article264

IPrEx

"Preexposure Prophylaxis with FTC-TDF for HIV Prevention in Men".
The New England Journal of Medicine. 2010. 363(27):2587-2599.
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1 Clinical Question
2 Bottom Line
3 Major Points
4 Guidelines
5 Design
6 Population
6.1 Inclusion Criteria
6.2 Exclusion Criteria
6.3 Baseline Characteristics
7 Interventions
8 Outcomes
8.1 Primary Outcome
8.2 Secondary Outcomes
9 Criticisms
10 Funding
11 Further Reading

Clinical Question

Does daily oral FTC-TDF (emtricitabine and tenofovir disoproxil fumarate) reduce the risk of HIV acquisition in men and transgender women who have sex with men?

Bottom Line

Among men and transgender women who have sex with men, daily oral FTC-TDF use resulted in a 44% reduction in HIV acquisition, and detectable blood levels were strongly correlated with the prophylactic effect.

Major Points

The Preexposure Prophylaxis Initiative (iPrEx) trial showed that daily oral FTC-TDF use among men and transgender women who have sex with men correlated with a significant reduction in HIV acquisition. The regimen was more effective when blood levels of the drug were detectable, which highlights the importance of adherence.

Guidelines

As of 2010, preexposure prophylaxis with FTC-TDF was not yet included in guidelines for HIV prevention, awaiting further evidence and regulatory approvals.

Design

- Multicenter, double-blind, randomized, placebo-controlled trial
- N=2499 HIV-seronegative men or transgender women who have sex with men
- FTC-TDF group (n=1248)
- Placebo group (n=1251)
- Setting: 11 sites in six countries
- Enrollment: 2007-2009
- Follow-up: Median 1.2 years (maximum 2.8 years)
- Analysis: Modified intention-to-treat
- Primary outcome: HIV acquisition

Population

Inclusion Criteria:
- Male sex at birth, age of 18 years or older, HIV-seronegative status, and evidence of high risk for acquisition of HIV infection

Exclusion Criteria:
- Information not provided

Baseline Characteristics
- All subjects were born male, although 1% reported their current gender identity as female
- Mean age ranged from 26.8 to 27.5 years; the FTC-TDF group was on average nine months older than the placebo group

Interventions

- Administration of daily oral FTC-TDF or placebo
- Subjects also received HIV testing, risk-reduction counseling, condoms, and management of sexually transmitted infections

Outcomes

Primary Outcome:
- 36 HIV acquisitions in the FTC-TDF group compared to 64 in the placebo group, representing a 44% reduction in HIV incidence (95% CI, 15 to 63; P=0.005)

Secondary Outcomes:
- Rates of serious adverse events similar in both groups (P=0.57)
- Nausea reported more frequently during the first 4 weeks in the FTC-TDF group (P<0.001)
- Similar rates of elevation in serum creatinine in both groups, though more creatinine elevations trended in the FTC-TDF group

Criticisms

- The protective effect of FTC-TDF did not meet the initially hypothesized efficacy rate
- Drug-level detection was low among users, potentially impacting the study's conclusions about drug efficacy and adherence

Funding

- Division of Acquired Immunodeficiency Syndrome (DAIDS), National Institute of Allergy and Infectious Diseases, Bill and Melinda Gates Foundation. Study drugs were donated by Gilead Sciences