Ellie Kamarjian, PharmD Candidate 2015 Mercer University College of Pharmacy
Pre-exposure prophylaxis is a prevention option for people who are at high risk of getting human immunodeficiency virus (HIV). The Centers for Disease Control and Prevention (CDC) recommends taking Truvada® (tenofovir and emtricitabine) daily as a pre-exposure prophylaxis. Truvada® reduced the risk of getting HIV infection by up to 92% for those who took the medicines consistently than for those who didn’t.1
|Title: Tenofovir-Based Pre-exposure Prophylaxis for HIV Infection among African Women|
|Design||Randomized, placebo-controlled trial|
|Objective||To assess daily treatment with tenofovir-based pre-exposure prophylaxis against HIV type 1 (HIV-1) infection in women in South Africa, Uganda, and Zimbabwe|
|Study Groups||Five study groups: Oral tenofovir disoproxil fumarate (TDF) 300 mg with a TDF-FTC placebo, oral tenofovir-emtricitabine (TDF-FTC) 300 mg of TDF and 200 mg of FTC) with TDF placebo, both TDF-FTC placebo and TDF placebo, one percent tenofovir (TFV) vaginal gel, or vaginal placebo gel|
|Methods||Participants (N = 5029) were randomly assigned in a 1:1:1:1:1 to one of the five regimens. Patients were counseled to use products daily. HIV-1 testing was performed monthly, and plasma TFV levels were assessed quarterly. Patients were followed for eight weeks after the last visit.|
|Duration||September 2009 through August 2012|
|Primary Outcome Measure||HIV-1 Infection identified by seroconversion|
|Baseline Characteristics||Mean age was 25.3 years, 21% of women were married, and 71% were using injectable hormonal contraception with a reported mean of 2.5 episodes of vaginal intercourse during the seven days before enrollment|
|Results||A total of 312 HIV-1 infections occurred; the incidence of HIV-1 infection was 5.7 per 100 person-years. The incidence was highest among participants who were younger than 25 years of age and among those who were unmarried. Fifty-two occurred in the TDF group, 61 in the oral placebo group, and 70 in the placebo gel group. In the modified intention-to-treat analysis, the effectiveness was -49.0% with TDF (hazard ratio for infection, 1.49; 95% confidence interval [CI], 0.97 to 2.29), -4.4% with TDF-FTC (hazard ratio, 1.04; 95% CI, 0.73 to 1.49), and 14.5% with TFV gel (hazard ratio, 0.85; 95%CI, 0.61 to 1.21). In a random sample, TFV was detected in 30%, 29%, and 25% of available plasma samples from participants randomly assigned to receive TDF, TDF-FTC, and TFV gel, respectively.|
|Adverse Events||Common Adverse Events: Elevated serum creatinine levels were seen more frequently among participants randomly assigned to the oral TDF-FTC group than among those in the oral placebo group (1.3% vs. 0.2%, p = 0.004); all but one of these elevations were mild|
|Serious Adverse Events: None reported|
|Percentage that Discontinued due to Adverse Events: None reported|
|Study Author Conclusions||None of the drug regimens evaluated reduced the rates of HIV-1 acquisition in an intention-to-treat analysis. The adherence to study drugs was low.|
Despite having adequate access to therapy, counseling, and treatments, adherence was very low for patients in this trial. Since the use of medication therapy for the pre-exposure prophylaxis of HIV infection relies heavily on patient compliance, this study was unable to show that therapy with tenofovir was beneficial. Ultimately, until adherence can be improved, pre-exposure benefits are improbable.
- HIV Basics. Centers for Disease Control and Prevention website. Available at: http://www.cdc.gov/hiv/basics/prep.html. Accessed February 10, 2015.
- Marrazzo JM, Ramjee G, Richardson BA, et al. Tenofovir-based preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2015; 372(6)509-518.