美CDC更新HIV暴露前预防指南

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美国疾病控制和预防中心（CDC）近日宣布，其已更新艾滋病毒感染高风险患者的暴露前预防（PrEP）建议，包括使用注射吸毒者(IDUs)以及高风险性行为者。

  

该建议遵循了6月12日在线发表在《柳叶刀》杂志上的临床试验结果，结果显示每日口服富马酸替诺福韦（TDF）300 mg可有效减少注射吸毒者感染艾滋病毒的风险。

  

7月16日，美国食品和药物管理局批准固定剂量复方药TDF 300 mg和恩曲他滨（FTC）200 mg用于男男性行为（MSM）和性行为活跃的异性性行为者HIV性传播的PrEP。这些推荐是基于对MSM和异性性行为活跃的男性和女性进行临床试验的结果。这些试验并未评估PrEP对注射吸毒者的作用。

  

基于近日公布的试验结果，CDC推荐PrEP作为注射违禁药物的HIV高风险患者多个预防选择之一。

  

对注射吸毒者的PrEP推荐

  

每日TDF/FTC为IDUs的首选PrEP方案，原因如下：

  

•TDF/FTC包含相同剂量的TDF（300 mg），已被证明对IDUs是有效的；

  

•在PrEP试验中对两种方案进行了对比，与TDF相比，TDF/FTC未表现出额外的毒性；

  

•IDUs有性接触感染艾滋病毒的风险，为TDF/FTC的适应症。

  

•在美国，TDF/FTC被批准用于性传播艾滋病毒的PrEP。

  

对没有艾滋病毒性传播风险的患者，TDF/FTC用于预防，为标识外使用。CDC建议为IDUs提供服务，包括PrEP和减少注射和危险性行为的措施。

  

对所有个体，PrEP的使用：

  

• 禁用于HIV阳性或情况未知患者，或者估计肌酐清除率低于60 mL/min的患者；

  

• 应关注HIV感染风险非常高的****；

  

• 应作为全面预防服务的一部分；

  

• 正如以往指南的建议，应季度监测HIV状况、怀孕状况、不利影响、用药依从性和高危行为。

  

坚持日常PrEP对减少感染艾滋病毒的风险是至关重要的，在PrEP临床试验中，实现高依从性具有挑战。

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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

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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<0.001). Rates were similar in the TDF and placebo groups.
PrEP Recommendation for IDUs
On July 16, 2012, based on the results of trials in MSM and heterosexually active women and men, the Food and Drug Administration approved a label indication for the use of the fixed dose combination of TDF 300 mg and emtricitabine (FTC) 200 mg (Truvada) as PrEP against sexual HIV acquisition by MSM and heterosexually active women and men (11). These trials did not evaluate safety and efficacy among injecting-drug users.
CDC recommends that daily TDF/FTC be the preferred PrEP regimen for IDUs for the following reasons: 1) TDF/FTC contains the same dose of TDF (300 mg) proven effective for IDUs, 2) TDF/FTC showed no additional toxicities compared with TDF alone in PrEP trials that have provided both regimens, 3) IDUs also are at risk for sexual HIV acquisition for which TDF/FTC is indicated, and 4) TDF/FTC has an approved label indication for PrEP to prevent sexual HIV acquisition in the United States. Its use to prevent parenteral HIV acquisition in those without sexual acquisition risk is currently an "off-label" use. Reported injection practices that place persons at very high risk for HIV acquisition include sharing of injection equipment, injecting one or more times a day, and injection of cocaine or methamphetamine. CDC recommends that prevention services provided for IDUs receiving PrEP include those targeting both injection and sexual risk behaviors (12).
In all populations, PrEP use 1) is contraindicated in persons with unknown or positive HIV status or with an estimated creatinine clearance <60 mL/min, 2) should be targeted to adults at very high risk for HIV acquisition, 3) should be delivered as part of a comprehensive set of prevention services, and 4) should be accompanied by quarterly monitoring of HIV status, pregnancy status, side effects, medication adherence, and risk behaviors, as outlined in previous interim guidance (9,10). Adherence to daily PrEP is critical to reduce the risk for HIV acquisition, and achieving high adherence was difficult for many participants in PrEP clinical trials (Table).
Comment
Providing PrEP to IDUs at very high risk for HIV acquisition could contribute to the reduction of HIV incidence in the United States. In addition, if PrEP delivery is integrated with prevention and clinical care for the additional health concerns faced by IDUs (e.g., hepatitis B and C infection, abscesses, and overdose), substance abuse treatment and behavioral health care, and social services, PrEP will contribute additional benefits to a population with multiple life-threatening physical, mental, and social health challenges (12,13). CDC, in collaboration with other federal agencies, is preparing comprehensive U.S. Public Health Service guidelines on the use of PrEP with MSM, heterosexually active men and women, and IDUs, currently scheduled for release in 2013.
Reported by
Dawn K. Smith, MD, Michael Martin, Amy Lansky, PhD, Jonathan Mermin, MD, Div of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC. Kachit Choopanya, MD, Bangkok Tenofovir Study Group, Thailand. Corresponding contributor: Dawn K. Smith, dsmith1@cdc.gov, 404-639-5166.
References
1.        Choopanya K, Martin M, Suntharasamai P, et al. Antiretroviral prophylaxis for HIV infection among people who inject drugs in Bangkok, Thailand: a randomized, double-blind, placebo-controlled trial. Lancet. In press, June 2013.
2.        CDC. Estimated HIV incidence in the United States, 2007–2010. HIV surveillance supplemental report 2012;17(4). Available at http://www.cdc.gov/hiv/topics/su ... orts/#supplemental.
3.        CDC. HIV infection and HIV-associated behaviors among injecting drug users—20 cities, United States, 2009. MMWR 2012;61:133–8.
4.        Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010;363:2587–99.
5.        Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med 2012;367:399–410.
6.        Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med 2012;367:423–34.
7.        Van Damme L, Corneli A, Ahmed K, et al. Preexposure prophylaxis for HIV infection among African women. N Engl J Med 2012;367:411–22.
8.        Marrazzo J, Ramjee G, Nair G, et al. Pre-exposure prophylaxis for HIV in women: daily oral tenofovir, oral tenofovir/emtricitabine, or vaginal tenofovir gel in the VOICE Study (MTN 003) [Abstract]. Presented at the 20th Conference on Retroviruses and Opportunistic Infections; March 3–6, 2013; Atlanta, GA. Available at http://www.retroconference.org/2013b/abstracts/47951.htm .
9.        CDC. Interim guidance: preexposure prophylaxis for the prevention of HIV infection in men who have sex with men. MMWR 2011;60:65–8.
10.        CDC. Interim guidance for clinicians considering the use of preexposure prophylaxis for the prevention of HIV infection in heterosexually active adults. MMWR 2012;61:586–9.
11.        Food and Drug Administration. Truvada approved to reduce the risk of sexually transmitted HIV in people who are not infected with the virus. Silver Spring, MD: US Department of Health and Human Services, Food and Drug Administration; 2012. Available at http://www.fda.gov/forconsumers/ ... ities/ucm312264.htm .
12.        CDC. Integrated prevention services for HIV infection, viral hepatitis, sexually transmitted diseases, and tuberculosis for persons who use drugs illicitly: summary guidance from CDC and the U.S. Department of Health and Human Services. MMWR 2012;61(No. RR-5).
13.        Edelman EJ, Fiellin DA. Moving HIV pre-exposure prophylaxis into clinical settings: lessons from buprenorphine. Am J Prev Med 2013;44(1 Suppl 2):S86–90.

TABLE. Results from randomized, placebo-controlled, clinical trials of the efficacy of daily oral antiretroviral preexposure prophylaxis (PrEP) for preventing human immunodeficiency virus (HIV) infection

fxch

此话题非常有前沿型,,在中国能否用,期待着.

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