Sunday, December 6, 2015

#HIV: Pre-Exposure Prophylaxis (PrEP)

"Pre-exposure prophylaxis, or PrEP, is a way for people who do not have HIV but who are at substantial risk of getting it to prevent HIV infection by taking a pill every day. The pill (brand name Truvada) contains two medicines (tenofovir and emtricitabine) that are used in combination with other medicines to treat HIV. When someone is exposed to HIV through sex or injection drug use, these medicines can work to keep the virus from establishing a permanent infection.

When taken consistently, PrEP has been shown to reduce the risk of HIV infection in people who are at high risk by up to 92%. PrEP is much less effective if it is not taken consistently." - CDC

CDC Guidelines


May 14, 2014 -

  • Daily oral PrEP with the fixed-dose combination of tenofovir disoproxil fumarate (TDF) 300 mg and emtricitabine (FTC) 200 mg has been shown to be safe and effective in reducing the risk of sexual HIV acquisition in adults; therefore,
    • PrEP is recommended as one prevention option for sexually-active adult MSM (men who have sex with men) at substantial risk of HIV acquisition (IA)1
    • PrEP is recommended as one prevention option for adult heterosexually active men and women who are at substantial risk of HIV acquisition. (IA)
    • PrEP is recommended as one prevention option for adult injection drug users (IDU) at substantial risk of HIV acquisition. (IA)
    • PrEP should be discussed with heterosexually-active women and men whose partners are known to have HIV infection (i.e., HIV-discordant couples) as one of several options to protect the uninfected partner during conception and pregnancy so that an informed decision can be made in awareness of what is known and unknown about benefits and risks of PrEP for mother and fetus (IIB)
  • Currently the data on the efficacy and safety of PrEP for adolescents are insufficient. Therefore, the risks and benefits of PrEP for adolescents should be weighed carefully in the context of local laws and regulations about autonomy in health care decision-making by minors. (IIIB) 
  • Acute and chronic HIV infection must be excluded by symptom history and HIV testing immediately before PrEP is prescribed. (IA) 
  • The only medication regimen approved by the Food and Drug Administration and recommended for PrEP with all the populations specified in this guideline is daily TDF 300 mg co-formulated with FTC 200 mg (Truvada) (IA)
    • TDF alone has shown substantial efficacy and safety in trials with IDUs and heterosexually active adults and can be considered as an alternative regimen for these populations, but not for MSM, among whom its efficacy has not been studied. (IC)
    • The use of other antiretroviral medications for PrEP, either in place of or in addition to TDF/FTC (or TDF) is not recommended. (IIIA)
    • The prescription of oral PrEP for coitally-timed or other noncontinuous daily use is not recommended. (IIIA)
  • HIV infection should be assessed at least every 3 months while patients are taking PrEP so that those with incident infection do not continue taking it. The 2-drug regimen of TDF/FTC is inadequate therapy for established HIV infection, and its use may engender resistance to either or both drugs. (IA)

  • Renal function should be assessed at baseline and monitored at least every 6 months while patients are taking PrEP so that those in whom renal failure is developing do not continue to take it. (IIIA)
  • When PrEP is prescribed, clinicians should provide access, directly or by facilitated referral, to proven effective risk-reduction services. Because high medication adherence is critical to PrEP efficacy but was not uniformly achieved by trial participants, patients should be encouraged and enabled to use PrEP in combination with other effective prevention methods. (IIIA)

Affected Communities:

  • LGBT People of Color
    • Black and Latino men

Access:


You can get prep from any healthcare provider that specializes in HIV prevention in your local area. Many providers offer PrEP free of charge, but if you encounter a barrier to access here are some resources.

If you have insurance:
  • The Gilead Co-pay Coupon Card can help eligible uninfected individuals save on a TRUVADA for PrEP co-pay.* For more information, visit www.GileadCoPay.com or call 1-877-505-6986
If you don't have insurance:

  • Gilead’s U.S. Medication Assistance Program - This program provides assistance to uninfected individuals in the United States who do not have insurance or who need financial assistance. As part of this program, Gilead provides assistance for uninfected individuals who are eligible and who cannot afford to pay for TRUVADA for PrEP. To learn about eligibility, contact Gilead’s U.S. Medication Assistance Program at 1-855-330-5479between 9:00 a.m. and 8:00 p.m. (Eastern). You can also download the enrollment form to be completed by your client and your client’s healthcare provider.Partnership for Prescription Assistance (PPA) Program
  • Partnership for Prescription Assistance (PPA) Program -This program is designed to help uninsured Americans get the prescription medicines they need at no or low cost. Your clients can find out if they are eligible by calling 1-888-4PPA-NOW 
  • (1-888-477-2669) or visiting the PPA Website at www.pparx.org.
If any of your clients do not have insurance, help may also be available through:


Origins

The Clinical Trials:

There were four clinical trials conducted, these trials are the foundation for what is now PrEP: 

December 30, 2010 -


  • BACKGROUND

    Antiretroviral chemoprophylaxis before exposure is a promising approach for the prevention of human immunodeficiency virus (HIV) acquisition.

    METHODS

    We randomly assigned 2499 HIV-seronegative men or transgender women who have sex with men to receive a combination of two oral antiretroviral drugs, emtricitabine and tenofovir disoproxil fumarate (FTC–TDF), or placebo once daily. All subjects received HIV testing, risk-reduction counseling, condoms, and management of sexually transmitted infections.

    RESULTS

    The study subjects were followed for 3324 person-years (median, 1.2 years; maximum, 2.8 years). Of these subjects, 10 were found to have been infected with HIV at enrollment, and 100 became infected during follow-up (36 in the FTC–TDF group and 64 in the placebo group), indicating a 44% reduction in the incidence of HIV (95% confidence interval, 15 to 63; P=0.005). In the FTC–TDF group, the study drug was detected in 22 of 43 of seronegative subjects (51%) and in 3 of 34 HIV-infected subjects (9%) (P<0.001). Nausea was reported more frequently during the first 4 weeks in the FTC–TDF group than in the placebo group (P<0.001). The two groups had similar rates of serious adverse events (P=0.57).

    CONCLUSIONS

    Oral FTC–TDF provided protection against the acquisition of HIV infection among the subjects. Detectable blood levels strongly correlated with the prophylactic effect. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT00458393.)
July 11 2012 -


  • Abstract

    Introduction

    Antiretroviral pre-exposure prophylaxis (PrEP) reduces the incidence of acquisition of human immunodeficiency virus type 1 (HIV-1) in men who have sex with men and is a promising approach for preventing HIV-1 in heterosexual populations.

    Methods

    We conducted a randomized, three-arm trial of oral antiretroviral PrEP among heterosexual couples from Kenya and Uganda in which one member was HIV-1 seronegative and the other HIV-1 seropositive. Seronegative partners were randomly assigned to once-daily tenofovir (TDF), combination emtricitabine/tenofovir (FTC/TDF), or matching placebo and followed monthly for up to 36 months. At enrollment, HIV-1 seropositive partners were not eligible for antiretroviral therapy under national guidelines. All couples received standard HIV-1 treatment and prevention services, including individual and couples risk-reduction counseling and condoms.

    Results

    4758 couples were enrolled; for 62%, the HIV-1 seronegative partner was male. For HIV-1 seropositive participants, the median CD4 count was 495 cells/μL (interquartile range 375–662). Of 82 post-randomization HIV-1 infections, 17 were among those assigned TDF (incidence 0.65 per 100 person-years), 13 among those assigned FTC/TDF (incidence 0.50 per 100 person-years), and 52 among those assigned placebo (incidence 1.99 per 100 person-years), indicating a 67% relative reduction in HIV-1 incidence for TDF (95% CI 44 to 81, p<0.001) and 75% for FTC/TDF (95% CI 55 to 87, p<0.001). HIV-1 protective effects of FTC/TDF and TDF were not significantly different (p=0.23), and both study medications significantly reduced HIV-1 incidence in both men and women. The rate of serious medical events was similar across the study arms.

    Conclusions

    Oral TDF and FTC/TDF provided substantial protection against HIV-1 acquisition in heterosexual men and women, with comparable efficacy of TDF and FTC/TDF. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number NCT00557245)
    Keywords: HIV-1 serodiscordant couples, pre-exposure prophylaxis, HIV-1 prevention, randomized clinical trial, Africa.

August 2, 2012 -


BACKGROUND

Preexposure prophylaxis with antiretroviral agents has been shown to reduce the transmission of human immunodeficiency virus (HIV) among men who have sex with men; however, the efficacy among heterosexuals is uncertain.
  • METHODS

    We randomly assigned HIV-seronegative men and women to receive either tenofovir disoproxil fumarate and emtricitabine (TDF–FTC) or matching placebo once daily. Monthly study visits were scheduled, and participants received a comprehensive package of prevention services, including HIV testing, counseling on adherence to medication, management of sexually transmitted infections, monitoring for adverse events, and individualized counseling on risk reduction; bone mineral density testing was performed semiannually in a subgroup of participants.

    RESULTS

    A total of 1219 men and women underwent randomization (45.7% women) and were followed for 1563 person-years (median, 1.1 years; maximum, 3.7 years). Because of low retention and logistic limitations, we concluded the study early and followed enrolled participants through an orderly study closure rather than expanding enrollment. The TDF–FTC group had higher rates of nausea (18.5% vs. 7.1%, P<0.001), vomiting (11.3% vs. 7.1%, P=0.008), and dizziness (15.1% vs. 11.0%, P=0.03) than the placebo group, but the rates of serious adverse events were similar (P=0.90). Participants who received TDF–FTC, as compared with those who received placebo, had a significant decline in bone mineral density. K65R, M184V, and A62V resistance mutations developed in 1 participant in the TDF–FTC group who had had an unrecognized acute HIV infection at enrollment. In a modified intention-to-treat analysis that included the 33 participants who became infected during the study (9 in the TDF–FTC group and 24 in the placebo group; 1.2 and 3.1 infections per 100 person-years, respectively), the efficacy of TDF–FTC was 62.2% (95% confidence interval, 21.5 to 83.4; P=0.03).

    CONCLUSIONS

    Daily TDF–FTC prophylaxis prevented HIV infection in sexually active heterosexual adults. The long-term safety of daily TDF–FTC prophylaxis, including the effect on bone mineral density, remains unknown. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health; TDF2 ClinicalTrials.gov number,NCT00448669.)
June 13 2013 - 

  • Summary

    Background

    Antiretroviral pre-exposure prophylaxis reduces sexual transmission of HIV. We assessed whether daily oral use of tenofovir disoproxil fumarate (tenofovir), an antiretroviral, can reduce HIV transmission in injecting drug users.

    Methods

    In this randomised, double-blind, placebo-controlled trial, we enrolled volunteers from 17 drug-treatment clinics in Bangkok, Thailand. Participants were eligible if they were aged 20–60 years, were HIV-negative, and reported injecting drugs during the previous year. We randomly assigned participants (1:1; blocks of four) to either tenofovir or placebo using a computer-generated randomisation sequence. Participants chose either daily directly observed treatment or monthly visits and could switch at monthly visits. Participants received monthly HIV testing and individualised risk-reduction and adherence counselling, blood safety assessments every 3 months, and were offered condoms and methadone treatment. The primary efficacy endpoint was HIV infection, analysed by modified intention-to-treat analysis. This trial is registered withClinicalTrials.gov, number NCT00119106.

    Findings

    Between June 9, 2005, and July 22, 2010, we enrolled 2413 participants, assigning 1204 to tenofovir and 1209 to placebo. Two participants had HIV at enrolment and 50 became infected during follow-up: 17 in the tenofovir group (an incidence of 0·35 per 100 person-years) and 33 in the placebo group (0·68 per 100 person-years), indicating a 48·9% reduction in HIV incidence (95% CI 9·6–72·2; p=0·01). The occurrence of serious adverse events was much the same between the two groups (p=0·35). Nausea was more common in participants in the tenofovir group than in the placebo group (p=0·002).

    Interpretation

    In this study, daily oral tenofovir reduced the risk of HIV infection in people who inject drugs. Pre-exposure prophylaxis with tenofovir can now be considered for use as part of an HIV prevention package for people who inject drugs.

    Funding

    US Centers for Disease Control and Prevention and the Bangkok Metropolitan Administration.