CATIE News

1 December 2011 

Confusion over contradictory PrEP results

Pre-exposure prophylaxis

Pre-exposure prophylaxis, or PrEP, is currently being studied as a potential method for a person who is at risk of HIV infection to reduce their risk of becoming infected. It involves taking anti-HIV medications on a regular basis.

There are several types of PrEP being investigated. PrEP drugs may be available in a variety of forms, including pills taken orally (also known as oral PrEP) or gels inserted into the vagina or rectum (also known as topical PrEP or antiretroviral-based microbicides). The drugs may need to be taken every day, or before and after sex, or intermittently (once or twice a week).

Topical and oral forms of PrEP continue to be studied so that researchers can be certain about their effectiveness. Most types of PrEP being studied use the antiretroviral drug tenofovir (called Viread when used in pill form) or combinations of tenofovir and FTC (sold as a fixed-dose co-formulation pill called Truvada).

However, while some PrEP clinical trials have had promising results, others have not.

Promising PrEP results

The first promising PrEP result came from the CAPRISA study. The researchers found that HIV-negative women who applied a gel containing tenofovir into the vagina before and after sex reduced their risk of infection by 39%. Women who applied the gel more consistently reduced their risk of infection by as much as 54%.

Some studies of oral PrEP have also produced promising results. A study called iPrEx found that HIV-negative gay and bisexual men who took a Truvada pill daily reduced their risk of HIV infection by 44%. Men who took the pill more consistently reduced their risk by as much as 73%. In two other studies among heterosexual men and women, a Viread or Truvada pill taken daily provided similar levels of protection.

Contradictory PrEP results

Surprisingly, some of the same types of PrEP that were found to be effective in the clinical trials mentioned above were not found to be effective in other studies:

  • In April of this year, a study called FEM-PrEP was stopped early because it seemed that a daily Truvada pill was not able to reduce the risk of HIV infection among heterosexual women.
  • More recently, two types of PrEP being investigated in a study called VOICE were also found to be ineffective at preventing HIV infection for women enrolled in the trial.

These contradictory results have caused concern about whether PrEP will work for women and other populations.

The VOICE study

The VOICE (Vaginal and Oral Interventions to Control the Epidemic) study was designed so that researchers could compare the effectiveness and safety of different types of PrEP in preventing HIV infection in women.

More than 5,000 women from Eastern and Southern Africa were enrolled in the study. Researchers randomly assigned the women to one of five study arms. Each group was asked to use or take one of the following on a daily basis:

  • tenofovir vaginal gel
  • placebo vaginal gel
  • tenofovir (Viread) pill
  • Truvada pill
  • placebo pill

The VOICE study was one of the only ongoing studies investigating the same gel that was found to be effective when used before and after sex by women in the CAPRISA study. However, unlike the CAPRISA study, the VOICE study was looking at the effectiveness of this gel when used daily.

Two arms of VOICE study stopped early

Many trials have an independent oversight committee called a Data and Safety Monitoring Board (DSMB). The role of a DSMB is to periodically review the data collected from a study and to stop or modify the study if there are concerns about the safety of participants or the effectiveness of interventions being studied.

In October, the DSMB recommended that women enrolled in the VOICE study who were receiving tenofovir pills stop taking them because they were not found to be effective in reducing the risk of HIV infection.

More recently, at the end of November, the DSMB also recommended that women in VOICE stop using the daily tenofovir vaginal gel for the same reason. This was surprising because the same gel was able to reduce the risk of HIV infection in the CAPRISA study when used before and after sex. These study arms were not stopped because of safety concerns.

The arm of the study investigating the effectiveness of taking a daily Truvada pill is continuing.

What’s next for oral and topical PrEP for women?

The reason(s) for the contradictory results of these studies of oral and topical PrEP for women are not yet known. An in-depth analysis of the FEM-PrEP and VOICE results are expected within the next few months. This analysis will hopefully be able to answer some of the questions raised by these studies.

The lack of effectiveness of the vaginal gel used in the VOICE study deals a large blow to the hope that there will be a safe and effective microbicide available in the near future. After the release of the results from the CAPRISA study, there was a general consensus that confirmatory results were needed before the gel could be made available. It was hoped that the results from the VOICE study would provide the additional evidence needed for regulatory approval of the gel.

Only two large PrEP studies are currently ongoing. One study is looking at the effectiveness of a daily tenofovir pill when used by people who use injection drugs. Another study called FACTS 001 is investigating the same regimen used in the CAPRISA study, a tenofovir vaginal gel used before and after sex. However, the FACTS 001 study has just begun to enroll participants and is not expected to be completed until 2013.

Currently, PrEP remains unapproved by regulatory agencies in Canada, the United States and elsewhere. Until more is known, it is unlikely that PrEP will be approved for women due to these recent contradictory findings. These results may also delay PrEP approval for gay and bisexual men.

                                                                                                            —James Wilton

Resources:

CATIE-News story on VOICE study
CATIE Prevention in Focus article on PrEP
CATIE Fact Sheet on PrEP
CATIE-News story on iPrEx trial
CATIE-News story on FEM-PrEP trial
CATIE-News story on TDF2 and Partners PrEP

REFERENCES:

  1. Abdool Karim Q, Abdool Karim SS, Frohlich JA, et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science. 2010 Sep 3;329(5996):1168-74. 
  2. Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010 Dec 30;363(27):2587–99.
  3. Baeten J. Antiretroviral pre-exposure prophylaxis for HIV-1 prevention among heterosexual African men and women: the Partners PrEP study. In: Program and abstracts of the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, 17-20 July 2011, Rome. Abstract MOAX0106.
  4. Thigpen M, Kebaabetswe PM, Smith DK, et al. Daily oral antiretroviral use for the prevention of HIV infection in heterosexually active young adults in Botswana: results from the TDF2 Study. In: Program and abstracts of the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, 17-20 July 2011, Rome. Abstract WELBC01.
  5. Family Health International. FHI to initiate orderly closure of FEM-PrEP. Press release. 18 April 2011.
  6. Microbicide Trials Network. MTN statement on decision to discontinue use of oral tenofovir tablets in VOICE, a major HIV prevention study in women. Press release. 28 September 2011.
  7. Microbicide Trials Network. MTN statement on decision to discontinue use of tenofovir gel in VOICE, a major HIV prevention study in women. Press release. 25 November 2011.