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发表于 2013-6-14 09:52:01
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本帖最后由 星梦78 于 2013-6-14 10:12 编辑
Update to Interim Guidance for Preexposure Prophylaxis (PrEP) for the Prevention of HIV Infection: PrEP for Injecting Drug Users
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June 14, 2013 / 62(23);463-465
Update to Interim Guidance for Preexposure Prophylaxis.docx
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On June 12, 2013, the Thailand Ministry of Health and CDC published results from a randomized controlled trial of a daily oral dose of 300 mg of tenofovir disoproxil fumarate (TDF) that showed efficacy in reducing the acquisition of human immunodeficiency virus (HIV) infection among injecting drug users (IDUs) (1). Based on these findings, CDC recommends that preexposure prophylaxis (PrEP) be considered as one of several prevention options for persons at very high risk for HIV acquisition through the injection of illicit drugs.
Background
Among the approximately 50,000 new HIV infections acquired each year in the United States, 8% were attributed to injection-drug use in 2010 (2). The National HIV Behavioral Surveillance System, surveying IDUs in 20 U.S. cities in 2009, found high frequencies of both injection-drug use and sexual practices that are associated with HIV acquisition (3). Among IDUs without HIV infection, 34% reported having shared syringes in the preceding 12 months, and 58% reported having shared injection equipment; 69% reported having unprotected vaginal sex and 23% reported having unprotected male-female anal sex. Among HIV-uninfected male IDUs, 7% reported previous male-male anal sex, and 5% reported unprotected male-male anal sex. However, only 19% of male and female IDUs reported participating in an intervention to reduce risk behaviors. These findings underscore a need to provide effective interventions to further reduce HIV infections among IDUs in the United States.
Several clinical trials have demonstrated safety and efficacy of daily oral antiretroviral PrEP for the prevention of HIV acquisition among men who have sex with men (MSM) (4) and heterosexually active men and women (5,6), although two trials were unable to show efficacy, likely because of low adherence (7,8) (Table). CDC previously has issued interim guidance for PrEP use with MSM (9) and heterosexually active adults (10) and now provides interim guidance for PrEP use in IDUs.
During 2009–2013, CDC convened workgroup meetings and consulted with external subject matter experts, including clinicians, epidemiologists, academic researchers, health department policy and program staff members, community representatives, and HIV and substance abuse subject matter experts at federal health agencies, to 1) review the results of PrEP trials and other data as they became available and 2) deliberate and recommend content for interim guidance and comprehensive U.S. Public Health Service guidelines for PrEP use in the United States. The expert opinions from the IDU workgroup and other workgroups were used to develop this interim guidance on PrEP use with IDUs.
Rationale and Evidence
The Bangkok Tenofovir Study enrolled HIV-uninfected persons who reported injecting illicit drugs in the prior year into a phase-III randomized, double-blind, placebo-controlled trial to determine the safety and efficacy of daily oral TDF to reduce the risk for HIV acquisition. In all, 2,413 eligible, consenting men and women aged 20–60 years were randomized to receive either daily oral doses of 300 mg of TDF (n = 1,204) or a placebo tablet (n = 1,209). Participants could elect to receive tablets daily by directly observed therapy or receive a 28-day supply of daily doses to take home; they could switch medication supply method at their monthly follow-up visits. At follow-up visits every 28 days, individualized adherence and risk-reduction counseling, HIV testing, pregnancy testing for women, and assessment for adverse events were conducted. An audio computer-assisted self-interview was conducted every 3 months to assess risk behaviors. Blood was collected at enrollment; months 1, 2, and 3; and then every 3 months for laboratory testing to screen for adverse reactions to the medication. At study clinics (operated by the Bangkok Metropolitan Administration), social services, primary medical care, methadone, condoms, and bleach (for cleaning injection equipment) were provided free of charge.
The study was conducted during 2005–2012, with a mean follow-up time of 4.6 years (maximum: 6.9 years) and a 24% loss to follow-up or voluntary withdrawal in the TDF group and a 23% loss in the placebo group. Participants took their study drug an average of 83.8% of days and were on directly observed therapy 86.9% of the time.
After enrollment, 50 patients acquired HIV infection: 17 in the TDF group and 33 in the placebo group. In the modified "intent-to-treat" analysis (excluding two participants later found to have been HIV-infected at enrollment), HIV incidence was 0.35 per 100 person-years in the TDF group and 0.68 per 100 person-years in the placebo group, representing a 48.9% reduction in HIV incidence (95% confidence interval [CI] = 9.6%–72.2%). Among those in an unmatched case-control study that included the 50 persons with incident HIV infection (case-patients) and 282 HIV-uninfected participants from four clinics (controls), detection of tenofovir in plasma was associated with a 70% reduction in the risk for HIV infection (CI = 2.3%–90.6%).
The rates of adverse events, serious adverse events, deaths, grade 3–4 laboratory abnormalities, and elevated serum creatinine did not differ significantly between the two groups. Reports of nausea and vomiting were higher in the TDF group than the placebo group in the first 2 months of medication use but not thereafter. No HIV infections with mutations associated with TDF resistance were identified among HIV-infected participants.
Comparing rates at enrollment with rates at 12 months of follow-up, risk behaviors decreased significantly for injecting drugs (from 62.7% to 22.7%), sharing needles (18.1% to 2.3%), and reporting multiple sexual partners (21.7% to 11.0%), and these risk behaviors remained below baseline throughout the entire period of the trial (all three comparisons, p |
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发表于 2013-6-14 09:52:00
