > 95 pg/mL was used to define adherence.
Duration August 2012 to June 2015
Primary Outcome Measure HIV-1 infection, identified with the use of a standard seroconversion algorithm
Baseline Characteristics
Characteristic Dapivirine group (n= 1,313) (%) Placebo group (n= 1,316) (%)
Mean age 27.2 +/- 6.1 27.3 +/- 6.3
Secondary school education or higher 84 85
Earns own income 46 44
Currently married 40 42
Two or more male sex partners in the past 3 months 16 17
Condom use during last vaginal sex 59 56
Sexually transmitted infection
Chlamydia trachomatis 13 11
Neisseria gonorrhoeae 4 4
Trichomonas vaginalis 7 7
Results Results for overall 15-site analysis:

Group HIV-1 incidence per 100 person-years 95% confidence interval (CI)
Dapivirine 3.3 2.6-4.2
Placebo 4.5 3.7-5.5

 

Results after the exclusion of data from two sites because of lower-than-expected protocol and product adherence:

Group HIV-1 incidence per 100 person-years 95% CI
Dapivirine 2.8 2.1-3.6
Placebo 4.4 3.5-5.5

 

Cumulative incidence of HIV-infection according to age group:

Age HIV incidence in dipivirine group (no. of participants/no. of HIV-1 infections) HIV incidence in placebo group (per 100 person-years) 95% CI
18 to 21 years 451/44 5.4 3.2-8.4
22 to 26 years 752/51 6.1 4.3-8.3
27 to 45 years 1192/44 3.0 2.0-4.4
Adverse Events Common Adverse Events (occurred in < 0.5% of the population, actual percentages not provided): menorrhagia, vulvovaginal candidiasis, menometrorrhagia, bacterial vaginosis, vaginal discharge, and cervical dysplasia
Serious Adverse Events: N/A
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions A monthly vaginal ring containing dapivirine reduced the risk of HIV-1 infection among African women, with increased efficacy in subgroups with evidence of increased adherence.

It was shown that dapivirine vaginal ring provides some protection against HIV-1 acquisition. Although the monthly vaginal ring was thought to increase adherence, thus improving HIV-1 protection, results still show a low efficacy of the drug in younger age groups. This may be due to the fact that subjects were categorized as being adherent even when they only used the ring for a portion of a month, which means that there could have been an overestimation of adherence rates. Education about adherence would be imperative before prescribing this medication to young women.

 

References

  1. HIV/AIDS. World health Organization. 2015. Available at http://www.who.int/mediacentre/factsheets/fs360/en/. Accessed February 23, 2016.
  2. AIDSinfo database. 2015. Available at https://aidsinfo.nih.gov/drugs/523/dapivirine/0/patient. Accessed February 23, 2016.
  3. Baeten JM, Palanee-Philips T, Brown ER, et al. Use of a Vaginal Ring Containing Dapivirine for HIV-1 Prevention in Women. N Eng J Med. 2016. DOI: 10.1056/NEJMoa1506110.
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