| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
TREATMENT AND PREVENTIVE INTERVENTIONS |
From the Department of Medicine and the Institute of Human Virology of the University of Maryland School of Medicine, Baltimore, MD.
Address correspondence and reprint requests to Lydia R. Temoshok, Institute of Human Virology, University of Maryland School of Medicine, 725 W. Lombard Street, Rm. 146, Baltimore, MD 21201. E-mail: ltemoshok{at}ihv.umaryland.edu
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONNOTESREFERENCES |
|---|
Key Words: HIV secondary prevention • HIV prevention • HIV transmission • HIV infectiousness • biodisparity • sexually transmitted diseases
Abbreviations: AIDS = acquired immune deficiency syndrome; ART = antiretroviral therapy; CDC = Centers for Disease Control and Prevention; FDA = Food and Drug Administration; HIV = human immunodeficiency virus; HSV-2 = herpes simplex virus 2 (genital herpes); N-9 = Nonoxynol-9; PWP = prevention with positives; SAFE = Serostatus Approach to Fighting the Epidemic; STD = sexually transmitted disease.
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONNOTESREFERENCES |
|---|
In this paper, we argue that effective secondary prevention programs must go beyond the traditional prevention components of risk education, encouraging condom use, behavioral skills practice, and emotional support. Secondary prevention requires a broader approach, in which biomedically and epidemiologically informed behavioral interventions constitute an essential component of comprehensive, integrated, multidisciplinary HIV care. In concert with the objectives of CDC’s SAFE (3), we agree that effective secondary prevention programs should address a broad range of psychosocial needs (e.g., housing services, general mental health care). Expanding this mandate, we discuss recent findings from the biomedical sciences on viral and host factors that influence infectiousness to support the idea that the most proactive prevention programs will explicitly integrate biomedical interventions and approaches designed to reduce infectiousness, and thus, the sexual transmission of HIV. We also present our recommendations concerning areas whose importance to secondary prevention has not yet been fully recognized, where an expanded behavioral medicine interface is needed to enhance the efficacy of HIV secondary prevention.
Enhanced Adherence to Antiretroviral Treatment
Most prevention with positives (PWP) programs have focused on transmission risk behaviors, with limited attention to related risk-relevant behaviors, such as adherence to antiretroviral therapy (ART), which significantly affect transmission to uninfected sexual and needle-sharing partners. A higher viral load, as often found in suboptimally adherent patients, is associated with greater risk of HIV transmission (4), whereas patients in which HIV is well controlled by ART are less infectious (5). Adherence to ART has been associated with greater suppression of HIV in seminal plasma, although there are imperfect relationships among ART, reduced infectiousness, and reduced transmission risk (6). In general, however, suboptimally adherent HIV-infected persons can be assumed to transmit HIV more easily because of higher viral loads and increased concentrations of HIV in the genital tract.
Kalichman combined interventions that address both the objectives of increasing adherence to therapy and increasing the adoption and maintenance of HIV-STD risk reduction behaviors (7), as recommended in steps 4 and 5 of CDC’s SAFE strategy. Congruent with this perspective, we recommend integrating behavioral and biomedical approaches to reducing HIV infectiousness, which critically influences HIV transmission.
Transmission of Drug-Resistant HIV and Potential for Biodisparity
Numerous studies have shown that suboptimal adherence to HIV ART allows the selection and emergence of mutated and resistant isolates (8). Drug resistance constitutes a serious problem for the individual, leading to treatment failure, limited options for alternative treatments, and ultimately, disease progression. The significance of transmission of drug-resistant HIV to the spread of drug resistant virus has been debated, with some arguing that resistant HIV will represent only a small proportion of new infections in the future (9). A growing body of evidence suggests, however, that significant numbers of treatment-naïve patients—
20% of patients in some studies—have evidence of drug resistance and that a good portion of this resistance is to the best-tolerated and easiest-to-use drugs (10–12). One study of newly diagnosed and treatment-naïve patients in nine North American cities found that 16.5% had >10-fold resistance to at least one antiretroviral drug (13). European studies reported a range of 5% to 26% of treatment-naïve patients with drug-resistant virus (14). Smaller, but clinically significant, percentages of newly infected patients displayed phenotypic and genotypic resistance to multiple drugs, with estimates ranging from 1.2 to 10% of cases (13). Although the risk of new infections with drug-resistant virus has received the most attention, HIV-infected contacts of drug-resistant individuals are also at risk for "super infection" with drug-resistant viral isolates (15–17). Thus, existing data support the conclusion that transmission of resistant HIV is already a serious problem.
Transmission risk behaviors (e.g., unprotected intercourse, needle sharing) are not randomly distributed among HIV-infected individuals. Transmission risk behaviors occur commonly among those who know they are HIV positive (18,19) and are associated with complex psychosocial risk factors, which are also related to suboptimal adherence (7,20,21). Moreover, transmission risk behaviors and poor adherence are often correlated (22–24). For example, a recent study found that individuals who were less adherent to antiretroviral therapy (ART) were 46% more likely to engage in sexual transmission risk behaviors than were adherent patients (25).
Thus, there is evidence from a variety of sources suggesting that patients who are most likely to have drug-resistant HIV are also at increased risk of transmitting resistant HIV to others. This converging evidence suggests the possibility that multidrug-resistant HIV strains will spread within segregated sexual networks. To the extent that these sexual networks are characterized by differences in socioeconomic status, geography (e.g., socially isolated neighborhoods), HIV risk-relevant behaviors (e.g., injecting drug use, men having sex with men), and/or ethnicity/race, the result may be stratification of drug-resistant HIV into particular communities. If this happens, the currently observed social disparities in HIV outcomes resulting from socioeconomic difficulties and reduced access to health services may become biologically entrenched, as drug-resistant strains of HIV that are more difficult to treat appear more commonly in disadvantaged communities. We have coined the term "biodisparity" to refer to this biological entrenchment of social and economic disparities (26).
We have posited that biodisparities in drug-resistant HIV may become increasingly apparent among ethnic minorities (27). Epidemiological surveys reveal that HIV is distributed disproportionately across different age groups and races/ethnicities. One recent study reported that overall, HIV prevalence was 0.37% among persons aged 18 to 39 years and 0.54% in persons aged 40 to 49 years (28). However, among African-Americans, HIV prevalence was nearly 2% among males and 1% among females in those aged 18 to 39 years. Among persons aged 40 to 49 years, >4.5% of African-American males and nearly 3% of females were infected with HIV. African-Americans accounted for 50% of all AIDS cases reported in 2005 (28). We hypothesize that these ethnic/racial differences in the prevalence of HIV, combined with the differential spread of mutated and multidrug-resistant strains of the HIV virus within relatively distinct African-American communities, could work synergistically to increase dramatically HIV biodisparity in the US. In this potential scenario, options for treating African-Americans may become sharply diminished, as an increasing number of newly infected African-Americans will already have acquired resistance to the known HIV medications.
Amplified Transmission of HIV
Epidemiologists have long been aware of an apparent contradiction in HIV transmission data: the existence of a thriving heterosexually transmitted epidemic, despite the fact that the estimated likelihood of HIV transmission in a single heterosexual encounter is extremely low: 1 in 700 to 1 in 3000 for female-to-male vaginal transmission, and 1 in 200 to 1 in 2000 for male-to-female vaginal transmission (29). This apparent contradiction is accounted for by periods of amplified infectiousness (30), in which the risk of transmission per sexual encounter is many times higher than normal.
Acute HIV Infection
HIV-infected persons experience their highest levels of viral burden in the plasma shortly after infection, before the immune system has fully mounted its defenses (31). During the acute infection phase, the risk of vaginal transmission of HIV may be as high as 4% per coital act (32). Transmission risk per act of anal intercourse during the acute infection period is likely to be still higher, given that the baseline transmission risk, estimated at 1 in 10 to 1 in 1600, is much higher than for vaginal transmission (30).
It is, therefore, critical to develop strategies for identifying HIV infection early in the acute phase and to have systems in place for the rapid provision of medical treatment to reduce viral loads, behavioral assessments to identify transmission risk behaviors, and intensive prevention interventions to reduce enhanced transmission risk during the acute infection phase. A major problem is that patients with acute HIV infection are difficult to identify, as they either do not experience or do not pay attention to symptoms of acute infection. Primary care physicians, emergency room personnel, public health officials, social service providers, and other professionals who provide services to high-risk individuals should be educated about the symptoms of acute HIV infection. Testing strategies designed to identify acute HIV infection also show promise, particularly when they are combined with screening for risk behaviors associated with HIV acquisition, partner notification, and thorough and persistent contact tracing efforts (33).
Sexually Transmitted Diseases
The presence of "traditional" STDs, such as syphilis, gonorrhea, and genital herpes (herpes simplex virus 2 (HSV-2)) infection, increases both infectiousness and susceptibility to HIV (34–36). Although ulcerative STDs, such as HSV-2, syphilis, and chancroid, are associated with the greatest increase in HIV transmission risk (34,36,37), nonulcerative STDs also increase the likelihood of HIV transmission (36,38). In men with HIV, urethritis from Chlamydia or gonorrhea infection is associated with a higher seminal viral load (39). Treatment for those STDs lowers seminal viral load (40,41).
HSV-2 is perhaps the most significant STD involved in amplified HIV transmission risk, due to its wide prevalence and multiple biological interactions with HIV (42). In HIV-positive persons, HSV-2 infection increases expression of HIV in activated CD4+ cells and macrophages (43,44) and increases viral load (42,45), and HSV-2 lesions shed HIV directly (35,46). In HIV-negative persons, HSV-2 genital lesions represent points of entry for HIV, increasing susceptibility to infection. Moreover, during HSV-2 outbreaks, activated CD4+ cells migrate to the site of the lesion, providing a target-rich environment for HIV infection (35,47). These findings suggest that prompt diagnosis and treatment of STDs in both HIV-positive individuals and their HIV-negative partners are of critical importance to HIV prevention (48). It may be beneficial for HIV clinics to establish partner testing clinics in which full STD screening and treatment services are made available to partners, regardless of HIV status (48).
Seroconcordant Transmission Risk Behaviors
Most of the surveys on transmission risk behaviors among seropositive individuals, as well as intervention programs to change these behaviors, have focused on the risk of the HIV-positive person transmitting HIV to an uninfected person (someone known to be seronegative or serostatus unknown). Transmission risk behaviors among HIV-positive individuals vary according to partner serostatus, with the highest rates of unprotected intercourse occurring with partners known to be seropositive (49–52). Although such "serosorting" does decrease the likelihood of new HIV infections, it places HIV-positive individuals and their HIV-positive sex partners at greater risk of contracting additional STDs or other strains of HIV, and particularly poses a risk of superinfection with drug-resistant strains. Additionally, the acquisition of one or more STDs from a seroconcordant partner enhances HIV infectiousness in both partners, thus magnifying transmission risk for both to serodiscordant partners. Thus, seroconcordant transmission risk behaviors by persons with HIV also represent a significant public health danger, which has not been addressed in most PWP programs.
Sexual Dysfunction and HIV: Prevention Implications
Sexual dysfunction is common in both HIV-infected women (53,54) and men (54–59). In the HIV primary care clinic, male patients seeking treatment for sexual dysfunction represent a critical opportunity for secondary prevention. One study found that gay and bisexual men with erectile dysfunction had much higher rates of unprotected intercourse, presumably due to concerns about decreased sensation and erectile quality with condom use (59). Additionally, men seeking Viagra for recreational purposes reported significantly greater levels of risky sexual behaviors (60). Ostensibly seeking treatment for sexual dysfunction, these men may also present to HIV care providers. In the case of either legitimate erectile dysfunction or intended abuse of erectile dysfunction drugs, providers can presume that men seeking medications for erectile dysfunction are at greater risk of HIV transmission risk behaviors. Therefore, any request for these medications should prompt a referral for secondary prevention services.
Beyond Condoms: The Important Future Role of Microbicides in HIV Prevention
From the dawn of the HIV/AIDS epidemic in the early 1980s, condoms were promoted as the cornerstone of HIV behavioral prevention programs. The dangers of separating behavioral prevention programs from biomedical research on HIV are illustrated by the fact that latex condoms containing the microbicide detergent Nonoyxynol-9 (N-9) continued to be promoted by many programs long after a Phase III clinical trial published in a leading medical journal demonstrated that products containing N-9 may increase rather than decrease the risk of HIV transmission (61). Mechanisms posited for this increased transmission include vaginal irritation and ulceration, which degrade the protective barrier of the vaginal epithelium, allowing HIV to enter more easily (62) as well as causing vaginal inflammation that may enhance HIV infection by attracting HIV host cells to the vaginal mucosa and by activating HIV transcription in infected cells (63).
In recent years, there has been hope that a new generation of microbicides that preserve the body’s natural defenses might hold promise as providing durable protection against HIV that may be practical in terms of cost and ease of use (64). These hopes experienced a considerable setback with the recent early termination of two international Phase III trials of cellulose sulfate microbicides, after preliminary analyses revealed that the microbicide group had a higher rate of HIV transmission (65). To the extent that condom usage has a number of practical limitations, including social, religious, and cultural taboos, combined with the persistent observation that men often resist the proposed use of a condom by their sex partners (66), developing an effective vaginal microbicide to enable women to protect themselves without requiring the cooperation of their partners is a public health priority (64,67). As biomedical attempts to identify effective microbicides continue, behavioral scientists should work in concert with biomedical colleagues to understand and address potential attitudinal, knowledge, and practical barriers to their appropriate use.
Multidisciplinary Services and HIV Prevention
HIV risk behaviors are much more common among persons with mental illness (68–73) and active substance abusers (74–79). Additionally, increased levels of transmission risk behaviors are found among individuals with severe social needs, such as homelessness (68,80), domestic and/or intimate partner violence (81–83), and juvenile delinquency (78). These findings suggest that, rather than conceiving of HIV transmission risk as a specific behavioral problem requiring narrowly targeted services, it is important to recognize the role of a broad range of social, psychological, and medical services in promoting and enhancing HIV secondary prevention. Importantly, receiving treatment for mental illness was found to reduce transmission risk behaviors in active drug users (84). Housing programs, social work services, and general mental health care may all indirectly reduce transmission risk behaviors among HIV-positive individuals; thus, they represent critical components of HIV primary care.
Interventions Conducted by Medical Providers and/or in Healthcare Settings
Earlier Diagnosis of HIV Infection
The CDC’s revised testing recommendations issued in September 2006 (85), which advocate voluntary "opt out" HIV screening in healthcare settings and annual retesting of persons with known risk factors care, are important strategies toward the goal of increasing the number of infected persons who are aware of their HIV infection (28). Studies suggested that from 15% to 43% of HIV-positive individuals do not present for HIV testing until late in infection (86,87). In addition to the individual problems of higher mortality risk and less favorable response to treatment, late presentation means that opportunities to reduce transmission by reducing risky behaviors and/or infectivity have been missed. Many of the strategies to encourage earlier HIV diagnosis are most appropriate for acute healthcare settings. These include routine or opt-out HIV screening for individuals with diseases that share similar routes of transmission to HIV (STDs, viral hepatitis, drug addiction), those with signs of immune suppression (e.g., tuberculosis), and those in areas with high HIV incidence and or prevalence >0.1% (87). The use of rapid HIV tests, ideally with same-day confirmatory tests (which are, unfortunately, not yet available in the US), is advocated to reduce the percentage of tested individuals who do not return for their results and are lost from the healthcare system (88).
The CDC has recommended that all HIV-infected patients should be screened for behaviors associated with HIV transmission, questioned about symptoms of STDs, and tested initially and at least annually for laboratory evidence of certain STDs (syphilis, trichomoniasis for women, cervical chlamydial infection for sexually active and at-risk women) (85,89). STD screening and treatment have the potential to reduce HIV infectiousness in coinfected individuals. Moreover, questioning patients about transmission risks and STD symptoms offers HIV primary care providers a valuable opportunity to influence patients’ risk behaviors. Given their long-term relationships and frequent contacts with patients as well as their high level of perceived expertise in health matters, medical providers have a promising and cost-effective opportunity to deliver secondary prevention messages to very large numbers of HIV-positive individuals. Brief provider-based interventions may be especially beneficial in resource-limited settings in which skilled behavioral professionals are rare and practical barriers against intensive ongoing interventions exist.
It was reported that brief (3–5 minute) transmission risk messages delivered by medical providers at every nonurgent clinic visit resulted in a significant reduction in unprotected penetrative intercourse for those patients who had more than one sexual partner at baseline (90). Messages were more effective if they focused on the negative consequences of transmission risk behavior, rather than the positive consequences of protective behavior. The Options Project (91) provided a similar brief medical provider intervention, based on techniques of motivational interviewing, to 497 adult HIV patients in a primary HIV clinic setting. Remarkably, they found that, in the control arm of the study, rates of unprotected sex increased steadily over the study period. In contrast, rates of unprotected sex in the intervention arm decreased steadily during the study period. These findings suggest that not only are brief provider interventions beneficial in reducing the risk of HIV transmissions but providers’ failure to incorporate risk-reduction messages into ongoing primary care may have pernicious effects by providing patients with tacit messages that prevention is not important.
The responsibility for HIV prevention is commonly attributed to HIV-negative individuals (92), and persons with HIV who hold this perspective are more likely to engage in transmission risk behaviors (93). Universal provision of secondary prevention messages in HIV primary care clinics has the potential to enhance patients’ perceptions that they share in the responsibility for HIV prevention. Additionally, it is critical for HIV care providers to address misconceptions about relations among ART, transmission risk, and prevention responsibility to ensure that all HIV-positive individuals are aware that the reduced viral load associated with ART does not eliminate the risk of transmission (51,94).
Secondary Prevention Interventions Conducted by Behavioral Medicine Professionals
A meta-analysis of 12 randomized controlled trials of secondary prevention interventions found that effective interventions were guided by behavioral theory; delivered individually rather than in groups; delivered by professionals rather than peers; intensive and of long duration; and broadly focused on improving HIV-related coping and health factors, including medication adherence (95). Of particular note is that half of the interventions included in the meta-analysis had no significant effect. For example, the INSPIRE study, a large, well-designed, and theory-driven peer-based intervention for intravenous drug users failed to achieve a greater decrease in risk behaviors than an attention-and-group-support control (96).
These findings represent a strong caution to HIV service providers who are tempted to develop a local secondary prevention program by relying on intuitive models of behavior change and existing networks of peer counselors and paraprofessionals. Although such programs may attract community enthusiasm, they are unlikely to result in significant risk reduction among HIV-positive participants. Given the well-established difficulty of establishing and maintaining significant changes to sexual behaviors (97), interventions must be firmly grounded in behavioral theory and delivered by skilled clinicians. Additionally, because transmission risk behaviors involve complex interrelationships among behavioral, interpersonal, psychological, and biomedical factors, we believe that it is critically important that secondary prevention interventions be conducted by behavioral medicine professionals who have a strong grounding in the biomedical aspects of HIV, who are able to work closely with primary medical providers in the comprehensive management of individual patients.
Summary and Clinical/Policy Implications
The increase in ART rates worldwide has occurred in the context of widespread nonadherence (with concomitant drug resistance) and continuing transmission risk behaviors among infected individuals—particularly among those who are also nonadherent. Given these facts, if we cannot ensure a strategy to increase the number of patients with undetectable viremia and decrease the prevalence of transmission risk behaviors, there is a significant possibility that the transmission of resistant virus will increase. If ignored or left unchecked, these trends could contribute, inexorably, to the development of biodisparity—the biological entrenchment of existing psychosocial, behavioral, and systemic disparities—such that multidrug-resistant virus would be transmitted differentially within socioeconomically and/or ethnically distinct clusters or communities, severely limiting future HIV treatment options for these affected groups. In this paper, we have reviewed and recommended approaches to prevent this scenario. An important first step in this regard was recently announced by the CDC, which published an extension of its HIV Prevention Strategic Plan through 2010 (98). It includes, as part of the short-term Milestone 4, the modified objective of improving the capacity to monitor the transmission and prevalence of drug-resistant virus.
Documented high rates of transmission risk behaviors demonstrate the need for all HIV-positive persons to receive secondary prevention messages throughout the course of disease and treatment, and the importance of more intense and/or time-extended interventions for those among the HIV-positive population who do not change their risk behaviors based on short-term interventions. We must engage HIV-infected individuals in care and prevention from the point of diagnosis forward, constantly promoting the earliest possible diagnosis. There is clear evidence that patients who are engaged actively in their medical care are more likely to be adherent to their treatment programs (99,100). Positive engagement with the medical system is more likely if the foundations of patient-provider partnerships are laid during an infected individual’s first encounters with HIV counseling and testing programs. It is most efficient to implement HIV screening programs that are directly linked to comprehensive HIV primary care services, facilitating the transition from diagnosis to continuing care.
HIV-infected individuals in treatment represent the most promising target for initial intervention efforts because treatment relationships have already been established, and there is ample opportunity for assessment and amelioration of suboptimal adherence and transmission risk behavior (1,7,18). Behaviorally, we can intervene to address barriers to adherence such as maladaptive coping skills, substance use, suboptimal social support, and the variety of other factors that increase transmission risk behaviors. Additionally, we can provide comprehensive sexual health care in the context of HIV treatment, including monitoring and treating STDs and providing appropriate assessment and treatment of sexual dysfunction. Positive policy steps in these recommended directions are set forth in the new and modified objectives of the recently announced CDC HIV Prevention Strategic Plan, extended through 2010 (98): 1) integrating patient care delivery and prevention services, including adherence to treatment and partner notification services for persons diagnosed with HIV/AIDS; 2) increasing the proportion of persons newly diagnosed with HIV who are successfully linked to substance abuse treatment services, and social and mental health services, when needed; and 3) increasing the proportion of HIV care providers offering routine, periodic STD screening and treatment to HIV-infected clients.
Behavioral intervention programs must be established as a fully integrated component of HIV primary care, addressing the correlated objectives of adherence promotion and secondary prevention. Building on the sound conceptual framework of CDC’s SAFE (3) and the newly revised CDC HIV Prevention Strategic Plan, extended through 2010 (98), effective prevention programs should consist of multidimensional biomedical and behavioral approaches to reduce HIV infectiousness, drug resistance, and transmission.
|
NOTES |
|---|
|
TOPABSTRACTINTRODUCTIONNOTESREFERENCES |
|---|
Support by Department of Health and Mental Hygiene contract, "Integrating HIV Prevention into Primary Care Settings Serving HIV Positive Individuals" (L.T.), contributed to both authors’ knowledge and experience relevant to preparing this paper. This paper is dedicated to our friend and colleague Awilda Mendez-Muniz, whose journey back to health has been so inspiring and for which we hope the return is swift and complete.
DOI:10.1097/PSY.0b013e31817739b4
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONNOTESREFERENCES |
|---|
This article has been cited by other articles:
 |
|
 |
|
  J. Leserman and L. R. Temoshok A Road Well Traveled (Although Not Yet a Super Highway) Psychosom Med, June 1, 2008; 70(5): 521 - 522. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
