Adherence to antiretroviral therapies (ART) is the strongest predictor of viral suppression among individuals infected with HIV, however, limited data exists to understand the patterns of adherence that confer the greatest benefit across different ART regimens.
Longitudinal data pooled from 16 studies conducted between 1997 and 2009 across the United States.
Adherence was measured using Medication Event Monitoring System. Percentage of time with sufficient drug concentrations (covered time) and the length of the longest treatment interruption during the 28 days prior to plasma HIV-RNA measurements were calculated. Logistic regression with generalized estimating equations was used to estimate medication-specific adherence estimates on detectable HIV-RNA (>400 copies/ml).
One thousand and eighty-eight participants with 3795 HIV-RNA measures were studied. Both lower covered time and greater longest interruption showed dose– response relationships with the odds of detectable HIV-RNA; however, estimates did not vary by medication regimen. Compared with 93–100% coverage, periods of 0–25% covered time had a three-fold increased risk of detectable HIV-RNA [odds ratio (OR)=3.22, 95% confidence interval (CI): 2.48–4.19]. Similarly, compared to longest interruptions of 0–48 h, longest interruptions of 21–28 days had a nearly four-fold increased risk of detectable HIV-RNA (OR=3.65, 95% CI: 2.77, 4.81).
We found that adherence was consistently strongly associated with treatment response across ART regimens. Of the patterns of adherence, longer interruptions may have greater impact than covered time. Future research should investigate additional methods for examining adherence patterns, understanding the determinants of consecutive missed doses and the evaluation of interventions designed to address interruptions in treatment.
antiretroviral therapy; medication adherence; protease inhibitors; reverse transcriptase inhibitors; viral load
Efforts to scale-up HIV care and treatment have been successful at initiating large numbers of patients onto antiretroviral therapy (ART), although persistent challenges remain to optimizing scale-up effectiveness in both resource-rich and resource-limited settings. Among the most important are very high rates of ART initiation in the advanced stages of HIV disease, which in turn drive morbidity, mortality, and onward transmission of HIV. With a focus on sub-Saharan Africa, this review article presents a conceptual framework for a broader discussion of the persistent problem of late ART initiation, including a need for more focus on the upstream precursors (late HIV diagnosis and late enrollment into HIV care) and their determinants. Without additional research and identification of multilevel interventions that successfully promote earlier initiation of ART, the problem of late ART initiation will persist, significantly undermining the long-term impact of HIV care scale-up on reducing mortality and controlling the HIV epidemic.
Late ART initiation; sub-Saharan Africa; scale-up; conceptual framework; retention
Minority race/ethnicity is generally associated with antiretroviral therapy nonadherence in US-based studies. Limitations of the existing literature include small samples, subjective adherence measures, and inadequate control for potential confounders such as mental health and substance use, which have been consistently associated with poorer adherence.
Individual-level data were pooled from 13 US-based studies employing electronic drug monitoring to assess adherence. Adherence was operationalized as percent of prescribed doses taken from the first 12 (monthly) waves of data in each study. Depression symptoms were aggregated from several widely used assessments, and substance use was operationalized as any use of cocaine/stimulants, heroin/opiates, ecstasy, hallucinogens, or sedatives in the 30–365 days preceding baseline.
The final analytic sample of 1809 participants ranged in age from 18 to 72 years and was 67% male. Participants were 53% African American, 14% Latino, and 34% White. In a logistic regression adjusting for age, gender, income, education, and site, race/ethnicity was significantly associated with adherence (P < 0.001) and persisted in a model that also controlled for depression and substance use (P < 0.001), with African Americans having significantly lower adherence than Latinos [odds ratio (OR) = 0.72, P = 0.04] and whites (OR = 0.60, P < 0.001). Adherence did not differ between whites and Latinos (OR = 0.84, P = 0.27).
Racial/ethnic differences in demographics, depression, and substance abuse do not explain the lower level of antiretroviral therapy adherence in African Americans observed in our sample. Further research is needed to explain the persistent disparity and might examine factors such as mistrust of providers, health literacy, and inequities in the health care system.
HIV/AIDS; race/ethnicity; antiretroviral treatment; medication adherence
In the era of anti-retroviral therapy (ART), depression and substance use predict hastened HIV disease progression but the underlying biological or behavioral mechanisms that explain these effects are not fully understood.
Using outcome data from 603 participants enrolled in a randomized controlled trial of a behavioral intervention, binary logistic and linear regression were employed to examine whether inconsistent patterns of ART utilization partially mediated the effects of depression and substance use on higher HIV viral load over a 25-month follow-up.
Elevated affective symptoms of depression independently predicted ART discontinuation (Adjusted OR [AOR] = 1.39, 95% CI = 1.08 – 1.78), and use of stimulants at least weekly independently predicted intermittent ART utilization (AOR = 2.62, 95% CI = 1.45 – 4.73). After controlling for the average self-reported percentage of ART doses taken and baseline T-helper (CD4+) count, elevated depressive symptoms predicted a 50% higher mean viral load, and weekly stimulant use predicted a 137% higher mean viral load. These effects became non-significant after accounting for inconsistent patterns of ART utilization, providing evidence of partial mediation.
Inconsistent patterns of ART utilization may partially explain the effects of depression and stimulant use on hastened HIV disease progression.
Access; Adherence; Antiretroviral; Cocaine; Depression; Disease Progression; Highly Active; HIV/AIDS; HIV Viral Load; Methamphetamine; Substance Use; Utilization
Opiate substitution treatment has been associated with better adherence to lifesaving antiretroviral medications, but the impact of other substance abuse treatment on adherence is unknown.
In this study, 215 patients who had been in adherence-focused research studies provided electronically-measured adherence data and a measure of whether the patient had recently been in substance abuse treatment. Recent engagement in substance abuse treatment was independently associated with significantly higher adherence, after covarying for recent substance use and other factors potentially affecting adherence.
The findings suggest that substance abuse treatment is associated with better adherence. Potential mechanisms by which substance abuse treatment improves adherence, such as more stability or more future-orientation, require further study.
Medication adherence; AIDS; Substance abuse; Treatment
There is an urgent need for valid, reliable, and simple-to-use screening tools for HIV-associated dementia (HAD) in South Africa, as little is known about its impact on South Africa's 5.5 million people living with HIV (PLWH). Screening for HAD in South Africa involves several challenges, including few culturally appropriate and validated screening tools, and a shortage of trained personnel to conduct screening. This study examined rates of positive HAD screens as determined by the cutoff score on the International HIV Dementia Scale (IHDS) administered by nonspecialist community health workers (CHWs) in South Africa and examined associations between positive HAD screens and common risk factors for HAD. Sixty-five Xhosa-speaking HIV-positive individuals on antiretroviral therapy (ART) with low CD4 counts and documented ART adherence problems were administered a battery of demographic, psychiatric and neurocognitive screening measures. Positive HAD screens were present in 80% of the sample. Presence of a current alcohol dependence disorder and CD4 counts of 200 or lower were significantly associated with positive HAD screens. HIV-positive South Africans on ART with low CD4 counts and ART adherence problems may be at a very high risk for HAD, highlighting the need for more routine screening and monitoring of neurocognitive functions among South Africa's millions of PLWH on ART. Future research is needed to: (1) validate IHDS performance against a gold standard neurocognitive battery for the detection of HAD among larger samples of Xhosa-speaking South Africans with ART adherence difficulties and (2) compare performance of CHW to expert health care personnel in administering the IHDS.
Unprotected sexual intercourse remains a primary mode of HIV transmission in the United States. We found that receipt of services to reduce HIV transmission-risk behaviors was low among 3787 HIV-infected individuals and that men who have sex with men were especially unlikely to receive these services even though they were more likely to report unprotected sexual intercourse with seronegative and unknown serostatus casual partners. Greater efforts should be made to ensure that prevention counseling is delivered to all HIV-infected persons, especially men who have sex with men.
An ethnically diverse sample of 120 mostly gay-identified men who engaged in “bareback” intercourse was recruited via the Internet in New York City. By study design three quarters of participants were HIV-uninfected and engaged in condomless receptive anal intercourse. In the course of face-to-face in-depth interviews, participants were asked what led them to have their first bareback experience as well as to continue with the behavior. Qualitative analysis identified the pivotal role that sexual pleasure and intimacy have in this population and how drives for sexual satisfaction, adventure, intimacy, and love overpower health concerns and condom use recommendations. Men interested in bareback sex use a variety of defense mechanisms to account for, justify, and exonerate their behavior. HIV-prevention interventions have paid insufficient attention to libidinal drives, a crucial element of psychological functioning.
bareback; gay; homosexual; risk
Adherence to antiretroviral therapy (ART) is integral to the successful treatment of HIV infection. Research has indicated that HIV-infected Latinos may have difficulty adhering to ART. While studies have demonstrated strong relationships between numerous psychosocial factors and ART adherence, no research has examined if cultural factors are also involved in ART adherence among Latinos. Our study examined the relationship between acculturation to mainstream U.S. culture, bicultural self-efficacy, and ART adherence among HIV-infected Puerto Rican adults living in the United States. Participants with ≥ 95% adherence scored higher on U.S.- and Latino-involvement acculturation scales and on a measure of bicultural self-efficacy compared to those with suboptimal adherence. Among bicultural HIV-infected Puerto Ricans both acculturation and self-efficacy to navigate between cultures were positively related to adherence. Understanding the role of an individual’s sociocultural experience may help elucidate why HIV-infected Latinos have difficulties achieving optimal ART adherence and improve ART adherence interventions.
acculturation; adherence; antiretroviral; bicultural; Hispanic; HIV; Latino; Puerto Rican; self-efficacy
Depression consistently predicts nonadherence to human immunodeficiency virus (HIV) antiretroviral therapy, but which aspects of depression are most influential is unknown. Such knowledge could inform assessments of adherence readiness and the type of depression treatment to utilize.
We examined how depression severity, symptom type and change over time relate to adherence.
Microelectronic adherence and self-reported depression data from 1374 participants across merged studies were examined with cross-sectional and longitudinal analyses. Depression variables included a continuous measure, categorical measure of severity, cognitive and vegetative subscales, and individual symptoms.
At baseline, mean adherence was 69%, and 25% had mild/moderate and 18% had severe depression. In cross-sectional multivariate analyses, continuous depression, cognitive depressive symptoms and severe depression were associated with lower adherence. In longitudinal analysis, reductions in both continuous and categorical depression predicted increased adherence.
The relationship between global continuous depression and nonadherence was statistically significant, but relatively weak compared to that of cognitive depressive symptoms and severe depression, which appear to pose strong challenges to adherence and call for the need for early detection and treatment of depression.
depression; cognitive depressive symptoms; HIV/AIDS; antiretroviral adherence
The integration of original data from multiple antiretroviral (ARV)
adherence studies offers a promising, but little used method to generate
evidence to advance the field. This paper provides an overview of the design and
implementation of MACH14, a collaborative, multi-site study in which a large
data system has been created for integrated analyses by pooling original data
from 16 longitudinal ARV adherence studies. Studies selected met specific
criteria including similar research design and data domains such as adherence
measured with medication event monitoring system, psychosocial factors related
to adherence behavior, and virologic and clinical outcomes. The data system
created contains individual data (collected between 1997 and 2009) from 2,860
HIV patients. Collaboration helped resolve the challenges inherent in pooling
data across multiple studies, yet produced a data system with strong statistical
power and potentially greater capacity to address key scientific questions than
possible with single-sample studies or even meta-analytic designs.
HIV/AIDS; Adherence; MEMS Multi-site Antiretroviral medication; Individual participant data
Relationships between mental health symptoms (anxiety and depression) or a positive state of mind and behavior associated with HIV transmission (substance use and risky sexual behavior) were explored in a longitudinal study on persons living with HIV (PLH; n = 936) who were participants in a transmission-prevention trial. Bivariate longitudinal regressions were used to estimate the correlations between mental health symptoms and HIV-related transmission acts for three time frames: at the baseline interview; over 25 months; and from assessment to assessment. At baseline, mental health symptoms were associated with transmission acts. Elevated levels of mental health symptoms at baseline were associated with decreasing alcohol or marijuana use over 25 months. Over 25 months, an increasingly positive state of mind was associated with decreasing alcohol or marijuana use; an increasingly positive state of mind in the immediate condition and increasing depressive symptoms in the lagged condition were related to increasing risky sexual behavior. Our findings suggest that mental health symptoms precede a decrease in substance use and challenge self-medication theories. Changes in mental health symptoms and sexual behavior occur more in tandem.
HIV; Mental Health; Depression; Anxiety; Substance Abuse; Sexual behavior
Acute/early HIV infection is a period of high risk for HIV transmission. Better understanding of behavioral aspects during this period could improve interventions to limit further transmission. Thirty-four participants with acute/early HIV infection from six U.S. cities were assessed with the Mini International Diagnostic Interview, Beck Depression Inventory II, State-Trait Anxiety Inventory, Brief COPE, and an in-depth interview. Most had a pre-HIV history of alcohol or substance use disorder (85%); a majority (53%) had a history of major depressive or bipolar disorder. However, post-diagnosis coping was predominantly adaptive, with only mild to moderate elevations of anxious or depressive mood. Respondents described challenges managing HIV in tandem with pre-existing substance abuse problems, depression, and anxiety. Integration into medical and community services was associated with adaptive coping. The psychiatric context of acute/early HIV infection may be a precursor to infection, but not necessarily a barrier to intervention to reduce forward transmission of HIV among persons newly infected.
Acute HIV infection; psychiatric disorder; substance use disorder; coping
Risk reductions behaviors are especially important during acute/early HIV infection, a period of high transmission risk. We examined how sexual behaviors changed following diagnosis of acute/early HIV infection. Twenty-eight individuals completed structured surveys and in-depth interviews shortly after learning of their infection and two months later. Quantitative analyses revealed significant changes after diagnosis, including reductions in total partners and decreases in the proportion of unprotected sex acts occurring with uninfected partners (serosorting). Qualitative findings indicated that these changes were motivated by concerns about infecting others. However, participants were less successful at increasing the frequency with which they used condoms. These results suggest that the initial diagnosis with HIV may constitute an important component of interventions to promote risk reduction during the acute/early stages of the disease.
acute HIV; serosorting; behavior change; HIV prevention
Acute/early HIV infection plays a critical role in onward HIV transmission. Detection of HIV infections during this period provides an important early opportunity to offer interventions which may prevent further transmission. In six U.S. cities, persons with acute/early HIV infection were identified using either HIV RNA testing of pooled sera from persons screened HIV antibody negative or through clinical referral of persons with acute or early infections. Fifty-one cases were identified and 34 (68%) were enrolled into the study; 28 (82%) were acute infections and 6 (18%) were early infections. Of those enrolled, 13 (38 %) were identified through HIV pooled testing of 7,633 HIV antibody negative sera and 21 (62%) through referral. Both strategies identified cases that would have been missed under current HIV testing and counseling protocols. Efforts to identify newly infected persons should target specific populations and geographic areas based on knowledge of the local epidemiology of incident infections.
Acute HIV infection; nucleic acid amplification tests; HIV RNA testing; early detection of acute HIV infection
Acute/early HIV infection is a period of high HIV transmission. Consequently, early detection of HIV infection and targeted HIV prevention could prevent a significant proportion of new transmissions. As part of an NIMH-funded multisite study, we used in-depth interviews to explore understandings of acute HIV infection (AHI) among 34 individuals diagnosed with acute/early HIV infection in six U.S. cities. We found a marked lack of awareness of AHI-related acute retroviral symptoms and a lack of clarity about AHI testing methods. Most participants knew little about the meaning and/or consequences of AHI, particularly that it is a period of elevated infectiousness. Over time and after the acute stage of infection, many participants acquired understanding of AHI from varied sources, including the Internet, HIV-infected friends, and health clinic employees. There is a need to promote targeted education about AHI to reduce the rapid spread of HIV associated with acute/early infection within communities at risk for HIV.
HIV/AIDS; Awareness; Acute HIV; HIV prevention
Acute/early HIV infection is a period of heightened HIV transmission and a window of opportunity for intervention to prevent onward disease transmission. The NIMH Multisite Acute HIV Infection (AHI) Study was an exploratory initiative aimed at determining the feasibility of recruiting persons with AHI into research, assessing their psychosocial and behavioral characteristics, and examining short-term changes in these characteristics. This paper reports on lessons learned in the study, including: (1) the need to establish the cost-effectiveness of AHI testing; (2) challenges to identifying persons with AHI; (3) the need to increase awareness of acute-phase HIV transmission risks; (4) determining the goals of behavioral interventions following AHI diagnosis; and (5) the need for “rapid response” public health systems that can move quickly enough to intervene while persons are still in the AHI stage. There are untapped opportunities for behavioral and medical science collaborations in these areas that could reduce the incidence of HIV infection.
Acute HIV infection; HIV prevention; Public health
Relatively little is known about sexual dysfunction (SD) in men who have sex with men (MSM).
In order to better understand SD symptoms in MSM, we assessed self-reported SD symptoms, individually and by latent class analysis (LCA).
In 2004–2005 an Internet sample of U.S. MSM was recruited from gay-oriented sexual networking, chat and news websites. The analytic sample comprised 7,001 men aged 18 or older who reported lifetime male sex partners and oral or anal sex with a male partner in their most recent encounter within the past year.
Main Outcome Measures
Seven questions on SD symptoms that occurred during the past 12 months inquired about low sexual desire, erection problems, inability to achieve an orgasm, performance anxiety, premature ejaculation, pain during sex, and sex not being pleasurable.
Self-reported symptoms of SD were high. Overall, 79% of men reported one or more SD symptoms in the past year, with low sexual desire, erection problems, and performance anxiety being the most prevalent. Four distinct underlying patterns of sexual functioning were identified by LCA: no/low SD, erection problems/performance anxiety, low desire/pleasure, and high SD/sexual pain. High SD/sexual pain was distinguished from the other patterns by club drug use and use of prescription and non-prescription erectile dysfunction medication before sex in the past year. Additionally, men associated with the high SD/sexual pain group were younger, single, more likely to have poor mental and physical health, and more likely to have been diagnosed with a sexually transmitted infection in the past year compared to men in the no/low SD group.
LCA enabled us to identify underlying patterns of sexual functioning among this sample of MSM recruited online. Future research should investigate these distinct subgroups with SD symptoms in order to develop tailored treatments and counseling for SD.
Male Sexual Dysfunction; Men Who Have Sex with Men; Internet; Gay Men
Although some rectal douches result in surface epithelium loss and potential increase of HIV transmission, men who have sex with men (MSM) continue to use them. We describe the prevalence of this practice among MSM engaging in unprotected receptive anal intercourse (URAI) in risky circumstances. A multiethnic sample with overrepresentation of HIV-negative MSM who had URAI in the previous year was recruited exclusively through the Internet. Participants were 105 MSM (78 HIV-negative, 27 HIV-positive). 53% of HIV-negative and 96% of HIV-positive men douched in preparation for sex, most of them frequently or always, mainly for hygienic purposes. 27% of HIV-negative and 44% of HIV-positive douched after sex, partly believing douching protected from infections. Douching practices started around age 25. Regression analyses found the association between HIV status and douching occasions persisted after controlling for demographic characteristics and number of URAI occasions. Rectal douching in preparation for sex is common among men who practice URAI. This population could benefit from alternatives to condoms, such as rectal microbicides. Given the popularity of pre-coital douching and its frequency, a harmless rectal douche that could deliver a rectal microbicide could have great acceptability.
receptive anal sex; douching; homosexual; gay; enema
Although stigma is considered a major barrier to effective responses to the HIV/AIDS epidemic, stigma reduction efforts are relegated to the bottom of AIDS program priorities. The complexity of HIV/AIDS related stigma is often cited as a primary reason for the limited response to this pervasive phenomenon. In this paper, we systematically review the scientific literature on HIV/AIDS related stigma to document the current state of research, identify gaps in the available evidence, and highlight promising strategies to address stigma. We focus on the following key challenges: defining, measuring, and reducing HIV/AIDS related stigma as well as assessing the impact of stigma on the effectiveness of HIV prevention and treatment programs. Based on the literature, we conclude by offering a set of recommendations that may represent important next steps in a multifaceted response to stigma in the HIV/AIDS epidemic.
HIV; AIDS; stigma; discrimination; systematic review
Disparities in the use of antiretroviral therapy (ART) for HIV disease have been documented across race, gender, and substance use groups.
The current analysis compares self-reported reasons for never taking or stopping ART among a diverse sample of men and women living with HIV.
HIV + (N = 3,818) adults, 968 of whom reported discontinuing or never using ART.
Computerized self-administered and interviewer-administered self-reported demographic and treatment variables, including gender, race, ethnicity, CD4 count, detectable viral load, and reported reasons for not taking antiretroviral therapy.
Despite equivalent use of ART in the current sample, African-American respondents were 1.7 times more likely to report wanting to hide their HIV status and 1.7 times more likely to report a change in doctors/clinics as reasons for stopping ART (p = .049, and p = .042) and had odds 4.5 times those of non-African Americans of reporting waiting for viral marker counts to worsen (p = < .0001). There was a lower tendency (OR = 0.4) for women to endorse concerns of keeping their HIV status hidden as a reason for stopping ART compared to men (p = .003). Although those with an IDU history were less likely to be on ART, no differences in reasons for stopping or never initiating ART were found between those with and without an IDU history.
A desire to conceal HIV status as well as a change in doctors/clinics as reasons for discontinuing ART were considerably more common among African Americans, suggesting that perceived HIV/AIDS stigma is an obstacle to maintenance of treatment. Findings also indicate differences in reasons for stopping ART by gender and a perceived desire to wait for counts to worsen as a reason for not taking ART by African Americans, regardless of detectable viral load, CD4 count, age, education, employment, sexual orientation, and site.
HIV/AIDS; treatment disparities; gender; race; ethnicity; substance use
Data on intentional condomless anal intercourse in risky contexts, also known as “barebacking,” among ethnic minority MSM, whose rates of HIV infection continue to rise, is extremely limited. In this study, thirty-one Latino MSM who seek barebacking partners via the Internet underwent in-depth interviews about bareback sex and its association to pleasure, substance use, HIV concerns, and cultural identity. Participants reported engaging in bareback sex due to the physical and emotional pleasure they experience. They expressed concern about HIV infection and took steps to reduce risk of infection. While a majority of participants reported using alcohol or drugs in the context of bareback sex, substance use did not appear to propel the behavior. Crystal methamphetamine use, prevalent only among our HIV-positive participants, was related to very high HIV-risk behavior. In this sample, culture did not seem to play a large role in barebacking.
HIV Prevention; Condoms; Latino; Gay