快樂小藥師 Im pharmacist nichts glücklich

Question:

I have started receiving prescriptions for tenofovir disoproxil fumarate/emtricitabine (Truvada®) for preexposure prophylaxis against HIV infection. What specific considerations or guidance are available to safely evaluate and monitor these patients?

Response from Kim Scarsi, MS, PharmD
Research Assistant Professor, Northwestern University Feinberg School of Medicine, Chicago, Illinois

About 48,100 new HIV infections occur annually in the United States, 61% of which occur in men who have sex with men (MSM).[1] Antiretroviral preexposure prophylaxis (PrEP) is an exciting new tool for HIV prevention and is currently under investigation in various high-risk groups. One PrEP strategy includes tenofovir disoproxil fumarate/emtricitabine (TDF/FTC; marketed as Truvada®), a combination tablet including 2 nucleoside reverse transcriptase inhibitor antiretroviral agents.

Although TDF/FTC is not yet approved by the US Food and Drug Administration for this indication, the Centers for Disease Control and Prevention (CDC) issued specific guidance on the use of TDF/FTC in MSM for PrEP.[2] These guidelines followed the publication of the iPrEx study, an evaluation of TDF/FTC vs placebo in 2499 HIV-negative MSM, which found that TDF/FTC reduced the risk for new HIV infections by 44% (95% confidence interval, 15 %-63%; P = .005).[3]

On the basis of the CDC interim guidelines,[2] patients are eligible to receive PrEP with TDF/FTC, 300/ 200 mg once daily, if they are MSM who are at high risk for acquiring HIV infection and are confirmed to be HIV-negative before PrEP. Guidance from the CDC includes, but is not limited to, the following recommendations[2]:

Laboratory monitoring before and during PrEP. Pretreatment calculated creatinine clearance of 60 mL/min/1.73 m2 or greater should be confirmed before initiation of PrEP. Follow-up renal function monitoring is recommended 3 months after starting TDF/FTC prophylaxis and then yearly thereafter. This is important because both TDF and FTC are renally eliminated, and renal impairment is an adverse effect associated with TDF.
Hepatitis B screening and vaccination. Patients should be screened and vaccinated against hepatitis B if they are susceptible. TDF/FTC is active against both HIV and hepatitis B virus. Specific considerations apply to patients who are co-infected with hepatitis B virus (refer to the CDC guidance).[2]
Prescription amount of TDF/FTC. Patients should be prescribed no more than a 90-day supply of medication, with refills only after the patient receives follow-up HIV testing (recommended every 2-3 months during PrEP). This highlights the importance of ensuring that the patient remains HIV uninfected during PrEP. Ongoing exposure to TDF/FTC instead of a fully suppressive antiretroviral regimen during HIV infection carries a high risk that the virus will develop resistance to TDF/FTC, along with other antiretroviral drugs.
Medication adherence counseling. Adherence counseling should be provided at the beginning of PrEP, as well as at each refill visit. The iPrEx study found that no new HIV infections occurred in participants who were 100% adherent to oral PrEP, emphasizing the importance of medication adherence to successful PrEP.
Ongoing prevention messages. These messages include but are not limited to the use of condoms, adhering to the PrEP follow-up monitoring schedule, screening and awareness about sexually transmitted infections, and behavioral risk reduction.
Although at present the only official guidance on the use of PrEP exists for the MSM population, other data also support the use of PrEP to prevent heterosexual transmission of HIV.[4] The CDC has advised that the routine use of PrEP for patients at risk for non-MSM HIV transmission should await formal Public Health Service guidelines; however, if there is an urgent need for this strategy, healthcare workers should follow the MSM guidance[2] for precautions and procedures.[5]

PrEP is an evolving strategy in HIV prevention, with numerous ongoing evaluations of TDF/FTC and other PrEP interventions, including oral and topical application of antiretroviral agents, in all groups at high risk for HIV infection. The pharmacist is in an optimal position to monitor and educate patients on the appropriate use of PrEP, application of treatment guidelines, and the rapidly accumulating clinical trial data.

References

Centers for Disease Control and Prevention. CDC Fact Sheet. Estimates of new HIV infections in the United States, 2006-2009. August 2011. Available at: http://www.cdc.gov/nchhstp/newsroom/docs/HIV-Infections-2006-2009.pdf Accessed March 10, 2012.
Centers for Disease Control and Prevention. Interim guidance: preexposure prophylaxis for the prevention of HIV infection in men who have sex with men. MMWR Morb Mortal Wkly Rep. 2011; 60:65-68. Abstract
Grant RM, Lama JR, Anderson PL, et al; iPrEx Study Team. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010; 363:2587-2599. Abstract
Baeten J, Donnell D, Ndase P, et al; Partners PrEP Study Team. Antiretroviral PrEP for HIV-1 prevention among heterosexual men and women. Program and abstracts of the19th Conference on Retroviruses and Opportunistic Infections; March 5-8, 2012; Seattle, Washington. Abstract 29
Centers for Disease Control and Prevention. Pre-Exposure Prophylaxis (PrEP). Available at: http://www.cdc.gov/hiv/prep/ Accessed March 22, 2012.