Antiretroviral gels: facing the FACTS
2015; Elsevier BV; Volume: 2; Issue: 4 Linguagem: Inglês
10.1016/s2352-3018(15)00046-6
ISSN2405-4704
Autores Tópico(s)HIV, Drug Use, Sexual Risk
ResumoPrevention was one of the big topics at the recent Conference on Retroviruses and Opportunistic Infections in Seattle (WA, USA, Feb 23–26). There was good news about pre-exposure prophylaxis (PrEP) for men who have sex with men (MSM)—results from the PROUD and IPERGAY studies showed that tenofovir with emtricitabine, taken either daily or on demand around sexual encounters, can emphatically reduce the risk of HIV. These findings corroborate previous studies, including iPrEx, which have led to the use of PrEP among MSM in the USA. The new findings must surely lead to more widespread licensing of this preventive strategy, which will give this key population more control over their risk of HIV. However, the news was not so good for one prevention strategy for women that had shown promise in earlier stages of development.There were high hopes that the eagerly awaited results of the FACTS 001 trial would breathe life back into the prospect of vaginal tenofovir gel for prevention of HIV acquisition, but when the results were presented—an incidence rate ratio of 1 for HIV acquisition in the tenofovir gel group relative to the placebo group—the defeated sigh from the gathered audience was clearly audible (probably in the next room). Back in 2010, the presentation of results of the CAPRISA 004 study had a celebratory reception at the International AIDS Society meeting in Vienna, Austria. That study in almost 900 women in South Africa showed an incidence rate ratio of 0·61 for women who applied vaginal tenofovir gel before and after sex relative to those who used placebo gel. The results created much expectation that gels would revolutionise prevention, empowering women to take risk management into their own hands.However, in 2012 results of the FEM-PrEP study in over 2000 women in Kenya, South Africa, and Tanzania showed no benefit to using the gel (hazard ratio 0·94 relative to placebo). The VOICE study in over 5000 women in South Africa, Uganda, and Zimbabwe followed suit: the final results published in early February, 2015, showed not only no significant difference between the gel and placebo groups, but also no effect for oral PrEP regimens of either tenofovir or tenofovir with emtricitabine given daily. The negative result of the FACTS 001 study in over 2000 women in South Africa seems a little like the final nail in the coffin for antiretroviral gels for the prevention of HIV in women.A recurring feature of the negative trials is the apparent poor adherence to the prevention interventions. Pharmacokinetic studies show that only a small proportion of the participants achieved drug concentrations that would have been able to prevent infection. In participants achieving the required drug concentrations, gel does seem to be effective, explaining the early positive results of the CAPRISA study. The FACTS investigators suggest also that the situations of the women enrolled in the study prevented them from using the gel effectively—many of the women lived at home with their parents and so left their house to have sex, diminishing their ability to have sex on their own terms and to use the gel. The fact that time and again study participants have not been able to use the intervention as required to have an effect suggests that although the intervention might be biologically plausible it is not practically feasible for the people who need it.The finding of the VOICE trial that oral regimens are also unable to be adhered is a further blow to HIV prevention strategies for women. As the options improve for MSM, doors seem to be closing for women. Although much of the focus in recent years has been on key populations such as MSM and injecting drug users, in the region with the greatest burden of HIV, women are the key population—60% of people living with HIV in sub-Saharan Africa are women.The next great hope for HIV prevention strategies for use by women are antiretroviral microbicide rings— dapivirine impregnated devices worn inside the vagina that its hoped will provide protection from HIV for 1 month or more. Two trials, The Ring Study and ASPIRE are expected to be reported in 2016. The studies have included over 4500 women in sub-Saharan Africa, and together with a few smaller studies in Europe and the USA could provide sufficient support for licensure if shown to prevent HIV. Effective and usable prevention strategies for women are urgently needed to combat the generalised epidemic in sub-Saharan Africa and to give women more options to manage their risk of HIV worldwide. Increasingly it looks like gels will not meet that need.For more on antiretroviral microbicide rings see http://www.ipmglobal.org/node/532 Prevention was one of the big topics at the recent Conference on Retroviruses and Opportunistic Infections in Seattle (WA, USA, Feb 23–26). There was good news about pre-exposure prophylaxis (PrEP) for men who have sex with men (MSM)—results from the PROUD and IPERGAY studies showed that tenofovir with emtricitabine, taken either daily or on demand around sexual encounters, can emphatically reduce the risk of HIV. These findings corroborate previous studies, including iPrEx, which have led to the use of PrEP among MSM in the USA. The new findings must surely lead to more widespread licensing of this preventive strategy, which will give this key population more control over their risk of HIV. However, the news was not so good for one prevention strategy for women that had shown promise in earlier stages of development. There were high hopes that the eagerly awaited results of the FACTS 001 trial would breathe life back into the prospect of vaginal tenofovir gel for prevention of HIV acquisition, but when the results were presented—an incidence rate ratio of 1 for HIV acquisition in the tenofovir gel group relative to the placebo group—the defeated sigh from the gathered audience was clearly audible (probably in the next room). Back in 2010, the presentation of results of the CAPRISA 004 study had a celebratory reception at the International AIDS Society meeting in Vienna, Austria. That study in almost 900 women in South Africa showed an incidence rate ratio of 0·61 for women who applied vaginal tenofovir gel before and after sex relative to those who used placebo gel. The results created much expectation that gels would revolutionise prevention, empowering women to take risk management into their own hands. However, in 2012 results of the FEM-PrEP study in over 2000 women in Kenya, South Africa, and Tanzania showed no benefit to using the gel (hazard ratio 0·94 relative to placebo). The VOICE study in over 5000 women in South Africa, Uganda, and Zimbabwe followed suit: the final results published in early February, 2015, showed not only no significant difference between the gel and placebo groups, but also no effect for oral PrEP regimens of either tenofovir or tenofovir with emtricitabine given daily. The negative result of the FACTS 001 study in over 2000 women in South Africa seems a little like the final nail in the coffin for antiretroviral gels for the prevention of HIV in women. A recurring feature of the negative trials is the apparent poor adherence to the prevention interventions. Pharmacokinetic studies show that only a small proportion of the participants achieved drug concentrations that would have been able to prevent infection. In participants achieving the required drug concentrations, gel does seem to be effective, explaining the early positive results of the CAPRISA study. The FACTS investigators suggest also that the situations of the women enrolled in the study prevented them from using the gel effectively—many of the women lived at home with their parents and so left their house to have sex, diminishing their ability to have sex on their own terms and to use the gel. The fact that time and again study participants have not been able to use the intervention as required to have an effect suggests that although the intervention might be biologically plausible it is not practically feasible for the people who need it. The finding of the VOICE trial that oral regimens are also unable to be adhered is a further blow to HIV prevention strategies for women. As the options improve for MSM, doors seem to be closing for women. Although much of the focus in recent years has been on key populations such as MSM and injecting drug users, in the region with the greatest burden of HIV, women are the key population—60% of people living with HIV in sub-Saharan Africa are women. The next great hope for HIV prevention strategies for use by women are antiretroviral microbicide rings— dapivirine impregnated devices worn inside the vagina that its hoped will provide protection from HIV for 1 month or more. Two trials, The Ring Study and ASPIRE are expected to be reported in 2016. The studies have included over 4500 women in sub-Saharan Africa, and together with a few smaller studies in Europe and the USA could provide sufficient support for licensure if shown to prevent HIV. Effective and usable prevention strategies for women are urgently needed to combat the generalised epidemic in sub-Saharan Africa and to give women more options to manage their risk of HIV worldwide. Increasingly it looks like gels will not meet that need. For more on antiretroviral microbicide rings see http://www.ipmglobal.org/node/532 For more on antiretroviral microbicide rings see http://www.ipmglobal.org/node/532 For more on antiretroviral microbicide rings see http://www.ipmglobal.org/node/532 The FACTS about women and pre-exposure prophylaxisThe Editorial in the April issue, Antiretroival gels: facing the FACTS, describes the HIV community's collective disappointment regarding the FACTS trial's negative results.1 However, the conclusions that gels are not “practically feasible” and vaginal rings may be the “usable prevention strategy” that women need is misguided. Oral pre-exposure prophylaxis (PrEP) is more promising than ever for women: the HPTN 067 ADAPT trial and Partners PrEP Demonstration Project, both presented at the same conference as FACTS, confirmed that women want HIV prevention methods and adhere to daily oral dosing, especially when open-label products known to be effective are used. Full-Text PDF
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