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Secondary Prevention of HIV in the United States: Past, Current, and Future Perspectives

Fisher, Jeffrey D PhD; Smith, Laramie R BA; Lenz, Erin M BA

JAIDS Journal of Acquired Immune Deficiency Syndromes: 15 December 2010 - Volume 55 - Issue - pp S106-S115
doi: 10.1097/QAI.0b013e3181fbca2f
Supplement Article

To provide a synopsis of past, current, and potential next-generation approaches to prevention for positives (PfP) interventions in the United States. For a variety of reasons, PfP interventions, with the goals of limiting HIV transmission from people living with HIV/AIDS (PLWHA) to others and protecting the health of PLWHA, did not appear with any frequency in the United States until about 2000. Even today, the number and breadth of evidence-based PfP interventions is very limited. Nevertheless, meta-analytic evidence demonstrates that such interventions can be effective, perhaps even more so than interventions targeting HIV-uninfected individuals. We review early and more recent PfP interventions and suggest that next-generation PfP interventions must involve behavioral and biologic components and target any element that affects HIV risk behavior and/or infectivity. Next-generation PfP interventions should include increased HIV testing to identify additional PLWHA, components to initiate and maintain HIV care, to initiate antiretroviral therapy and promote adherence, and to reduce sexual and injection drug use risk behavior, as well as ancillary treatments and referrals to services. Comprehensive next-generation PfP interventions, including all of these elements and effective linkages among them, are discussed.

From the Center for Health, Intervention, and Prevention, University of Connecticut, Storrs, CT.

Supported by the National Institute of Mental Health Grant R01MH077524-04, integrating HIV prevention into care for people living with HIV/AIDS in South Africa.

Presented in part at the HIV Prevention Trials Network Annual Meeting, May 4-8, 2009, National Harbor, MD, and the XVIII International AIDS Conference, July 18-23, 2010, Vienna, Austria.

The authors have no funding or conflicts of interest to disclose.

Correspondence to: Jeffrey D. Fisher, PhD, Center for Health, Intervention, and Prevention, University of Connecticut, 2006 Hillside Road, Unit 1248, Storrs, CT 06269-1248 (email:

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Prevention for positive (PfP) interventions are supportive prevention efforts administered to people living with HIV/AIDS (PLWHA) and tailored to their needs. They involve behavioral and biologic strategies (Fig. 1., components B-G) that can benefit the public health by limiting HIV transmission to others and, at the same time, can protect the health of PLWHA by lowering their likelihood of acquiring other pathogens.1-4 The rationale for PfP interventions as a critical element of HIV prevention involves the fact that all “new” HIV infections must begin with an HIV-positive individual, and the finding that some PLWHA who are aware of their antibody status continue to practice risky behavior.5-9 For these reasons, from an HIV prevention perspective, it can be highly efficient to intervene with PLWHA3,10 and highly effective.1,11,12 Strengthening this argument is that because large numbers of PLWHA are on antiretroviral therapy (ART), HIV prevalence in the United States will continue to rise,3,13 along with the number of individuals capable of transmitting HIV, and even drug resistant HIV, through risky behavior.1,3

About 1.1 million Americans are living with HIV,13,14 75% to 80% of whom are aware of their antibody status.13,15,16 About one third of these PLWHA continue to engage in risk behaviors that can transmit HIV to others.5-9 Reasons vary widely and include dynamics such as lack of critical information, motivation, and behavioral skills needed to practice safer behaviors, alcohol and drug use, mental health issues, extreme poverty, and intimate partner violence, among others. These have been reviewed elsewhere.1,17-20

Despite a critical need, PfP interventions were rare until 2 decades into the US epidemic.21 The delay in funding and addressing the prevention needs of PLWHA likely occurred because US policy was late in prioritizing this issue. For reasons synthesized in a recent article,21 policies and programmatic approaches highlighting the importance of PfP emerged only circa 2000.22-24

A review article in 2000 described PfP as a “new issue.”25,26 In fact, to date, the vast majority of HIV prevention interventions in the United States have not focused on the HIV prevention needs of PLWHA. Literally, hundreds of HIV prevention intervention studies and many meta-analytic reviews of this work have been published, and almost all the populations targeted in this work were selected for characteristics other than serostatus.11,21,27 As reported in study by W. Fisher et al,21 of 898 HIV prevention interventions between 1988 and 2006 identified in a research synthesis project database of the US Centers for Disease Control, only 6.6% were directed at PLWHA, most occurring after 2000. The overall dearth of evidence-based PfP interventions is also manifest in the very small number of such interventions identified by the US Centers for Disease Control as “best” or “promising evidence” and targeted for widespread dissemination.21 This is the case despite strong arguments that PfP interventions, which focus, in part, on serostatus and its effect on HIV risk and preventive behavior, are a critical component of an effective comprehensive approach to HIV prevention.1,3,10,21,23,28,29

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The first 2 meta-analytic reviews of PfP interventions were conducted on trials published before early 2005 and involved outcomes on sexual risk behavior,11,12 sexually transmitted infections (STI),11 and drug use risk behavior.11 Eighteen distinct interventions, meeting strict criteria, were included in these meta-analyses. All but 2 interventions were conducted exclusively within the United States and 14 exclusively targeted PLWHA. Across both meta-analyses, PfP interventions effectively reduced the sexual risk, particularly instances of unprotected vaginal or anal intercourse, and did so more effectively than earlier interventions with seronegative populations. Crepaz et al11 also found that PfP interventions targeting biologic end points were effective in reducing STI incidence. However, significant reductions were not observed in the number of sex partners12 and in needle-sharing outcomes.11 Nevertheless, Crepaz et al11 concluded that the overall magnitude of sexual risk reduction observed across all interventions and end points reviewed implied that PfP would likely be cost-effective in terms of larger-scale health benefits. Meta-analyses also identified specific PfP intervention elements with respect to intervention design (eg, theoretically based; individual vs group level), content, delivery (eg, by a health care provider or professional counselor), and population characteristics, related to more effective outcomes.11,12

Our own program of PfP research, the Options Project, was funded by the National Institute of Mental Health in 1999 to develop, implement, and rigorously evaluate a PfP intervention delivered by HIV-care providers with PLWHA in a clinical care setting. It was based on the information-motivation-behavioral (IMB) skills model of HIV risk and prevention.30-32 In terms of the model, HIV risk behavior in PLWHA, and others, is often associated with weaknesses in individuals' levels of HIV prevention IMB. Individual-level PfP interventions, which address these elements, should lead to sustained increases in HIV prevention. Options involved having providers assess the IMB dynamics of patients' HIV risk behavior and intervene to remediate any weaknesses. Some US studies revealed that these brief interventions, embedded in regular patient care, led to significant and sustained changes in patient risk behavior.10,28

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Since the two 2006 meta-analyses, additional PfP intervention trials have been published. Two descriptive reviews published in 2009 identified 7 new intervention outcome studies and 14 characterizations of interventions under development or investigation. Across both reviews, PfP interventions continued to be effective across a variety of intervention design and delivery processes.1,33

Table 1 summarizes all US PfP interventions with behavioral or biologic outcomes conducted, evaluated, and published between January 1, 2005 (the approximate cutoff for the two 2006 meta-analyses), and July 13, 2010. We utilized all search terms [Search terms were combined as follows, Group 1 (OR between each term): HIV positive, prevention with positives, prevention for positives, positive prevention, HIV prevention with positives, HIV/AIDS prevention with positives, secondary HIV prevention. Group 2 (OR between each term): prevention, HIV prevention, HIV counseling, transmission, risk behavior, risk reduction, harm reduction. Combine Group 1 AND Group 2 AND intervention.] provided in all previous reviews.1,11,12,33 Eighteen PfP interventions reporting behavioral or biologic outcomes10,34-50 are depicted in Table 1. Twenty-seven additional studies were identified reporting intermediate prebehavioral outcomes (eg, information, self-efficacy)51-53 or characterizing intervention development and implementation processes.29,54-76 All were identified through searches in PubMed, Psych Info, Cumulative Index to Nursing and Allied Health (CINAHL), and the previous reviews.

Across the 18 studies with behavioral or biologic outcomes, PfP interventions continue to be effective, with all but 3 reducing targeted sexual and/or drug-related risk behaviors; Table 1 provides specifics of relevant studies. Most of the interventions contained elements consistent with those identified earlier as contributing to effective outcomes.11,12 For example, most were developed using one10,37,46-48,50 or more34,38,40-42,45,49 health-behavior theories and were delivered in either an HIV clinic10,35,36,38,39,42,43,45,48,49 or another HIV service venue40,44 and by professional counselors/therapists40,41,43,44,48,50 or HIV care providers/other medical staff.1,35,39,49 A relatively small number of interventions targeted multiple HIV risk-related behaviors (eg, increasing disclosure, reducing heavy drinking or drug use, or enhancing coping skills36,37,40-45,48,50) and targeted biologic transmission risk factors (eg, increased adherence to ART, reduced viral load37,40,42-45). Compared with previous reviews,1,11,33 we note an increase in the number of PfP interventions tailored to risk dynamics unique to specific subpopulations of PLWHA (eg, decreasing sexual risk in substance-using seropositive MSM).34,40,41,45-47,50,76 Future meta-analysis should evaluate the effectiveness of emerging efforts to use multicomponent and more tailored intervention approaches to reduce overall transmission risk.

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We believe that a synergistic package of PfP interventions at the intersection of behavior and biology will have optimal impact on limiting HIV transmission and maintaining PLWHA health.1-4,77 In Figure 1, we identify vital components and linkages of a comprehensive behavioral-biomedical conceptualization of next-generation PfP interventions (with an alphanumeric system denoting the various components and paths as well as “movement” within the model, eg, to component C from component B via path i).

All components and linkages need to be copresent and integrated in such an approach. To date, these elements remain separate unintegrated components of HIV prevention and of treatment science for PLWHA. Finally, we emphasize that the model must be evaluated and supported over the disease course of PLWHA (component A), understanding that what is needed to optimize the effect of each component and path may vary by disease stages78 and subpopulations (eg, PLWHA who are MSM vs injection drug user; young vs older PLWHA; incarcerated vs unincarcerated PLWHA; PLWHA with different comorbid conditions38,39,43,48,57,77,79-81).

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Increased HIV testing (component B) is a critical element in next-generation PfP. This will identify PLWHA who were previously unaware of their serostatus. When individuals learn that they are HIV infected, substantial, self-initiated, postdiagnosis reductions in risk behavior often follow.82,83 Testing may also help reduce the number of PLWHA unaware of their status during periods of increased infectiousness (ie, acute, symptomatic, and late stages), which can affect transmission.4,78 Achieving postdiagnosis linkages to HIV care (component C, path i) to reduce biologic risk of transmission (eg, through identification and treatment of STIs and access to ART medications), as well as ensuring linkages to ancillary services (component G, path x) to address behavioral risk-related contextual factors, are essential.

Initiating and maintaining HIV care (component C) aims to facilitate routine primary care visits and continued monitoring of patients' overall health.84 Routine appointments have been related to lower levels of behavioral79,85,86 and biologic risk (eg, treatment of existing STIs, increased viral suppression, decreased resistance),87-89 whereas prolonged absences from care relate to poorer health outcomes.90,91 Routine care provides ongoing opportunities to reduce biologic transmission through ART initiation (component D, path ii), sustained ART monitoring, and adherence support (component E, path iii). Behavioral risk reduction ideally integrates PfP support (component F, path iv) and referral to ancillary services (component G, path v), addressing contextual risk factors such as social isolation or depression.4,86,92,93

Initiation of ART (component D) rapidly curbs viral replication and reduces the amount of viral load present in plasma or genital tracts, reducing biologic risk of transmission and facilitating overall health.94-97 The relationship between risk behaviors and being on ART or achieving viral suppression is complex. Any increases in risk behavior are likely a result of treatment-related beliefs98 and underlying contextual risk factors,2,18,92 not individuals' receipt of ART or a suppressed viral load, per se.98 As biologic risk reduction requires sustaining health and high levels of adherence, support in both continuing routine HIV care (component C, path ii) and initial99 and ongoing access to ART adherence support (component E, path vi) are needed.94,96,100

ART adherence behavioral interventions (component E) sustain viral suppression through enhancing adherence behaviors. Optimal adherence decreases biologic risk by controlling both viral replication and the potential to develop treatment resistance.94,96,101 Meta-analyses report that adherence interventions significantly improve adherence behavior96,101 and support viral suppression.101 Co-occurrence of both nonadherence and HIV risk behaviors are often identified, likely resulting from common underlying barriers (eg, substance use, social isolation, psychological distress/depression).2,18,92 Integration with ongoing PfP behavioral support (component F, path vii) and referral to ancillary services (component G, path viii) to address root contextual risks4,18,92 can strengthen adherence.

PfPs behavioral interventions (component F) support safer sex and drug use behaviors, and overall health of PLWHA. Meta-analyses of PfP interventions discussed earlier demonstrate their efficacy in reducing behavioral11,12 and potentially biologic risk (ie, STIs11). In the context of existing ART, future PfP interventions need to address ART-related beliefs98 and integrate ART adherence support (component E, path vii). Referrals to or incorporation of ancillary services to address root contextual risks (component G, path ix) are also critical.1,3,48,80,102

Ancillary treatments and referrals to services (component G) address contextual factors and vulnerabilities that may undermine necessary health behaviors (eg, ability to maintain care, medication adherence, or risk reduction) through referrals to treatment and support services (see a sample list of services in box for component G in Fig. 1). These referrals may emanate from HIV testing (component B, path x), HIV care (component C, path v), adherence interventions (component E, path viii), and PfP behavioral interventions (component F, path ix), among other sources. Simultaneously, PLWHA receiving ancillary treatments or services and who are in need of testing, medical care, and behavioral support for existing adherence and risk reduction issues should be identified and connected to other components, as appropriate. For example, HIV testing for high-risk individuals (component B, path x), reengaging PLWHA not in HIV care or who never initiated care postdiagnosis (component C, path v), and providing access to existing adherence (component E, path viii) and risk reduction (component F, path ix) behavioral interventions are critical.

Due to space limitations, our discussion of a comprehensive behavioral-biomedical approach to PfP addresses model components and their links in a somewhat arbitrary linear fashion. We recognize that the need for any component and relevant linkages could occur along paths not discussed. The next generation of PfP interventions must attend to reducing both behavioral and biologic risk factors across the components in Figure 1 and ensure the linkages among them. Fortunately, some emerging PfP interventions are beginning to incorporate elements of behavioral and biologic risk reduction, but they are not comprehensive and the links are not always fleshed out.37,43,45 Future PfP intervention development needs to ensure that the linkages among these components are maintained, enhanced, and evaluated.

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positive prevention; secondary prevention of HIV; prevention for positives interventions; HIV prevention; people living with HIV; behavioral-biologic interventions

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