Although the mortality rate among HIV-positive persons declined markedly in the era of highly active antiretroviral therapy (HAART), HIV-related health disparities have been observed in various groups including the urban poor [1–5]. Structural factors like unstable housing are linked to hastened mortality among individuals living with AIDS , but the mortality rate among homeless and marginally housed HIV-positive persons is substantially attenuated among those that consistently utilize HAART . Homeless or marginally housed persons experience difficulties with accessing and utilizing healthcare services, which contributes to the more rapid progression of prevalent infectious diseases such as HIV/AIDS . Difficulties with engaging in healthcare and utilizing HAART represent a lost opportunity for reducing community HIV viral load, which has been linked to HIV incidence [9,10].
The structural barriers that HIV-positive impoverished persons encounter to accessing and utilizing HIV medical care may be further exacerbated by comorbid mental health and substance use disorders. Prior research examining the implications of psychiatric comorbidities for HIV disease management has focused extensively on individuals engaged in HIV medical care. Cross-sectional studies with participants enrolled in HIV medical clinics observed that co-occurring mental health disorders and substance use as well as substance use alone were associated with decreased odds of HAART utilization [11,12]. Among those on HAART, co-occurring mental health and substance use disorders as well as substance use disorders alone were associated with decreased odds of HIV viral suppression . In contrast, Himelhoch et al.  report divergent findings in two HIV clinic-based cohort studies. One investigation observed that the odds of discontinuing HAART in the 2 years following initiation were lower among those with a severe mental illness (SMI) or a depressive disorder . The other indicated that those with a psychiatric disorder (i.e. any mental health or substance use disorder) were more likely to initiate HAART, had greater odds of remaining on HAART for at least 6 months, and were 40% more likely to survive . Because studies conducted with HIV clinic-based samples utilized chart review to assess psychiatric diagnoses [11–14], it is difficult to disentangle the effect of the psychiatric diagnosis from the receipt of integrated treatment that often included psychiatric care . In contrast, studies that recruited HIV-positive persons from the community have consistently observed that depression and substance use are linked to impaired HAART utilization and higher HIV viral load [16–18]. It is noteworthy, however, that community-recruited, HIV-positive cohorts have relied on self-report measures of depression and substance use that did not screen other relevant psychiatric diagnoses (e.g. psychotic spectrum disorders and bipolar I/II disorders) that could be associated with HAART utilization and viral load. The present study administered a well validated screening measure for psychiatric disorders to a sample of community-recruited, HIV-positive impoverished persons in order to examine whether specific mental health and substance use disorders were differentially associated with HAART utilization and HIV viral load. We hypothesized that mental health and substance use disorders would be associated with decreased odds of HAART utilization and elevated HIV viral load after controlling for demographic and structural factors.
From July 2004 to May 2006, a mobile outreach team recruited a sample of homeless and marginally housed adults from San Francisco homeless shelters, free food programs, and a probability sample of low-income hotels where the probability of selection was proportional to the number of hotel residents . All individuals who tested HIV-positive were invited to participate in a study visit that included an interviewer-administered questionnaire assessing demographic and structural factors as well as self-reported HIV regimen. At this study visit, participants also completed a computerized Diagnostic Interview Schedule (DIS) to screen for psychiatric disorders. Peripheral venous blood samples were obtained during separately scheduled, quarterly visits to a community field site. All participants provided blood samples within 90 days of the study visit that included the computerized DIS (median = 22 days).
Demographic and structural factors
Demographic and structural factors included sex, ethnicity, age, education, income, percentage of income from subsidizes, current insurance status, enrollment in the California AIDS Drug Assistance Program (ADAP; established in 1987 to help ensure that HIV-positive uninsured and under-insured individuals have access to medication), nights spent on the street, and nights spent in a shelter were assessed.
Self-reported utilization of mental health and substance abuse treatment
Utilization of mental health treatment included any outpatient or inpatient services during the past 90 days. Utilization of substance abuse treatment included any outpatient or residential services, detoxification, or 12-step self-help group attendance during the past 90 days.
Computerized Diagnostic Interview Schedule
The computerized DIS is a reliable and valid measure that screens for current mental health and substance use disorders [20,21]. The computerized DIS was administered to determine whether participants reported symptoms consistent with a current major depressive episode; diagnosis of post-traumatic stress disorder (PTSD); SMI (i.e. manic/hypomanic episode – bipolar I/II disorders or schizophrenia); alcohol use disorder; opiate use disorder; and stimulant (i.e. cocaine or amphetamines) use disorder.
Regimens were classified as HAART if they included at least three antiretroviral medications in which one medication was a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor. Individuals using any other regimen were classified as not on HAART.
HIV disease markers
HIV-1 viral load was determined using the AMPLICOR ultrasensitive method for the in-vitro reverse transcriptase polymerase chain reaction (RT-PCR) assay (Roche Laboratories, US # 83088), which has a valid range of 50–750 000 copies/ml. T-helper (CD4+) count was determined using direct immunoflourescence.
Individuals on HAART (n = 154) were compared to a reference group that was eligible for HAART (i.e. CD4+ cell count <350 cells/μl) based on the World Health Organization (WHO) guidelines at the time of the study  but not currently taking it (n = 73). Using multiple logistic regression, the adjusted odds ratio (AOR) reflects the independent association of each variable with HAART utilization, controlling for all other variables in the model. Similarly, independent correlates of log10 HIV viral load were examined using multiple linear regression among participants that were on HAART and had viral load data available (n = 147). Using a simple formula [100(10Beta–1)], unstandardized parameter estimates were converted to determine the percentage increase in mean viral load that was associated with each significant correlate. Because HAART adherence is in the causal pathway between psychiatric factors and viral load, it was not included in current analyses.
The mean age of the 227 participants included in these analyses was 42 years (range 27–66). Most participants were men (68%); 40% were Caucasian, 47% were African American, and 13% were other ethnic minorities; 71% completed high school. Thirty-four percent of participants had an undetectable HIV viral load and the mean CD4+ cell count was 351 (SD = 268) cells/μl. Of the 157 participants currently taking antiretroviral medications, 98% (n = 154) were on HAART regimens and half (52%) of those on HAART had an undetectable viral load. Using the DIS, estimated prevalence of the following current psychiatric disorders was 31% for a major depression episode, 17% for PTSD, 15% for a SMI [of which 14% reported hypomanic episode(s); 77% manic episode(s); 9% symptoms consistent with schizophrenia], 8% for an alcohol use disorder, 8% for an opiate use disorder, and 32% for a stimulant use disorder. Taken together, 56% of participants screened positive for at least one current mental health or substance use disorder.
Correlates of HAART utilization
As shown in Table 1, being enrolled in ADAP (82 vs. 64%) and receipt of any mental health treatment in the past 90 days (82 vs. 62%) were associated with more than three times greater odds of HAART utilization. Having slept on the street in the past 90 days was associated with substantially lower odds of HAART utilization (22 vs. 72%). Independent of these demographic and structural factors, screening positive for a stimulant use disorder was associated with substantially lower odds of HAART utilization (53 vs. 75%).
Correlates of HIV viral load among those on HAART
As shown in Table 2, compared to Caucasian participants, African American (2.20 vs. 2.65 log10 copies/ml) and other ethnic minority (1.79 vs. 2.65 log10 copies/ml) individuals had a significantly lower viral load. After controlling for demographic and structural factors, screening positive for a SMI was associated with a six times higher viral load (3.00 vs. 2.22 log10 copies/ml).
To our knowledge, this study is among the first to observe that specific mental health and substance use disorders are differentially associated with HAART utilization and HIV viral load. Building on prior research which observed that stimulant users experience difficulties with HIV disease management [5,18,23], screening positive for a stimulant use disorder was independently associated with impaired HAART utilization after controlling for demographic and structural factors as well as other comorbid psychiatric disorders. Findings also indicated that receipt of mental health treatment was independently associated with enhanced HAART utilization, which is consistent with previous studies [13,16,24]. In contrast to previous research [18,25–28], the present study did not observe that screening positive for a stimulant use disorder was associated with elevated HIV viral load among those on HAART. It is noteworthy, however, that screening positive for a SMI was independently associated with a six times higher HIV viral load. There is growing recognition that substance users often experience co-occurring social, structural and psychiatric barriers to HAART adherence . Findings from the present investigation indicate that the presence of a SMI is an important barrier to reducing viral load among HIV-positive impoverished persons. Taken together, it appears that structural and psychiatric barriers compromise HIV treatment success, even in a resource-rich environment in which integrated care and antiretroviral medications are more accessible than most areas of the world.
Although the present cross-sectional investigation provides some of the first data regarding the association between specific psychiatric diagnoses and HIV disease management, longitudinal studies are needed to examine whether and how specific psychiatric diagnoses independently predict more rapid HIV disease progression. Further research is also needed to replicate these findings and determine if impaired HAART adherence mediates the association between SMI and elevated HIV viral load.
Irrespective of whether elevated viral load among those with SMI is due to stress-induced immune suppression, impaired HAART adherence or other mechanisms, findings from this study have important clinical implications. Adjuvant interventions that address social and structural barriers as well as target prevalent psychiatric comorbidities in this population could promote HAART utilization and reduce viral load among HIV-positive impoverished persons. Optimizing individual-level health outcomes among HIV-positive impoverished persons may lead to greater reductions in community HIV viral load, which is critical to the success of ‘test and treat’ approaches to HIV prevention .
A.W.C. developed study hypotheses and was the primary individual responsible for data analysis and manuscript preparation. D.R.B. coordinated collection of peripheral venous blood samples, oversaw the management of HIV disease marker data, and assisted with manuscript preparation. S.D.W. and M.C. provided comments on the data analysis plan as well as assisted with interpretation of preliminary analyses and manuscript preparation. S.D. oversaw computer-based study assessment programming, managed study data, and assisted with manuscript preparation. E.D.R. assisted in the development of study hypotheses, oversaw collection of computer-based assessment data, provided comments on the data analysis plan, and assisted with the interpretation of preliminary analyses and manuscript preparation.
For making this study possible, the authors thank the study participants, Study Project Director, Jennifer Cohen, and study team, including Sujana Bhattacharyya, Shemena Campbell, Kara Marson and Deb Schneider. We also thank the teams of collaborating researchers including Richard Clark, John Day, Nelia Dela Cruz, Carina Flores, Minoo Gorji, David Guzman, Scot Hammond, Jackie Haslam, Zizi Hawthorne, Jay Jankowski, Rhonda Johnson, Mac McMaster, Sandra Monk, Rebecca Packard, Joyce Powell, Kathleen Ragland, Mathew Reynolds, Paul Rueckhaus, Jacqueline So, John Weeks and Kelly Winslow. This study was funded by NIH R01-DA15605, R01-MH54907, and UL1 RR024131.
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