Elise D. Riley

Adherence-resistance relationships for protease and non-nucleoside reverse transcriptase inhibitors explained by virological fitness.

Objective:To compare the prevalence of resistance by adherence level in patients treated with non-nucleoside reverse transcriptase inhibitors (NNRTI) or protease inhibitors (PI). Also to examine the mechanism of differential class-specific adherence–resistance relationships, focusing on the patient-derived capacity of wild-type and drug-resistant recombinant variants to replicate in vitro in the presence of variable drug levels. Methods:Participants received unannounced pill count measures to assess adherence, viral load monitoring, and genotypic resistance testing. The replicative capacity of drug-susceptible and drug-resistant recombinants was determined using a single-cycle recombinant phenotypic susceptibility assay. Drug exposure was estimated using population-averaged pharmacological measurements adjusted by participant-specific levels of adherence. Results:In the NNRTI-treated group, 69% had resistance at 0–48% adherence compared to 13% at 95–100% (P = 0.01). PI resistance was less common than NNRTI resistance at 0–48% adherence (69% versus 23%; P = 0.01). In multivariate analysis, the odds for PI resistance increased (P = 0.03) while the odds for NNRTI resistance decreased (P = 0.04) with improving adherence. Individuals with drug-resistant variants were more likely to have levels of drug exposure where the resistant variant was more fit than the drug-susceptible variant in vitro, while those with drug-susceptible virus were more likely to have levels of drug exposure where the drug-susceptible virus was more fit than the drug-resistant variant (P = 0.005). Conclusions:NNRTI resistance was more common than PI resistance at low levels of adherence. Class-specific adherence–resistance relationships are associated with the relative replicative capacity of drug-resistant versus wild-type variants to replicate in the presence of clinically relevant drug levels.

Acceptance and adherence with antiretroviral therapy among HIV-infected women in a correctional facility

We examined attitudinal and demographic correlates of antiretroviral acceptance and adherence among incarcerated HIV-infected women. Structured interviews were conducted with 102 HIV-infected female prisoners eligible for antiretroviral therapy. Three quarters of the women were currently taking antiretroviral agents, of whom 62% were adherent to therapy. Satisfaction was very high with the HIV care offered at the prison; 67% had been first offered antiretroviral agents while in prison. Univariate and multivariate analyses showed acceptance of the first offer of antiretroviral therapy to be associated with trust in medication safety, lower educational level, and non-black race. Current acceptance of therapy was associated with trust in the medications efficacy and safety. Medication adherence was correlated with the patient-physician relationship and presence of emotional supports. Nearly one half of these HIV-seropositive women were willing to take experimental HIV medications in prison. This was correlated with satisfaction with existing health care, the presence of HIV-related social supports, and perceived susceptibility to a worsening condition. Acceptance and adherence with antiretroviral agents appear to be significantly associated with trust in medications, trust in the health care system, and interpersonal relationships with physicians and peers. Development of models of care that encourage and support such relationships is essential for improving adherence to antiretroviral therapy, especially for populations that have historically been marginalized from mainstream medical care systems.

Food Insecurity is Associated with Incomplete HIV RNA Suppression Among Homeless and Marginally Housed HIV-infected Individuals in San Francisco

Background and ObjectivesThere is growing international concern that food insecurity may negatively impact antiretroviral (ARV) treatment outcomes, but no studies have directly evaluated the effect of food insecurity on viral load suppression and antiretroviral adherence. We hypothesized that food insecurity would be associated with poor virologic response among homeless and marginally housed HIV-positive ARV-treated patients.DesignThis is a cross-sectional study.Participants and SettingParticipants were ARV-treated homeless and marginally housed persons receiving adherence monitoring with unannounced pill counts in the Research on Access to Care in the Homeless (REACH) Cohort.MeasurementsFood insecurity was measured by the Household Food Insecurity Access Scale (HFIAS). The primary outcome was suppression of HIV viral RNA to <50 copies/ml. We used multivariate logistic regression to assess whether food insecurity was associated with viral suppression.ResultsAmong 104 participants, 51% were food secure, 24% were mildly or moderately food insecure and 25% were severely food insecure. Severely food insecure participants were less likely to have adherence >=80%. In adjusted analyses, severe food insecurity was associated with a 77% lower odds of viral suppression (95% CI = 0.06–0.82) when controlling for all covariates. In analyses stratified by adherence level, severe food insecurity was associated with an 85% lower odds of viral suppression (95% CI = 0.02–0.99) among those with <=80% adherence and a 66% lower odds among those with >80% adherence (95% CI = 0.06–1.81).ConclusionsFood insecurity is present in half of the HIV-positive urban poor in San Francisco, one of the best resourced settings for HIV-positive individuals in the United States, and is associated with incomplete viral suppression. These findings suggest that ensuring access to food should be an integral component of public health HIV programs serving impoverished populations.

Pillbox Organizers are Associated with Improved Adherence to HIV Antiretroviral Therapy and Viral Suppression: a Marginal Structural Model Analysis

BACKGROUND Pillbox organizers are inexpensive and easily used; however, their effect on adherence to antiretroviral medications is unknown. METHODS Data were obtained from an observational cohort of 245 human immunodeficiency virus (HIV)-infected subjects who were observed from 1996 through 2000 in San Francisco, California. Adherence was the primary outcome and was measured using unannounced monthly pill counts. Plasma HIV RNA level was considered as a secondary outcome. Marginal structural models were used to estimate the effect of pillbox organizer use on adherence and viral suppression, adjusting for confounding by CD4+ T cell count, viral load, prior adherence, recreational drug use, demographic characteristics, and current and past treatment. RESULTS Pillbox organizer use was estimated to improve adherence by 4.1%-4.5% and was associated with a decrease in viral load of 0.34-0.37 log10 copies/mL and a 14.2%-15.7% higher probability of achieving a viral load < or = 400 copies/mL (odds ratio, 1.8-1.9). All effect estimates were statistically significant. CONCLUSION Pillbox organizers appear to significantly improve adherence to antiretroviral therapy and to improve virologic suppression. We estimate that pillbox organizers may be associated with a cost of approximately

BRIEF REPORT: The Aging of the Homeless Population: Fourteen‐Year Trends in San Francisco

19,000 per quality-adjusted life-year. Pillbox organizers should be a standard intervention to improve adherence to antiretroviral therapy.

Psychiatric risk factors for HIV disease progression: the role of inconsistent patterns of antiretroviral therapy utilization.

AbstractBACKGROUND: Homelessness is associated with high rates of health and substance use problems. OBJECTIVE: To examine trends in the age, housing, health status, health service utilization, and drug use of the homeless population over a 14-year period. DESIGN: Serial cross-sectional. PARTICIPANTS: We studied 3,534 literally homeless adults recruited at service providers in San Francisco in 4 waves: 1990–1994, 1996–1998, 1999–2000, and 2003. MEASUREMENTS: Age, time homeless, self-reported chronic conditions, hospital and emergency department utilization, and drug and alcohol use. RESULTS: The median age of the homeless increased from 37 to 46 over the study waves, at a rate of 0.66 years per calendar year (P<.01). The median total time homeless increased from 12 to 39.5 months (P<.01). Emergency department visits, hospital admissions, and chronic health conditions increased. CONCLUSIONS: The homeless population is aging by about two thirds of a year every calendar year, consistent with trends in several other cities. It is likely that the homeless are static, aging population cohort. The aging trends suggest that chronic conditions will become increasingly prominent for homeless health services. This will present challenges to traditional approaches to screening, prevention, and treatment of chronic diseases in an aging homeless population.

BRIEF REPORT: Factors Associated with Depression Among Homeless and Marginally Housed HIV-Infected Men in San Francisco

Background:In the era of antiretroviral 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. Methods: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. Results:Elevated affective symptoms of depression independently predicted ART discontinuation [adjusted odds ratio = 1.39, 95% confidence interval (CI) = 1.08 to 1.78], and use of stimulants at least weekly independently predicted intermittent ART utilization (adjusted odds ratio = 2.62, 95% CI = 1.45 to 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 nonsignificant after accounting for inconsistent patterns of ART utilization, providing evidence of partial mediation. Conclusions:Inconsistent patterns of ART utilization may partially explain the effects of depression and stimulant use on hastened HIV disease progression.

Food insecurity and Hiv clinical outcomes in a longitudinal study of urban homeless and marginally housed Hiv-infected individuals

AbstractOBJECTIVES: To evaluate the prevalence of and factors associated with depression among HIV-infected homeless and marginally housed men. DESIGN: Cross-sectional study. PARTICIPANTS AND SETTING: Homeless and marginally housed men living with HIV in San Francisco identified from the Research on Access to Care in the Homeless (REACH) Cohort. MEASUREMENTS: The primary outcome was symptoms of depression, as measured by the Beck Depression Inventory (BDI). Multivariate logistic regression was used to identify associations of sociodemographic characteristics, drug and alcohol use, housing status, jail status, having a representative payee, health care utilization, and CD4 T lymphocyte counts. RESULTS: Among 239 men, 134 (56%) respondents screened positive for depression. Variables associated with depression in multivariate analysis included white race (adjusted odds ratio [AOR]=2.2. confidence interval [CI]=1.3 to 3.9), having a representative payee (AOR=2.4, CI=1.3 to 4.2), heavy alcohol consumption (AOR=4.7, CI=1.3 to 17.1), and recently missed medical appointments (AOR=2.6, CI=1.4 to 4.8). CONCLUSIONS: Depression is a major comorbidity among the HIV-infected urban poor. Given that missed medical appointments and alcohol use are likely indicators of depression and contributors to continued depression, alternate points of contact are necessary with many homeless individuals. Providers may consider partnering with payees to improve follow-up with individuals who are HIV-positive, homeless, and depressed.

Basic Subsistence Needs and Overall Health Among Human Immunodeficiency Virus-infected Homeless and Unstably Housed Women

Background:Food insecurity is common among HIV-infected individuals and has been associated with poor health. Little longitudinal research has examined the association of food insecurity with HIV clinical outcomes, or the extent to which adherence mediates these associations. Design:Observational cohort study Methods:HIV-infected homeless and marginally housed individuals in the San Francisco Research on Access to Care in the Homeless cohort completed quarterly structured interviews and blood draws. We measured food insecurity using the validated Household Food Insecurity Access Scale. Primary outcomes were: antiretroviral therapy (ART) nonadherence (<90% adherence), incomplete HIV viral load suppression more than 100 copies/ml, and CD4+ cell counts less than 200 cells/&mgr;l. We estimated model parameters using generalized estimating equations, adjusting for sociodemographic and clinical variables. Results:From May 2007 to March 2010, we followed 284 participants for a median of 22 months. At baseline 54.6% of participants were food-insecure. Food insecurity was associated with increased odds of ART nonadherence [adjusted odds ratio (AOR) = 1.48; 95% confidence interval (CI), 1.19–1.85], incomplete viral load suppression (AOR = 1.29, 95% CI 1.04–1.61), and CD4+ cell counts less than 200 cells/&mgr;l (AOR = 1.26, 95% CI 1.01–1.56). When we included ART adherence in adjusted models for incomplete viral suppression and CD4+ cell counts less than 200 cells/&mgr;l, the magnitude of the effect decreased slightly. Conclusion:Food insecurity was associated with poor HIV outcomes, including nonadherence, in a longitudinal study of US-based HIV-infected unstably housed individuals. Efforts to address food insecurity should be included in HIV-treatment programs, and may help improve health outcomes.

DRUG USER TREATMENT REFERRALS AND ENTRY AMONG PARTICIPANTS OF A NEEDLE EXCHANGE PROGRAM

Some gender differences in the progression of human immunodeficiency virus (HIV) infection have been attributed to delayed treatment among women and the social context of poverty. Recent economic difficulties have led to multiple service cuts, highlighting the need to identify factors with the most influence on health in order to prioritize scarce resources. The aim of this study was to empirically rank factors that longitudinally impact the health status of HIV-infected homeless and unstably housed women. Study participants were recruited between 2002 and 2008 from community-based venues in San Francisco, California, and followed over time; marginal structural models and targeted variable importance were used to rank factors by their influence. In adjusted analysis, the factor with the strongest effect on overall mental health was unmet subsistence needs (i.e., food, hygiene, and shelter needs), followed by poor adherence to antiretroviral therapy, not having a close friend, and the use of crack cocaine. Factors with the strongest effects on physical health and gynecologic symptoms followed similar patterns. Within this population, an inability to meet basic subsistence needs has at least as much of an effect on overall health as adherence to antiretroviral therapy, suggesting that advances in HIV medicine will not fully benefit indigent women until their subsistence needs are met.