Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents
Preventing Secondary Transmission of HIV
(Last updated:3/27/2012; last reviewed:3/27/2012)
Despite substantial advances in prevention and treatment of HIV infection in the United States, the rate of new infections has remained stable [1-2]. Although earlier prevention interventions mainly were behavioral, recent data demonstrate the strong impact of antiretroviral therapy (ART) on secondary HIV transmission. The most effective strategy to stem the spread of HIV will probably be a combination of behavioral, biological, and pharmacological interventions .
Counseling and related behavioral interventions for those living with HIV infection can reduce behaviors associated with secondary transmission of HIV. Each patient encounter offers the clinician an opportunity to reinforce HIV prevention messages, but multiple studies show that prevention counseling is frequently neglected in clinical practice [4-5]. Although delivering effective prevention interventions in a busy practice setting may be challenging, clinicians should be aware that patients often look to their providers for messages about HIV prevention. Multiple approaches to prevention counseling are available, including formal guidance from the Centers for Disease Control and Prevention (CDC) for incorporating HIV prevention into medical care settings. Such interventions have been demonstrated to be effective in changing sexual risk behavior [6-8] and can reinforce self-directed behavior change early after diagnosis .
CDC has identified several prevention interventions for individuals infected with HIV that meet stringent criteria for efficacy and scientific rigor (http://www.cdc.gov/hiv/topics/research/prs/index.htm). The following three interventions have proven effective in treatment settings and can be delivered by providers as brief messages during clinic visits:
In addition, CDC’s “Prevention Is Care” campaign (http://www.actagainstaids.org/provider/pic/index.html) helps providers (and members of a multidisciplinary care team) integrate simple methods to prevent transmission by HIV-infected individuals into routine care. These prevention interventions are designed to reduce the risk of secondary HIV transmission through sexual contact. The interventions are designed generally for implementation at the community or group level, but some can be adapted and administered in clinical settings by a multidisciplinary care team.
Need for Screening for High-Risk Behaviors
The primary care visit provides an opportunity to screen patients for ongoing high-risk drug and sexual behaviors for transmitting HIV infection. Routine screening and symptom-directed testing for and treatment of sexually transmitted diseases (STDs), as recommended by CDC , remain essential adjuncts to prevention counseling. Genital ulcers may facilitate HIV transmission and STDs may increase HIV viral load in plasma and genital secretions [7, 11-13]. They also provide objective evidence of unprotected sexual activity, which should prompt prevention counseling.
The contribution of substance and alcohol use to HIV risk behaviors and transmission has been well established in multiple populations [14-18]; therefore, effective counseling for injection and noninjection drug users is essential to prevent HIV transmission. Identifying the substance(s) of use is important because HIV prevalence, transmission risk, risk behaviors, transmission rates, and potential for pharmacologic intervention all vary according to the type of substance used [19-21]. Risk-reduction strategies for injection drug users (IDUs), in addition to condom use, include needle exchange and instructions on cleaning drug paraphernalia. Evidence supporting the efficacy of interventions to reduce injection drug use risk behavior also exists. Interventions include both behavioral strategies [14-15, 22] and opiate substitution treatment with methadone or buprenorphine [23-24]. No successful pharmacologic interventions have been found for cocaine and methamphetamine users; cognitive and behavioral interventions demonstrate the greatest effect on reducing the risk behaviors of these users [25-27]. Given the significant impact of cocaine and methamphetamine on sexual risk behavior, reinforcement of sexual risk-reduction strategies is important [14-18, 28].
Antiretroviral Therapy as Prevention
ART can play an important role in preventing HIV transmission. Lower levels of plasma HIV RNA have been associated with decreases in the concentration of virus in genital secretions [29-32]. Observational studies have demonstrated the association between low serum or genital HIV RNA and a decreased rate of HIV transmission among serodiscordant heterosexual couples [29,33-34]. Ecological studies of communities with relatively high concentrations of men who have sex with men (MSM) and IDUs suggest increased use of ART is associated with decreased community viral load and reduced rates of new HIV diagnoses [35-37]. These data suggest that the risk of HIV transmission is low when an individual’s viral load is below 400 copies/mL [35, 38], but the threshold below which transmission of the virus becomes impossible is unknown. Furthermore, to be effective at preventing transmission it is assumed that: (1) ART is capable of durably and continuously suppressing viremia; (2) adherence to an effective ARV regimen is high; and (3) there is an absence of a concomitant STD. Importantly, detection of HIV RNA in genital secretions has been documented in individuals with controlled plasma HIV RNA and data describing a differential in concentration of most ARV drugs in the blood and genital compartments exist [30, 39]. At least one case of HIV transmission from a patient with suppressed plasma viral load to a monogamous uninfected sexual partner has been reported .
In the HPTN 052 trial in HIV-discordant couples, the HIV-infected partners who were ART naive and had CD4 counts between 350 and 550 cells/mm3 were randomized to initiate or delay ART. In this study, those who initiated ART had a 96% reduction in HIV transmission to the uninfected partners . Almost all of the participants were in heterosexual relationships, all participants received risk-reduction counseling, and the absolute number of transmission events was low: 1 among ART initiators and 27 among ART delayers. Over the course of the study virologic failure rates were less than 5%, a value much lower than generally seen in individuals taking ART for their own health. These low virologic failure rates suggest high levels of adherence to ART in the study, which may have been facilitated by the frequency of study follow-up (study visits were monthly) and by participants’ sense of obligation to protect their uninfected partners. Therefore, caution is indicated when interpreting the extent to which ART for the HIV-infected partner protects seronegative partners in contexts where adherence and, thus, rates of continuous viral suppression, may be lower. Furthermore, for HIV-infected MSM and IDUs, biological and observational data suggest suppressive ART also should protect against transmission, but the actual extent of protection has not been established.
Rates of HIV risk behaviors can increase coincidently with the availability of potent combination ART, in some cases almost doubling compared with rates in the era prior to highly effective therapy . A meta-analysis demonstrated that the prevalence of unprotected sex acts was increased in HIV-infected individuals who believed that receiving ART or having a suppressed viral load protected against transmitting HIV . Attitudinal shifts away from safer sexual practices since the availability of potent ART underscore the role of provider-initiated HIV prevention counseling. With wider recognition that effective treatment decreases the risk of HIV transmission, it is particularly important for providers to help patients understand that a sustained viral load below the limits of detection will dramatically reduce but does not absolutely assure the absence of HIV in the genital and blood compartments and, hence, the inability to transmit HIV to others [41-42].
Maximal suppression of viremia not only depends on the potency of the ARV regimen used but also on the patient’s adherence to prescribed therapy. Suboptimal adherence can lead to viremia that not only harms the patient but also increases his/her risk of transmitting HIV (including drug-resistant strains) via sex or needle sharing. Screening for and treating behavioral conditions that can impact adherence, such as depression and alcohol and substance use, improve overall health and reduce the risk of secondary transmission.
Consistent and effective use of ART resulting in a sustained reduction in viral load in conjunction with consistent condom usage, safer sex and drug use practices, and detection and treatment of STDs are essential tools for prevention of sexual and blood-borne transmission of HIV. Given these important considerations, medical visits provide a vital opportunity to reinforce HIV prevention messages, discuss sex- and drug-related risk behaviors, diagnose and treat intercurrent STDs, review the importance of medication adherence, and foster open communication between provider and patient.
- Prejean J, Song R, Hernandez A, et al. Estimated HIV incidence in the United States, 2006-2009. PLoS One. 2011;6(8):e17502.
- Centers for Disease Control and Prevention. HIV Surveillance Report http://www.cdc.gov/hiv/topics/surveillance/resources/reports/. 2009. Published February 2011. Accessed December 7, 2011.
- Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. Aug 11 2011;365(6):493-505.
- Mayer KH, Safren SA, Gordon CM. HIV care providers and prevention: opportunities and challenges. J Acquir Immune Defic Syndr. Oct 1 2004;37(Suppl 2):S130-132.
- Morin SF, Koester KA, Steward WT, et al. Missed opportunities: prevention with HIV-infected patients in clinical care settings. J Acquir Immune Defic Syndr. Aug 1 2004;36(4):960-966.
- Metsch LR, McCoy CB, Miles CC, Wohler B. Prevention myths and HIV risk reduction by active drug users. AIDS Educ Prev. Apr 2004;16(2):150-159.
- Johnson WD, Diaz RM, Flanders WD, et al. Behavioral interventions to reduce risk for sexual transmission of HIV among men who have sex with men. Cochrane Database Syst Rev. 2008(3):CD001230.
- Centers for Disease Control and Prevention (CDC). Evolution of HIV/AIDS prevention programs--United States, 1981-2006. MMWR Morb Mortal Wkly Rep. Jun 2 2006;55(21):597-603.
- Gorbach PM, Drumright LN, Daar ES, Little SJ. Transmission behaviors of recently HIV-infected men who have sex with men. J Acquir Immune Defic Syndr. May 2006;42(1):80-85.
- Workowski KA, Berman S. Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. Dec 17 2010;59(RR-12):1-110.
- Tanton C, Weiss HA, Le Goff J, et al. Correlates of HIV-1 genital shedding in Tanzanian women. PLoS One. 2011;6(3):e17480.
- Wright TC, Jr., Subbarao S, Ellerbrock TV, et al. Human immunodeficiency virus 1 expression in the female genital tract in association with cervical inflammation and ulceration. Am J Obstet Gynecol. Feb 2001;184(3):279-285.
- Schacker T, Ryncarz AJ, Goddard J, Diem K, Shaughnessy M, Corey L. Frequent recovery of HIV-1 from genital herpes simplex virus lesions in HIV-1-infected men. JAMA. Jul 1 1998;280(1):61-66.
- Celentano DD, Latimore AD, Mehta SH. Variations in sexual risks in drug users: emerging themes in a behavioral context. Curr HIV/AIDS Rep. Nov 2008;5(4):212-218.
- Mitchell MM, Latimer WW. Unprotected casual sex and perceived risk of contracting HIV among drug users in Baltimore, Maryland: evaluating the influence of non-injection versus injection drug user status. AIDS Care. Feb 2009;21(2):221-230.
- Colfax G, Coates TJ, Husnik MJ, et al. Longitudinal patterns of methamphetamine, popper (amyl nitrite), and cocaine use and high-risk sexual behavior among a cohort of san francisco men who have sex with men. J Urban Health. Mar 2005;82(1 Suppl 1):i62-70.
- Mimiaga MJ, Reisner SL, Fontaine YM, et al. Walking the line: stimulant use during sex and HIV risk behavior among Black urban MSM. Drug Alcohol Depend. Jul 1 2010;110(1-2):30-37.
- Ostrow DG, Plankey MW, Cox C, et al. Specific sex drug combinations contribute to the majority of recent HIV seroconversions among MSM in the MACS. J Acquir Immune Defic Syndr. Jul 1 2009;51(3):349-355.
- Sterk CE, Theall KP, Elifson KW. Who's getting the message? Intervention response rates among women who inject drugs and/or smoke crack cocaine. Prev Med. Aug 2003;37(2):119-128.
- Sterk CE, Theall KP, Elifson KW, Kidder D. HIV risk reduction among African-American women who inject drugs: a randomized controlled trial. AIDS Behav. Mar 2003;7(1):73-86.
- Strathdee SA, Sherman SG. The role of sexual transmission of HIV infection among injection and non-injection drug users. J Urban Health. Dec 2003;80(4 Suppl 3):iii7-14.
- Copenhaver MM, Johnson BT, Lee IC, Harman JJ, Carey MP. Behavioral HIV risk reduction among people who inject drugs: meta-analytic evidence of efficacy. J Subst Abuse Treat. Sep 2006;31(2):163-171.
- Hartel DM, Schoenbaum EE. Methadone treatment protects against HIV infection: two decades of experience in the Bronx, New York City. Public Health Rep. Jun 1998;113(Suppl 1):107-115.
- Metzger DS, Navaline H, Woody GE. Drug abuse treatment as AIDS prevention. Public Health Rep. Jun 1998;113(Suppl 1):97-106.
- Crawford ND, Vlahov D. Progress in HIV reduction and prevention among injection and noninjection drug users. J Acquir Immune Defic Syndr. Dec 2010;55(Suppl 2):S84-87.
- Shoptaw S, Heinzerling KG, Rotheram-Fuller E, et al. Randomized, placebo-controlled trial of bupropion for the treatment of methamphetamine dependence. Drug Alcohol Depend. Aug 1 2008;96(3):222-232.
- Heinzerling KG, Swanson AN, Kim S, et al. Randomized, double-blind, placebo-controlled trial of modafinil for the treatment of methamphetamine dependence. Drug Alcohol Depend. Jun 1 2010;109(1-3):20-29.
- Centers for Disease Control and Prevention. Methamphetamine Use and Risk for HIV/AIDS. Atlanta, GA: Centers for Disease Control and Prevention, US Dept. of Health and Human Services; Last Modified: May 3, 2007.
- Baeten JM, Kahle E, Lingappa JR, et al. Genital HIV-1 RNA predicts risk of heterosexual HIV-1 transmission. Sci Transl Med. Apr 6 2011;3(77):77ra29.
- Sheth PM, Kovacs C, Kemal KS, et al. Persistent HIV RNA shedding in semen despite effective antiretroviral therapy. AIDS. Sep 24 2009;23(15):2050-2054.
- Graham SM, Holte SE, Peshu NM, et al. Initiation of antiretroviral therapy leads to a rapid decline in cervical and vaginal HIV-1 shedding. AIDS. Feb 19 2007;21(4):501-507.
- Vernazza PL, Troiani L, Flepp MJ, et al. Potent antiretroviral treatment of HIV-infection results in suppression of the seminal shedding of HIV. The Swiss HIV Cohort Study. AIDS. Jan 28 2000;14(2):117-121.
- Hughes JP, Baeten JM, Lingappa JR, et al. Determinants of Per-Coital-Act HIV-1 Infectivity Among African HIV-1-Serodiscordant Couples. J Infect Dis. Feb 2012;205(3):358-365.
- Quinn TC, Wawer MJ, Sewankambo N, et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med. Mar 30 2000;342(13):921-929.
- Das M, Chu PL, Santos GM, et al. Decreases in community viral load are accompanied by reductions in new HIV infections in San Francisco. PLoS One. 2010;5(6):e11068.
- Montaner JS, Lima VD, Barrios R, et al. Association of highly active antiretroviral therapy coverage, population viral load, and yearly new HIV diagnoses in British Columbia, Canada: a population-based study. Lancet. Aug 14 2010;376(9740):532-539.
- Porco TC, Martin JN, Page-Shafer KA, et al. Decline in HIV infectivity following the introduction of highly active antiretroviral therapy. AIDS. Jan 2 2004;18(1):81-88.
- Attia S, Egger M, Muller M, Zwahlen M, Low N. Sexual transmission of HIV according to viral load and antiretroviral therapy: systematic review and meta-analysis. AIDS. Jul 17 2009;23(11):1397-1404.
- Cu-Uvin S, DeLong AK, Venkatesh KK, et al. Genital tract HIV-1 RNA shedding among women with below detectable plasma viral load. AIDS. Oct 23 2010;24(16):2489-2497.
- Sturmer M, Doerr HW, Berger A, Gute P. Is transmission of HIV-1 in non-viraemic serodiscordant couples possible? Antivir Ther. 2008;13(5):729-732.
- Crepaz N, Hart TA, Marks G. Highly active antiretroviral therapy and sexual risk behavior: a meta-analytic review. JAMA. Jul 14 2004;292(2):224-236.
- Rice E, Batterham P, Rotheram-Borus MJ. Unprotected sex among youth living with HIV before and after the advent of highly active antiretroviral therapy. Perspect Sex Reprod Health. Sep 2006;38(3):162-167.