In the Journals

VOICE trial shows low PrEP adherence, efficacy among women

The final results of the VOICE trial, recently published in the New England Journal of Medicine, show a consistent pattern of nonadherence to pre-exposure prophylaxis among women dating back almost to the beginning of the trial.

“Antiretroviral therapy works for prevention when it’s taken, but significant barriers, including the stigma associated with the disease and these drugs, can compromised its potential,” study researcher Jeanne M. Marrazzo, MD, MPH, professor of medicine at the University of Washington, told Infectious Disease News.

Jeanne M. Marrazzo

VOICE (Vaginal and Oral Interventions to Control the Epidemic) was conducted by the Microbicide Trials Network from 2009 to 2012. It included more than 5,000 women (mean age, 25.3 years) from 15 sites in South Africa, Uganda and Zimbabwe. The randomized, placebo-controlled trial assessed the efficacy of daily use of oral tenofovir disoproxil fumarate (TDF), oral Truvada (tenofovir/emtricitabine, Gilead Sciences; TDF/FTC) and 1% vaginal tenofovir (TFV) gel.

Data from the trial were first presented at CROI 2013.

Low adherence to PrEP

The rate of retention in the study was high (91%), according to the researchers. Based on self-reports and the number of unused products such as gel applicators and leftover pills, PrEP adherence was calculated to be 86% to 90%. However, just 3 months into the trial, less than 40% of women taking some form of TFV-based regimen had detectable levels of the drug in plasma, and most of these women had no detectable TFV at subsequent visits.

In a random sample of women assigned TDF, TDF/FTC, or TFV gel (n=647), TFV was detected in 30%, 29% and 25% of plasma, respectively. Predictors of adherence included being aged older than 25 years (adjusted OR = 1.62; 95% CI, 1.12-2.34), being married (aOR = 2.24; 95% CI, 1.12-4.49) and being multiparous (aOR = 1.84; 95% CI, 1.26-2.69).

A majority of women with no evidence of taking TFV at their first quarterly visit continued with their nonadherence throughout the study, the researchers said.

Efficacy of tenofovir

In a modified intention-to-treat analysis, TFV-based regimens offered low or even no protection against HIV. For example, the effectiveness of TFV gel was 14.5% (HR = 0.85; 95% CI, 0.61-1.21), while the effectiveness of TDF/FTC was –4.4% (HR = 1.04; 95% CI, 0.73-1.49) and TDF, –49% (HR = 1.49; 95% CI, 0.97-2.29).

However, results indicated that patients taking TFV gel whose blood tests did show use of the product at their first visit had a significantly lower likelihood of acquiring HIV (aHR = 0.34; 95% CI, 0.13-0.87). Neither of the other two tenofovir products, when detected in plasma, were associated with a reduced HIV risk.

“Although the numbers are quite small, and there are other inherent limitations with this kind of analysis, we are nonetheless very encouraged to see an association between tenofovir gel use and HIV protection, especially as we await the results of the FACTS 001 study,” Zvavahera Mike Chirenje, MD, of the University of Zimbabwe-University of California San Francisco Collaborative Research Program, said in the release.

The FACTS 001 study is a phase 3 trial of TFV gel used before and after sex. The results of that trial are expected to be presented at CROI 2015.

“We remain committed to finding ways that women can protect themselves against HIV and are hopeful that methods that are less dependent on adherence, such as the monthly dapivirine vaginal ring we are currently evaluating in the ASPIRE study, will help make a difference,” Chirenje added.

In a related editorial, Michael S. Saag, MD, from the Center for AIDS Research at the University of Alabama at Birmingham, noted that the trial results reflect problems of PrEP adherence, not efficacy.

Michael Saag, MD

Michael S. Saag

“At first glance, the VOICE study appears to indicate that pre-exposure prophylaxis doesn’t work in women in Africa and that we should move on to explore other approaches to the prevention of HIV transmission in high-risk settings,” he wrote. “On further review, the study indicates that much more work is needed, not so much in the realm of understanding the biologic basis of pre-exposure prophylaxis as a preventive treatment but rather in the realm of understanding behavioral barriers in the setting of strong social stigma.” – John Schoen

References:

Marrazzo J, et al. #26LB. Pre-exposure prophylaxis for HIV in women: daily oral tenofovir, oral tenofovir/emtricitabine or vaginal tenofovir gel in the VOICE study (MTN 003). Presented at: Conference on Retroviruses and Opportunistic Infections; March 3-6, 2013; Atlanta.

Marrazzo JM, et al. NEJM. 2015;doi:10.1056/NEJMoa1402269.

Saag MS. NEJM. 2015;doi:10.1056/NEJMe1415750.

Disclosure: Marrazzo and Chirenje report no relevant financial disclosures. Please see the full study and commentary for a list of all other authors’ relevant financial disclosures.

The final results of the VOICE trial, recently published in the New England Journal of Medicine, show a consistent pattern of nonadherence to pre-exposure prophylaxis among women dating back almost to the beginning of the trial.

“Antiretroviral therapy works for prevention when it’s taken, but significant barriers, including the stigma associated with the disease and these drugs, can compromised its potential,” study researcher Jeanne M. Marrazzo, MD, MPH, professor of medicine at the University of Washington, told Infectious Disease News.

Jeanne M. Marrazzo

VOICE (Vaginal and Oral Interventions to Control the Epidemic) was conducted by the Microbicide Trials Network from 2009 to 2012. It included more than 5,000 women (mean age, 25.3 years) from 15 sites in South Africa, Uganda and Zimbabwe. The randomized, placebo-controlled trial assessed the efficacy of daily use of oral tenofovir disoproxil fumarate (TDF), oral Truvada (tenofovir/emtricitabine, Gilead Sciences; TDF/FTC) and 1% vaginal tenofovir (TFV) gel.

Data from the trial were first presented at CROI 2013.

Low adherence to PrEP

The rate of retention in the study was high (91%), according to the researchers. Based on self-reports and the number of unused products such as gel applicators and leftover pills, PrEP adherence was calculated to be 86% to 90%. However, just 3 months into the trial, less than 40% of women taking some form of TFV-based regimen had detectable levels of the drug in plasma, and most of these women had no detectable TFV at subsequent visits.

In a random sample of women assigned TDF, TDF/FTC, or TFV gel (n=647), TFV was detected in 30%, 29% and 25% of plasma, respectively. Predictors of adherence included being aged older than 25 years (adjusted OR = 1.62; 95% CI, 1.12-2.34), being married (aOR = 2.24; 95% CI, 1.12-4.49) and being multiparous (aOR = 1.84; 95% CI, 1.26-2.69).

A majority of women with no evidence of taking TFV at their first quarterly visit continued with their nonadherence throughout the study, the researchers said.

Efficacy of tenofovir

In a modified intention-to-treat analysis, TFV-based regimens offered low or even no protection against HIV. For example, the effectiveness of TFV gel was 14.5% (HR = 0.85; 95% CI, 0.61-1.21), while the effectiveness of TDF/FTC was –4.4% (HR = 1.04; 95% CI, 0.73-1.49) and TDF, –49% (HR = 1.49; 95% CI, 0.97-2.29).

However, results indicated that patients taking TFV gel whose blood tests did show use of the product at their first visit had a significantly lower likelihood of acquiring HIV (aHR = 0.34; 95% CI, 0.13-0.87). Neither of the other two tenofovir products, when detected in plasma, were associated with a reduced HIV risk.

“Although the numbers are quite small, and there are other inherent limitations with this kind of analysis, we are nonetheless very encouraged to see an association between tenofovir gel use and HIV protection, especially as we await the results of the FACTS 001 study,” Zvavahera Mike Chirenje, MD, of the University of Zimbabwe-University of California San Francisco Collaborative Research Program, said in the release.

The FACTS 001 study is a phase 3 trial of TFV gel used before and after sex. The results of that trial are expected to be presented at CROI 2015.

“We remain committed to finding ways that women can protect themselves against HIV and are hopeful that methods that are less dependent on adherence, such as the monthly dapivirine vaginal ring we are currently evaluating in the ASPIRE study, will help make a difference,” Chirenje added.

In a related editorial, Michael S. Saag, MD, from the Center for AIDS Research at the University of Alabama at Birmingham, noted that the trial results reflect problems of PrEP adherence, not efficacy.

Michael Saag, MD

Michael S. Saag

“At first glance, the VOICE study appears to indicate that pre-exposure prophylaxis doesn’t work in women in Africa and that we should move on to explore other approaches to the prevention of HIV transmission in high-risk settings,” he wrote. “On further review, the study indicates that much more work is needed, not so much in the realm of understanding the biologic basis of pre-exposure prophylaxis as a preventive treatment but rather in the realm of understanding behavioral barriers in the setting of strong social stigma.” – John Schoen

References:

Marrazzo J, et al. #26LB. Pre-exposure prophylaxis for HIV in women: daily oral tenofovir, oral tenofovir/emtricitabine or vaginal tenofovir gel in the VOICE study (MTN 003). Presented at: Conference on Retroviruses and Opportunistic Infections; March 3-6, 2013; Atlanta.

Marrazzo JM, et al. NEJM. 2015;doi:10.1056/NEJMoa1402269.

Saag MS. NEJM. 2015;doi:10.1056/NEJMe1415750.

Disclosure: Marrazzo and Chirenje report no relevant financial disclosures. Please see the full study and commentary for a list of all other authors’ relevant financial disclosures.