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Narrative Review: Antiretroviral Therapy to Prevent the Sexual Transmission of HIV-1

Myron S. Cohen, MD; Cynthia Gay, MD, MPH; Angela D.M. Kashuba, PharmD; Sally Blower, PhD; and Lynn Paxton, MD, MPH
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From the University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; University of California, Los Angeles, Los Angeles, California; and Centers for Disease Control and Prevention, Atlanta, Georgia.

Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.

Grant Support: By the National Institutes of Health (National Institute of Diabetes and Digestive and Kidney Diseases R37049381 and National Institute of Allergy and Infectious Diseases R0141935, R0154980, and U01067854) and the University of North Carolina Center for AIDS Research (P30050410). Dr. Gay has been supported by a Centers for Disease Control and Prevention Association of Teachers of Preventive Medicine Fellowship and National Institutes of Health Training Grant (T32AI07151).

Potential Financial Conflicts of Interest: Consultancies: A.D.M. Kashuba (Roche, Abbott, Boehringer Ingelheim, GlaxoSmithKline); Honoraria: A.D.M. Kashuba (Bristol-Myers Squibb, Pfizer Inc.); Grants received: A.D.M. Kashuba (Gilead Sciences, Abbott, Pfizer Inc.).

Requests for Single Reprints: Myron S. Cohen, MD, University of North Carolina at Chapel Hill, CB# 7030, 130 Mason Farm Road, 2115 Bioinformatics Building, Chapel Hill, NC 27599-7030; e-mail, mscohen@med.unc.edu.

Current Author Addresses: Dr. Cohen: University of North Carolina at Chapel Hill, CB# 7030, 130 Mason Farm Road, 2115 Bioinformatics Building, Chapel Hill, NC 27599-7030.

Dr. Gay: University of North Carolina at Chapel Hill, CB# 7030, 130 Mason Farm Road, 2112 Bioinformatics Building, Chapel Hill, NC 27599-7030.

Dr. Kashuba: School of Pharmacy, 3318 Kerr Hall, CB# 7360, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7360.

Dr. Blower: Semel Institute of Neuroscience & Human Behavior, David Geffen School of Medicine at University of California, Los Angeles, 1100 Glendon Avenue, PH2, Westwood, CA 90024.

Dr. Paxton: Epidemiology Branch, Centers for Disease Control and Prevention, 1600 Clifton Road, MS E-45, Atlanta, GA 30333.

Ann Intern Med. 2007;146(8):591-601. doi:10.7326/0003-4819-146-8-200704170-00010
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Antiretroviral therapy (ART) has prolonged and improved the lives of persons infected with HIV. Theoretically, it can also be used to prevent the transmission of HIV. The pharmacology of ART in the male and female genital tract can be expected to affect the success of the intervention, and ART agents differ considerably in their ability to concentrate in genital tract secretions. Emergency ART is considered to be the standard of care after occupational exposures to fluids or tissues infected with HIV. More recently, ART for prophylaxis after nonoccupational HIV exposures has been widely used and most countries have developed specific guidelines for its implementation. However, developing clinical trials to prove the efficacy of ART postexposure prophylaxis has not been possible. Experiments with rhesus macaques suggest that therapy must be offered as soon as possible after exposure (within 72 hours) and must be continued for 28 days. Additional nonhuman primate experiments have demonstrated protection from HIV infection with ART preexposure prophylaxis, and several clinical trials are under way to evaluate the safety and efficacy of this approach. The degree to which ART offered to infected persons reduces infectiousness is of considerable public health importance, but the question has not been sufficiently answered. This article provides a review of the data on the use of ART to prevent the sexual transmission of HIV and identify challenges to improving and clarifying this approach.


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Figure 1.
Antiretroviral drug concentrations in the male and female genital tract relative to blood plasma concentrations (ratio of genital to blood plasma concentrations).

Data from references 31 and 33 to 41. 3TC = lamivudine; ABC = abacavir; APV = amprenavir; ATV = atazanavir; d4T = stavudine; ddI = didanosine; DLV = delavirdine; EFV = efavirenz; ENF = enfuvirtide; FI = fusion inhibitor; FTC = emtricitabine; IDV = indinavir; LPV = lopinavir; ND = not detected; NFV = nelfinavir; NNRTI = nonnucleoside reverse transcriptase inhibitor; N(t)RTI = nucleotide reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; RTV = ritonavir; SQV = saquinavir; TDF = tenofovir; ZDV = zidovudine.

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Figure 2.
Algorithm for antiretroviral nonoccupational postexposure prophylaxis (nPEP).

Substantial HIV exposure is the exposure to blood, genital secretions, breast milk, or any body fluid visibly contaminated with blood of a person known to be infected with HIV. Negligible-risk exposure is exposure to urine, nasal secretions, saliva, sweat, or tears not visibly contaminated with blood, regardless of known or suspected HIV status of the source. Adapted from reference 77.

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Figure 3.
Sexual transmission of HIV.

The y-axis summarizes the peak of viral burden in semen in some patients with acute HIV. The numbers in parentheses suggest the probability of HIV transmission per episode of penile–vaginal intercourse. The shaded areas suggest the potential benefits of an intervention that lowers peak and steady-state viral burden. Reprinted with permission from reference 97. Copyright 2005 by Journal of Infectious Diseases.

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