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TREATMENT AND PREVENTIVE INTERVENTIONS |
From the Department of Psychology, University of Connecticut, Storrs, Connecticut.
Address correspondence and reprint requests to Seth Kalichman, Department of Psychology, University of Connecticut, 406 Babbidge Road, Storrs, CT 06269. E-mail: seth.k{at}uconn.edu.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONNOTESREFERENCES |
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Key Words: HIV/AIDS treatment • HIV/AIDS prevention • interventions
Abbreviations: STI = sexually transmitted infection.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONNOTESREFERENCES |
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HIV Treatment Adherence
Combination HIV treatments have had dramatic effects on reducing viral burden, increasing immune functioning, improving health and quality of life of people living with HIV/AIDS, and contributing directly to significant declines in HIV-related mortality (3). Unfortunately, not everyone who is prescribed antiretroviral therapies will realize the potential of these medications. When efficacy of treatment is assessed in clinical samples, viral suppression is not achieved and therapeutic effects are suboptimal in 30% to 70% of HIV-infected patients (4,5). Although many factors may contribute to HIV treatment failure, inconsistent adherence to the therapeutic regimen is one of the most critical factors implicated in suboptimal response to therapy (4–6). Adherence of 95% for most classes of antiretroviral therapies is now recognized as necessary for acceptable population-based viral suppression of HIV (4,7). Unfortunately, clinical studies report that 26% to 35% of HIV-positive patients have difficulty maintaining even 80% adherence (6).
Continued HIV Transmission Practices
Positive prevention focuses on addressing continued high risk for HIV transmission practices of people who know they are HIV infected. Studies have consistently found that one in three people living with HIV report continued high-risk sexual behavior and a significant number of these individuals have uninfected sex partners (8,9). Research has also shown that as many as one third of HIV-positive persons contract new sexually transmitted infections (STIs) subsequent to their HIV diagnosis (10). Brewer Metsch and Zenilman (11) conducted a retrospective chart review at sexually transmitted infection clinics and found 13% of HIV-positive clients were diagnosed with gonorrhea and 6% were diagnosed with infectious syphilis—rates that were significantly greater than those of their HIV-negative counterparts.
Interaction of HIV Treatment Adherence and Transmission Risk Behaviors
HIV treatment nonadherence and continued HIV transmission risk behavior interact at several levels. Drug resistance can arise from suboptimal HIV treatment adherence, causing substantial public health concerns about the spread of drug-resistant virus (12–14). Instances of individuals becoming infected with HIV strains that are already resistant to whole classes of antiretrovirals are now documented (14,15). High rates of drug-resistant mutations have been found among HIV-positive adults in US cities, with as many as half of all people receiving HIV/AIDS care in the US being at risk for multidrug resistance (14). Studies find the prevalence of multidrug-resistant HIV in those who are newly infected to be considerably lower (5% to 10%) than in treated populations (13); however, these percentages are increasing as sexually active people living with HIV/AIDS become experienced with HIV treatments (15).
The degree to which a person with HIV is infectious is related to their stage of disease and their treatment status. In the absence of treatment, people with HIV are most infectious in the first months and in the final years of HIV infection. It is during these two stages—the acute and end stages—that HIV is most rapidly replicating and proliferating. For example, in a widely known study conducted in Rakai, Uganda, Quinn et al. (16) showed that uninfected partners of HIV-positive persons were significantly more likely to contract HIV during times when their partner’s blood plasma viral load was highest. There seemed to be a dose-response relationship between the amount of HIV in peripheral blood and the risk for a partner becoming infected. In addition to stage of disease, HIV treatments can suppress the amount of virus in genital fluids as well as blood, thereby reducing infectiousness (17). However, nonadherence to treatment raises viral load in genital secretions just as occurs in blood. More worrisome is that STIs and other sources of local inflammation of the genital tract cause severe viral shedding, increasing infectiousness well beyond what blood viral load would suggest (17). Concerns over the potential for rapid spread of treatment-resistant variants of HIV are therefore heightened by HIV-positive men and women who continue sexual transmission risks with uninfected and unknown HIV status partners, especially when they have co-occurring STIs. The overlap between nonadherence and continued transmission risk behavior further raises concerns about the likely spread of treatment-resistant virus.
For a subset of people living with HIV, adherence to their HIV medication regimen is related to engaging in HIV transmission risk behaviors. Several studies have now reported an association between treatment nonadherence and continued risk behavior. For example, Wilson et al. (18) examined the co-occurrence of HIV treatment adherence and sexual risk behavior in women living with HIV and found that women who had missed taking their medications reported less condom use than women who were treatment adherent. Wagner et al. (19) also reported that, among couples where one partner was not HIV-infected (HIV nonconcordant), inconsistent HIV treatment adherence was associated with greater HIV transmission risk. Results of this study showed that couples engaging in unprotected vaginal and/or anal intercourse reported significantly poorer treatment adherence. Diamond et al. (20) found that >40% of people who were <95% adherent to their antiretroviral medications reported engaging in recent unprotected intercourse compared with 28% of people who were 
95% adherent. Flaks et al. (21) reported similar results showing that higher rates of risk behavior were associated with poorer HIV treatment adherence, a pattern of results reported by others (22,23).
However, the association between HIV treatment adherence and risk behavior is complex. Treatment adherence, viral load, and risk behavior are linked in different ways for different people. For some, nonadherence to treatment and therefore having a higher viral load is related to risk-taking, whereas for others, adhering to treatment and having an undetectable viral load leads to increased sexual risk behaviors. For example, in one study, men and women who were taking antiretrovirals and missed at least one dose of their medications in the past week reported significantly more sex partners, greater rates of unprotected intercourse, and less protected sex behaviors, including less protected sex with partners who were HIV negative or of unknown HIV status (23). In contrast, another study reported that individuals who experienced a change in their viral load from detectable to undetectable significantly increased their practice of unprotected intercourse (24). Reductions in viral load are expected when medications are adhered to, suggesting that improved treatment adherence leads to undetectable viral loads which in turn predicts increased risk behavior in a subset of people living with HIV/AIDS. Thus, studies have reported both positive and negative associations between adherence and risk behaviors.
Figure 1 shows two theoretical paths for HIV treatment adherence and nonadherence in relationship to risk behavior and potential infectiousness. The right side of the illustration shows how treatment adherence leads to reductions in blood plasma viral load, which can lead to the impression that one is less infectious and therefore reduces concerns about HIV transmission. Subsequent increases in sexual risk behavior can lead to STIs and other sources of local inflammation of the genital tract, which cause increased viral shedding and therefore greater infectiousness. The left side of Figure 1 shows that substance use, depression, and social isolation can facilitate both nonadherence and increased risk behaviors, both leading to greater infectiousness. Thus, adherence and nonadherence can be related to increased risk behavior but stemming from different causal paths.
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Common Correlates of HIV Treatment Nonadherence and Transmission Risk Behavior
Perhaps most central to the association between nonadherence and risk practices are the correlates that they share in common. Reviews of HIV treatment nonadherence show that depression, lack of social support, and substance use are consistently associated with missed medications (25). These same factors are among the most reliable predictors of continued high-risk behavior among people living with HIV infection (9). There are nonoverlapping factors that contribute to nonadherence (such as medication side effects) and continued risk behavior (such as positive moods and affect). However, it is the factors that they share in common that suggest the potential for integrated interventions to address both HIV treatment adherence and risk reduction.
Common Elements of Nonadherence Interventions
The majority of tested interventions to improve HIV treatment adherence have administered medications directly to patients (directly observed therapy), used dose reminders and alarms (enhanced cued memory), offered individualized advice, provided diaries and electronic recordings of doses taken(self-monitoring), and provided peer support (26). Interventions to increase HIV treatment adherence typically rely on efforts to educate patients about the hazards of nonadherence, teach patients self-reminder skills, and instruct patients on the use of timers, alarms, and other environmental cues (25).
Simoni et al. (26) reviewed randomized controlled trials of interventions to improve HIV treatment adherence. Examination of the elements described in these interventions shows that they included concerted efforts to improve behavioral skills directly tied to medication adherence. In one randomized controlled study, Tuldra et al. (27) tested an adherence improvement intervention that was derived from Social Cognitive Theory, and included information, motivation, and behavioral skills building. The study found that 94% of participants who received the cognitive behavioral intervention achieved 95% adherence compared with 69% of the control group—a significant difference. Another study observed improved adherence among persons who received a single session of cognitive-behavioral intervention that included motivational interviewing and problem-solving techniques (28). Weber et al. (29) found that an individual counseling cognitive behavioral intervention was effective in improving medication adherence relative to a standard of care control condition.
Few interventions for HIV treatment adherence have directly addressed the factors that correlate with nonadherence, such as depression and substance use. One exception has been intervening with social support to improve adherence. Simoni et al. (30) reported the outcomes of a peer support intervention aimed to increase HIV treatment adherence. The overall intervention effects were not significant. However, individuals with greater exposure to the supportive intervention did show greater signs of improvement in adherence as well as emotional adjustment. In another example of an intervention that targeted a correlate of nonadherence, Parsons et al. (31) tested a motivational intervention that directly addressed nonadherence among men and women who drink alcohol. The intervention demonstrated short-term improvements in adherence and health outcomes, but these benefits were short lived and were not accompanied by reductions in drinking. These studies suggested that it is possible to intervene with correlates of nonadherence and that interventions with greater intensity may have more marked and sustained effects.
Common Elements of Positive Prevention Interventions
Findings from two independent meta-analyses have indicated that the overall effects of 15 clinical trials have demonstrated significant reductions in HIV transmission risks among HIV- infected persons (32,33). All but one of the intervention trials indicated significant risk reduction. Crepaz et al. (32) found that risk reduction was demonstrated in interventions delivered in small group formats as well as individual counseling. Interventions with skills building components were more efficacious than those that did not explicitly train new skills. Interventions that articulated a specific theoretical foundation were more effective than those that were not grounded in theory. Interventions that were longer in duration were more efficacious than briefer interventions, although interventions that were based on ongoing service activities were not as effective. Johnson et al. (33) reported similar patterns in their findings. The two meta-analyses taken together lend strong support to both the short-term and longer-term effects of prevention interventions for people living with HIV/AIDS.
There are several advantages to targeting HIV prevention interventions to people living with HIV infection. Individuals who are known HIV positive are at definite risk for HIV transmission when they engage in unprotected intercourse with an uninfected partner. Unlike prevention approaches that target at-risk populations, which require reaching large numbers of individuals, reducing HIV transmission risk behaviors among a small number of people with known HIV infection can avert entire subepidemics. For example, Kalichman et al. (34) showed that a small group risk-reduction intervention for men and women living with HIV/AIDS resulted in lower HIV transmission rates from male participants to male and female uninfected partners compared with the control condition. Specifically, among HIV-positive men with uninfected male sex partners in the risk-reduction intervention group, the rate of HIV transmission at the 6-month follow-up was one fifth that of men in the control group. This public health benefit may generalize to other HIV prevention interventions that have similar effect sizes. Further mathematical modeling supports the population level impact of risk reduction among infected persons, where disclosing HIV status to sex partners by infected persons can reduce the risk of HIV transmission by as much as 40% (35).
Only one positive prevention intervention to date has directly addressed treatment adherence and risk behavior as well as coping and adjustment to living with HIV/AIDS. The Healthy Living intervention consisted of three intervention modules that were delivered in a case management-style series of counseling sessions (36). The three intervention components were based on Social Cognitive Theory—skills building approaches for coping and emotional adjustment, improving medication adherence, and reducing HIV transmission risks. The intervention demonstrated significant reductions in HIV transmission risk behaviors. However, the adherence and risk reduction components were not integrated and constituted separate sequential interventions. Despite their association and the common elements included in their respective interventions, trials of interventions that integrate both HIV treatment adherence and HIV risk reduction within a single model have not yet been completed.
Policy and Clinical Implications
The Centers for Disease Control and Prevention (1) has declared increased HIV testing to detect people infected with HIV and referral to care and prevention services the US national strategy for HIV prevention. Positive prevention is also emerging as an HIV prevention priority in developing countries and this movement is co-occurring with increased access to HIV treatments (2). Unfortunately, there are few evidence-based interventions that are available for use with people living with HIV and none that have integrated HIV treatment adherence with transmission risk reduction strategies.
The need for effective integrated interventions is therefore apparent. Currently, my research group is testing an integrated intervention model that simultaneously addresses HIV treatment adherence and HIV transmission risk reduction in people living with HIV/AIDS. The intervention is grounded in Social Cognitive Theory and aims to build skills for managing factors that correlate with both treatment nonadherence and HIV transmission risk behaviors. For example, the intervention addresses substance use, depression, and social support as they relate to nonadherence to medications and unsafe sex. The intervention uses parallel activities to increase medication-taking behaviors and reducing unprotected sex with uninfected and unknown HIV status partners. HIV-positive men and women attend small group sessions as well as individual counseling sessions at the start and the end of the groups. The intervention is being tested in a currently ongoing randomized trial.
Interventions that can simultaneously address HIV treatment adherence and risk behavior will fit the context of clinical care, which focuses on treatment and is increasingly expected to address prevention needs. Integrated interventions will also be cost efficient and may have synergistic effects for other health behaviors that are impeded by the same barriers—namely, substance use, depression, and social isolation. Given the immediate need and the current availability of evidence-based adherence and risk reduction interventions that share common elements, integrated strategies for enhancing adherence and reducing risks should be a public health and research priority.
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NOTES |
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This research was supported by Grant R01-MH71164 from the National Institute of Mental Health.
DOI:10.1097/PSY.0b013e3181773bce
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