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What do we know about PrEP effectiveness in women?
Oral pre-exposure prophylaxis (PrEP) has demonstrated high levels of effectiveness in research conducted among gay men and other men who have sex with men (MSM);1however, research in women has shown mixed results,2,3,4,5,6 leading to concerns that PrEP may be less effective for women. Of the five randomized controlled trials (RCTs) that included women, 2,3,4,5,6 two trials (in women alone) found that a daily oral PrEP regimen was not effective at reducing the risk of HIV transmission.2,3 Very low levels of adherence to daily PrEP (less than 30%) among women in these two studies is likely responsible for the lack of effectiveness observed. However, other trials5,6 have shown that, with good adherence, PrEP is effective at reducing the risk for HIV transmission in women.
Biological differences in the way that PrEP accumulates in the body may be partly responsible for the mixed results observed in women. Pharmacokinetic evidence shows that PrEP concentrations are lower in the vagina (compared to the rectum), meaning that high adherence to daily PrEP may be especially important for women exposed to HIV through vaginal sex.7,8
Meta-analysis looks at adherence and effectiveness in women
A new meta-analysis used data from the five RCTs conducted in women to estimate the effectiveness of daily oral PrEP in women with varying levels of adherence.9 These five studies were conducted in different populations of women:
Two studies enrolled individual African women at risk of HIV through sexual exposure2,3
Two studies enrolled African women and men at risk of HIV through sexual exposure (one enrolled individuals4 and the other enrolled heterosexual serodiscordant couples)5
One study enrolled individual women and men in Thailand who inject drugs and may be at risk of HIV through sex and/or sharing needles and other injection drug-use equipment6
While PrEP is currently available as a two-drug combination (TDF and FTC) under the brand name Truvada, some participants in these studies were taking the two-drug combination and some were taking a version of PrEP containing TDF alone. In these studies, the two-drug formulation of PrEP was more effective at preventing HIV transmission when compared to TDF alone;2,5 however, participants taking both versions of PrEP were included in this analysis.
This study found a strong relationship between adherence to PrEP and effectiveness. A combined analysis of the results from all five studies estimated that PrEP reduced the risk of HIV infection by:
36% among all women who participated in these studies (note that this estimate reflects a wide range of adherence levels, including many women who were not adherent at all to PrEP), and
61% among women with 75% adherence to PrEP, based on PrEP levels detected in the blood.
What does this mean for Canadian service providers?
Evidence from multiple studies in different populations tells us that PrEP effectiveness increases with higher adherence to the medication as prescribed.1,2,3,4,5,6 This meta-analysis demonstrates that 75% adherence to daily PrEP may not be enough for women to obtain the high levels of effectiveness seen in MSM with moderate-to-high adherence. For example, the iPrEX trial found that MSM who had any PrEP detected in their blood (and were not necessarily highly adherent) had a 92% reduced risk of HIV transmission compared to those without PrEP in the blood.1
This meta-analysis does not provide an estimate for women with optimal adherence to daily PrEP. An adherence-based analysis from the Partners PrEP study of heterosexual serodiscordant couples found that women who were highly adherent to PrEP had high levels of protection.10 The Partners PrEP analysis found a 92% reduced risk of HIV infection among women who had PrEP (TDF/FTC) blood-levels consistent with daily dosing.10
Overall low adherence among women in two trials likely contributed to the relatively low effectiveness estimate in this meta-analysis. Research has identified that women in these studies were not taking the PrEP medications given to them for many reasons, such as stigma, mistrust of the research and fear of side-effects.11 Although these may not apply for women in the current Canadian context, it will be necessary for service providers to stress the importance of adherence for women taking PrEP. It is important for service providers to discuss and assess adherence in all clients taking PrEP and provide adherence counselling if necessary.
1.a. b. c. Grant RM, Lama JR, Anderson PL, et al. Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men. New England Journal of Medicine. 2010 Dec 30;363(27):2587–99.
2.a. b. c. d. e. f. Marrazzo JM, Ramjee G, Richardson BA, et al. Tenofovir-Based Preexposure Prophylaxis for HIV Infection among African Women. New England Journal of Medicine. 2015 Feb 5;372(6):509–18.
3.a. b. c. d. e. Van Damme L, Corneli A, Ahmed K, et al. Preexposure prophylaxis for HIV infection among African women. New England Journal of Medicine. 2012 Aug 2;367(5):411–22.
4.a. b. c. Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. New England Journal of Medicine. 2012 Aug 2;367(5):423–34.
5.a. b. c. d. e. f. Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. New England Journal of Medicine. 2012 Aug 2;367(5):399–410.
6.a. b. c. d. e. Choopanya K, Martin M, Suntharasamai P, et al. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, double-blind, placebo-controlled phase 3 trial. The Lancet. 2013 Jun;381(9883):2083–90.
7.Cottrell ML, Srinivas N, Kashuba AD. Pharmacokinetics of antiretrovirals in mucosal tissue. Expert Opinion on Drug Metabolism and Toxicology. 2015; 11: 893–905.
8.Cottrell ML, Yang KH, Prince H, et al. A translational pharmacology approach to predicting HIV pre-exposure prophylaxis outcomes in men and women using tenofovir disproxil fumarate + emtricitabine. Journal of Infectious Diseases. 2016; in press.
- 9.Hanscom B, Janes HE, Guarino PD et al. Brief report: Preventing HIV-1 infection in women using oral preexposure prophylaxis: A meta-analysis of current evidence. Journal of Acquired Immune Deficiency Syndromes. 2016 Dec 15;73(5):606-608.
- 10.a. b. Donnell D, Baeten JM, Bumpus NN, et al. HIV protective efficacy and correlates of tenofovir blood concentrations in a clinical trial of PrEP for HIV prevention. Journal of Acquired Immune Deficiency Syndromes. 2014 Jul 1;66(3):340-48.
11.Corneli A, McKenna K, Perry B, et al. The science of being a study participant: FEM-PrEP participants’ explanations for overreporting adherence to the study pills and for the whereabouts of unused pills. Journal of Acquired Immune Deficiency Syndromes. 2015 Apr 15;68(5):578-84.
About the author: Camille Arkell is CATIE’s Knowledge Specialist, Biomedical Science of Prevention. She has a Master’s of Public Health degree in Health Promotion from the University of Toronto, and has been working in HIV education and research since 2010.
This article by Camille Arkell previously appeared at CATIE, here.
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