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Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents

Preventing Secondary Transmission of HIV

(Last updated:March 27, 2012; last reviewed:March 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 [3].

Prevention Counseling

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 [9].

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 [10], 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 [40].

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 [3]. 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 [9]. 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 [41]. 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.

Summary

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.

References

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