Raltegravir‐emtricitabine‐tenofovir as HIV nonoccupational post‐exposure prophylaxis in men who have sex with men: safety, tolerability and adherence

Abstract

ObjectivesThree-drug nonoccupational post-exposure prophylaxis (NPEP) typically includes co-formulated emtricitabine-tenofovir (FTC-TDF) and a protease inhibitor. However, protease inhibitors can cause significant toxicities, can interact with prescribed and illicit drugs, and work late in the viral cycle. Agents that act before viral integration into host DNA may have efficacy advantages. Raltegravir (RAL) is a good candidate for NPEP as it has few side effects or drug interactions and acts prior to HIV integration. The objective of this study was to investigate the use of RAL in 3-drug NPEP in terms of safety, adherence and tolerability. MethodsWe evaluated 28 days of RAL-FTC-TDF treatment in 86 men and FTC-TDF treatment in 34 men eligible for three-and two-drug NPEP, respectively. We assessed adherence (compared between groups and with nonstudy controls) and clinical and adverse events at weeks 1, 2 and 4, and efficacy at week 12. Analyses were by intention to treat, excluding from the adherence analysis subjects who ceased NPEP because their source was HIV-uninfected. ResultsNo participant became infected with HIV. For RAL-FTC-TDF and FTC-TDF, regimen completion rates were 92% and 91% and medication adherence rates were 89% and 90%, respectively. Eight (9%) RAL recipients developed mild myalgias, with four developing transient grade 4 elevations in creatine kinase (two developed both), all of which improved to grade 2 or less by week 4 without RAL discontinuation. Eight prescribed and 37 potential illicit drug interactions with a protease inhibitor were avoided by use of RAL. ConclusionsRAL-FTC-TDF is well tolerated as NPEP, results in high levels of adherence and avoids potential drug−drug interactions. Patients and clinicians should be aware of the potential for acute muscle toxicity when RAL is used as NPEP. ORIGINAL RESEARCH13 randomized study of ART as pre-exposure prophylaxis in men who have sex with men (MSM); and a randomized trial of ART as prevention in HIV-serodiscordant, heterosexual couples [5][6][7][8][9]. PEP does not always prevent HIV transmission [10][11][12]. Longer time to first PEP dose, incomplete PEP adherence, continued HIV risk behaviour and primary ART drug resistance have each been linked to failure [11,12]. In seven PEP studies published since 2001, 51% of the total 1009 participants reported at least one adverse event (AE) and around 20% failed to complete the 28-day course [13][14][15][16][17][18][19].The use of three antiretroviral agents in PEP is common [1-4] but based solely on standard-of-care treatment of HIV infection. The most commonly used third drug is a protease inhibitor [1][2][3][4]. Protease inhibitors prevent mature HIV protein formation within cells in which HIV is already integrated into host-cell DNA. Agents that act before viral integration may have efficacy advantages by preventing rather than limiting infection. In addition, some prescribed and proscribed drugs have potentially dangerous interactions with protease inhibitors.Raltegravir (RAL) is an HIV inte...

Longitudinal Trends in HIV Nonoccupational Postexposure Prophylaxis Use at a Boston Community Health Center Between 1997 and 2013

“…14-19 In addition, subsequent HIV acquisition rates have been high among MSM PEP users in several series. 15,20-23 Multiple centers have reported that newer PEP regimens have improved tolerability and fewer drug-drug interactions 24-28 compared to earlier regimens. 29-31 However, the factors associated with NPEP completion and non-completion have not been well-described, as few studies have examined long-term trends of NPEP use within the past 10 years.…”

Current perspectives in HIV post-exposure prophylaxis

“…A recent PEP study found that almost half of the participants were regularly taking at least one prescribed medication. These included corticosteroids, anticonvulsants, antidepressants, anti-lipids, and antihypertensives, which are known to have potential drug interactions with PIs 75. It is important to consider drug–drug interactions with prescribed and nonprescribed drugs, including recreational drugs when selecting the best PEP regimen.…”

“…Raltegravir (RAL), an INI, has a favorable tolerability, safety, and metabolic profile,76 and is well-tolerated as PEP 75,77. It acts before viral integration and thus may be more effective at preventing HIV infection.…”

“…The New York State Department of Health recently started using RAL, FTC, TDF as its first-line occupational and nonoccupational PEP regimen, and the Center for Disease Control (CDC) now recommends the use of RAL for occupational PEP 78. A recent interventional study assessed RAL as part of a triple drug PEP regimen, including FTC and TDF, in comparison to FTC and TDF 75. Researchers found the RAL regimen had a high completion rate, was effective, and avoided potential drug–drug interactions.…”

Sexual Assault and Sexually Transmitted Infections in Adults, Adolescents, and Children

“…Since 2013, the preferred regimen for nPEP in the United States now consists of a 3-drug regimen (ie, tenofoviremtricitabine and raltegravir) that has been shown to be well tolerated and to have high levels of adherence among men who have sex with men (MSM) [27,28]. Recent CDC guidelines have also been issued regarding the use of preexposure prophylaxis (PrEP) for HIV prevention [35].…”