Antiretroviral regimen and suboptimal medication adherence are associated with low-level human immunodeficiency virus viremia.

Episodes of human immunodeficiency virus low-level viremia (LLV) are common in the clinical setting, but its association with antiretroviral therapy (ART) regimen and adherence remains unclear. Antiretroviral therapy adherence was evaluated in participants of the Research on Access to Care in the Homeless cohort by unannounced pill counts. Factors associated with increased risk of LLV include treatment with a protease inhibitor (PI)-based regimen (ritonavir-boosted PI vs nonnucleoside reverse-transcriptase inhibitor: adjusted hazard ratio [HR], 3.1; P = .01) and lower ART adherence over the past 3 months (HR, 1.1 per 5% decreased adherence, adjusted; P = .050). Patients with LLV may benefit from ART adherence counseling and potentially regimen modification.

Longitudinal assessment of associations between food insecurity, antiretroviral adherence and HIV treatment outcomes in rural Uganda.

INTRODUCTION: Food insecurity is a potentially important barrier to the success of antiretroviral therapy (ART) programs in resource-limited settings. We undertook a longitudinal study in rural Uganda to estimate the associations between food insecurity and HIV treatment outcomes. DESIGN: Longitudinal cohort study. METHODS: Participants were from the Uganda AIDS Rural Treatment Outcomes study and were followed quarterly for blood draws and structured interviews. We measured food insecurity with the validated Household Food Insecurity Access Scale. Our primary outcomes were: ART nonadherence (adherence <90%) measured by visual analog scale; incomplete viral load suppression (>400 copies/ml); and low CD4 T-cell count (<350 cells/µl). We used generalized estimating equations to estimate the associations, adjusting for socio-demographic and clinical variables. RESULTS: We followed 438 participants for a median of 33 months; 78.5% were food insecure at baseline. In adjusted analyses, food insecurity was associated with higher odds of ART nonadherence [adjusted odds ratio (AOR) 1.56, 95% confidence interval (CI) 1.10-2.20, P < 0.05], incomplete viral suppression (AOR 1.52, 95% CI 1.18-1.96, P < 0.01), and CD4 T-cell count less than 350 (AOR 1.47, 95% CI 1.24-1.74, P < 0.01). Adding adherence as a covariate to the latter two models removed the association between food insecurity and viral suppression, but not between food insecurity and CD4 T-cell count. CONCLUSIONS: Food insecurity is longitudinally associated with poor HIV outcomes in rural Uganda. Intervention research is needed to determine the extent to which improved food security is causally related to improved HIV outcomes and to identify the most effective policies and programs to improve food security and health.

Multiple measures reveal antiretroviral adherence successes and challenges in HIV-infected Ugandan children.

BACKGROUND: Adherence to HIV antiretroviral therapy (ART) among children in developing settings is poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: To understand the level, distribution, and correlates of ART adherence behavior, we prospectively determined monthly ART adherence through multiple measures and six-monthly HIV RNA levels among 121 Ugandan children aged 2-10 years for one year. Median adherence levels were 100% by three-day recall, 97.4% by 30-day visual analog scale, 97.3% by unannounced pill count/liquid formulation weights, and 96.3% by medication event monitors (MEMS). Interruptions in MEMS adherence of ≥ 48 hours were seen in 57.0% of children; 36.3% had detectable HIV RNA at one year. Only MEMS correlated significantly with HIV RNA levels (r = -0.25, p = 0.04). Multivariable regression found the following to be associated with <90% MEMS adherence: hospitalization of child (adjusted odds ratio [AOR] 3.0, 95% confidence interval [CI] 1.6-5.5; p = 0.001), liquid formulation use (AOR 1.4, 95%CI 1.0-2.0; p = 0.04), and caregiver's alcohol use (AOR 3.1, 95%CI 1.8-5.2; p<0.0001). Child's use of co-trimoxazole (AOR 0.5, 95%CI 0.4-0.9; p = 0.009), caregiver's use of ART (AOR 0.6, 95%CI 0.4-0.9; p = 0.03), possible caregiver depression (AOR 0.6, 95%CI 0.4-0.8; p = 0.001), and caregiver feeling ashamed of child's HIV status (AOR 0.5, 95%CI 0.3-0.6; p<0.0001) were protective against <90% MEMS adherence. Change in drug manufacturer (AOR 4.1, 95%CI 1.5-11.5; p = 0.009) and caregiver's alcohol use (AOR 5.5, 95%CI 2.8-10.7; p<0.0001) were associated with ≥ 48-hour interruptions by MEMS, while second-line ART (AOR 0.3, 95%CI 0.1-0.99; p = 0.049) and increasing assets (AOR 0.7, 95%CI 0.6-0.9; p = 0.0007) were protective against these interruptions. CONCLUSIONS/SIGNIFICANCE: Adherence success depends on a well-established medication taking routine, including caregiver support and adequate education on medication changes. Caregiver-reported depression and shame may reflect fear of poor outcomes, functioning as motivation for the child to adhere. Further research is needed to better understand and build on these key influential factors for adherence intervention development.

Real-time electronic adherence monitoring is feasible, comparable to unannounced pill counts, and acceptable.

Second generation electronic medication adherence monitors provide real-time data on pill bottle opening behavior. Feasibility, validity, and acceptability, however, have not been established. Med-eMonitor is a multi-compartment adherence device with reminder and education capacity that transmits data through a telephone connection. Monthly adherence levels were measured for 52 participants over approximately 3 months using the Med-eMonitor (unadjusted and adjusted for participant confirmed dosing) and unannounced pill counts. HIV RNA was assessed before and after the 3-month period. Acceptability of Med-eMonitor was determined. Over 92% of Med-eMonitor data was transmitted daily. Unannounced pill counts significantly correlated with adjusted Med-eMonitor adherence (r = 0.29, P = 0.04). HIV RNA significantly correlated with unannounced pill counts (r = -0.34, P = 0.02), and trended toward a significant correlation with unadjusted Med-eMonitor adherence (r = -0.26; P = 0.07). Most, but not all, participants liked using the Med-eMonitor. Med-eMonitor allows for real-time adherence monitoring and potentially intervention, which may be critical for prolonging treatment success.

A marginal structural model to estimate the causal effect of antidepressant medication treatment on viral suppression among homeless and marginally housed persons with HIV.

CONTEXT: Depression strongly predicts nonadherence to human immunodeficiency virus (HIV) antiretroviral therapy, and adherence is essential to maintaining viral suppression. This suggests that pharmacologic treatment of depression may improve virologic outcomes. However, previous longitudinal observational analyses have inadequately adjusted for time-varying confounding by depression severity, which could yield biased estimates of treatment effect. Application of marginal structural modeling to longitudinal observation data can, under certain assumptions, approximate the findings of a randomized controlled trial. OBJECTIVE: To determine whether antidepressant medication treatment increases the probability of HIV viral suppression. DESIGN: Community-based prospective cohort study with assessments conducted every 3 months. SETTING: Community-based research field site in San Francisco, California. PARTICIPANTS: One hundred fifty-eight homeless and marginally housed persons with HIV who met baseline immunologic (CD4+ T-lymphocyte count, <350/µL) and psychiatric (Beck Depression Inventory II score, >13) inclusion criteria, observed from April 2002 through August 2007. MAIN OUTCOME MEASURES: Probability of achieving viral suppression to less than 50 copies/mL. Secondary outcomes of interest were probability of being on an antiretroviral therapy regimen, 7-day self-reported percentage adherence to antiretroviral therapy, and probability of reporting complete (100%) adherence. RESULTS: Marginal structural models estimated a 2.03 greater odds of achieving viral suppression (95% confidence interval [CI], 1.15-3.58; P = .02) resulting from antidepressant medication treatment. In addition, antidepressant medication use increased the probability of antiretroviral uptake (weighted odds ratio, 3.87; 95% CI, 1.98-7.58; P < .001). Self-reported adherence to antiretroviral therapy increased by 25 percentage points (95% CI, 14-36; P < .001), and the odds of reporting complete adherence nearly doubled (weighted odds ratio, 1.94; 95% CI, 1.20-3.13; P = .006). CONCLUSIONS: Antidepressant medication treatment increases viral suppression among persons with HIV. This effect is likely attributable to improved adherence to a continuum of HIV care, including increased uptake and adherence to antiretroviral therapy.

A single tablet regimen is associated with higher adherence and viral suppression than multiple tablet regimens in HIV+ homeless and marginally housed people.

BACKGROUND: Although, single-tablet regimen (STR) efavirenz, emtricibine, and tenofovir disoproxil fumarate (EFV/FTC/TDF) may be appealing in HIV-infected persons who are at high risk for nonadherence, the degree to which this simplified formulation affects adherence is not known. The virologic effectiveness of this STR in a potentially nonadherent population remains a concern, given the rapid selection of drug resistance seen with these drugs. METHOD: We performed a prospective observational study assessing adherence and virologic response to EFV/FTC/TDF STR among a cohort of homeless and marginally housed individuals. We compared adherence and viral suppression to historical controls followed in the same cohort. RESULTS: Adherence was higher in EFV/FTC/TDF STR regimen compared to non-one-pill-once-daily therapy (P = 0.006) after controlling for multiple confounders. Viral suppression (HIV RNA <50 copies/ml) was greater in EFV/ FTC/TDF STR than non-one-pill-once-daily regimens (69.2 versus 46.5%; P = 0.02), but there was no difference in viral suppression after controlling for adherence. CONCLUSION: Once-daily EFV/TNF/FTC STR appears to be a reasonable option for individuals with multiple barriers to adherence. Randomized clinical trials addressing various therapeutic strategies for this patient population are needed.

Average adherence to boosted protease inhibitor therapy, rather than the pattern of missed doses, as a predictor of HIV RNA replication.

Consecutive missed doses may differentially impact the efficacy of antiretroviral therapy associated with the use of a nonnucleoside reverse-transcriptase inhibitor (NNRTI) and a ritonavir-boosted protease inhibitor (PI). In a cohort of 72 subjects receiving a boosted PI, average adherence to dosage was a better predictor of human immunodeficiency virus (HIV) replication than was the duration or frequency of treatment interruption. In contrast with an NNRTI, consecutive missed doses of a boosted PI did not emerge as a major risk factor for HIV replication.

Food insecurity among homeless and marginally housed individuals living with HIV/AIDS in San Francisco.

Food insecurity is a risk factor for both HIV transmission and worse HIV clinical outcomes. We examined the prevalence of and factors associated with food insecurity among homeless and marginally housed HIV-infected individuals in San Francisco recruited from the Research on Access to Care in the Homeless Cohort. We used multiple logistic regression to determine socio-demographic and behavioral factors associated with food insecurity, which was measured using the Household Food Insecurity Access Scale. Among 250 participants, over half (53.6%) were food insecure. Higher odds of food insecurity was associated with being white, low CD4 counts, recent crack use, lack of health insurance, and worse physical and mental health. Food insecurity is highly prevalent among HIV-infected marginally housed individuals in San Francisco, and is associated with poor physical and mental health and poor social functioning. Screening for and addressing food insecurity should be a critical component of HIV prevention and treatment programs.

Longitudinal antiretroviral adherence in HIV+ Ugandan parents and their children initiating HAART in the MTCT-Plus family treatment model: role of depression in declining adherence over time.

We conducted a study to assess the effect of family-based treatment on adherence amongst HIV-infected parents and their HIV-infected children attending the Mother-To-Child-Transmission Plus program in Kampala, Uganda. Adherence was assessed using home-based pill counts and self-report. Mean adherence was over 94%. Depression was associated with incomplete adherence on multivariable analysis. Adherence declined over time. Qualitative interviews revealed lack of transportation money, stigma, clinical response to therapy, drug packaging, and cost of therapy may impact adherence. Our results indicate that providing ART to all eligible HIV-infected members in a household is associated with excellent adherence in both parents and children. Adherence to ART among new parents declines over time, even when patients receive treatment at no cost. Depression should be addressed as a potential barrier to adherence. Further study is necessary to assess the long-term impact of this family treatment model on adherence to ART in resource-limited settings.

Food insecurity is associated with incomplete HIV RNA suppression among homeless and marginally housed HIV-infected individuals in San Francisco.

BACKGROUND AND OBJECTIVES: There 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. DESIGN: This is a cross-sectional study. PARTICIPANTS AND SETTING: Participants 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. MEASUREMENTS: Food 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. RESULTS: Among 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 > or =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 < or =80% adherence and a 66% lower odds among those with >80% adherence (95% CI = 0.06-1.81). CONCLUSIONS: Food 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.

Implementation of the Medicare Part D prescription drug benefit is associated with antiretroviral therapy interruptions.

Antiretroviral (ARV) treatment interruptions are associated with virologic rebound, drug resistance, and increased morbidity and mortality. The Medicare Part D prescription drug benefit, implemented on January 1st, 2006, increased consumer cost-sharing. Consumer cost-sharing is associated with decreased access to medications and adverse clinical outcomes. We assessed the association of Part D implementation with treatment interruptions by studying 125 HIV-infected homeless and marginally housed individuals with drug coverage receiving ARV therapy. Thirty-five percent of respondents reported Medicare coverage and 11% reported ARV interruptions. The odds of ARV interruptions were six times higher among those with Part D coverage and remained significant after adjustment. The majority of Part D-covered respondents reporting ARV interruptions cited increased cost as their primary barrier. Directed interventions to monitor the long-term effects of increased cost burden on interruptions and clinical outcomes and to reduce cost burden are necessary to avoid preventable increases in morbidity and mortality.

Treatment interruptions predict resistance in HIV-positive individuals purchasing fixed-dose combination antiretroviral therapy in Kampala, Uganda.

OBJECTIVE: To evaluate adherence, treatment interruptions, and outcomes in patients purchasing antiretroviral fixed-dose combination (FDC) therapy. DESIGN: Ninety-seven participants were recruited into a prospective 24-week observational cohort study of HIV-positive, antiretroviral-naive individuals initiating self-pay Triomune or Maxivir therapy in Kampala, Uganda. Adherence was measured by monthly structured interview, unannounced home pill count, and electronic medication monitors (EMM). Treatment interruptions were measured as continuous intervals greater than 48 h without opening the EMM. The primary outcomes were survival with viral suppression below 400 copies/ml, CD4 cell increases, and genotypic drug resistance at 24 weeks. RESULTS: The median baseline CD4 cell count was 56 cells/microl and median log10 copies RNA/ml was 5.54; mean adherence ranged from 82 to 95% for all measures but declined significantly over time. In an intent-to-treat analysis, 70 (72%) patients had an undetectable plasma HIV-RNA level at week 24. Sixty-two of 95 (65%) individuals with continuous EMM data had a treatment interruption of greater than 48 h. Treatment interruptions accounted for 90% of missed doses. None of 33 participants who did not interrupt treatment for over 48 h had drug resistance, whereas eight of 62 (13%) participants who did interrupt therapy experienced drug resistance. Antiretroviral resistance was seen in 8% of individuals and overall mortality was 10% at 24 weeks. CONCLUSION: HIV-positive individuals purchasing generic FDC antiretroviral therapy have high rates of adherence and viral suppression, low rates of antiretroviral resistance, and robust CD4 cell responses. Adherence is an important predictor of survival with full viral suppression. Treatment interruptions are an important predictor of drug resistance.

The impact of chronic hepatitis C on health-related quality of life in homeless and marginally housed individuals with HIV.

Although infection with Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) frequently co-exist, there has been little research to determine the effects of HIV/HCV co-infection on health-related quality of life (HRQOL). We performed a cross-sectional analysis of baseline data from 216 participants enrolled in a community based study of HIV-infected homeless and marginally housed individuals, using multivariable linear regression analysis to determine if co-infection with HCV was independently associated with lower short-form 36 (SF-36) questionnaire scores. We found that individuals with HCV had significantly lower mean SF-36 scores in the domains of physical functioning, bodily pain, social functioning and role limitation due to emotional health, and that HIV/HCV co-infection was independently associated with a lower physical component score but not a lower mental component score after controlling for numerous covariates. These results suggest that co-infection with HCV may have an adverse effect on HRQOL among homeless and marginally housed individuals with HIV.

Brief report: Factors associated with depression among homeless and marginally housed HIV-infected men in San Francisco.

OBJECTIVES: 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.

Provider assessment of eligibility for hepatitis C treatment in HIV-infected homeless and marginally housed persons.

PURPOSE: To characterize the group of providers delivering medical care to HIV and hepatitis C (HCV) co-infected homeless and marginally housed individuals in San Francisco and to assess factors affecting provider decisions to initiate HCV treatment in this population. SUBJECTS AND METHODS: The Research in Access to Care for the Homeless (REACH) cohort is a representative sample of HIV-infected homeless and marginally housed individuals identified from single room occupancy hotels, homeless shelters and free lunch programs in San Francisco. Primary care providers (PCP) for active, HIV/HCV co-infected REACH cohort participants were administered face-to-face, semi-structured interviews. REACH participants were administered quarterly face-to-face structured interviews. RESULTS: 52/62 (83.9%) providers were interviewed regarding 133/155 (85.8%) active, HIV/HCV co-infected patients. Providers classified 94/133 (70.7%) patients as ineligible for HCV treatment. The mean number of reasons for ineligibility was 3.2. Most frequent reasons for provider determination of ineligibility included likelihood of poor medication adherence, depression, active injection drug use and patient disinterest in treatment. In addition, structural barriers to treatment included poor access to testing, delays in evaluation by a gastroenterologist and exclusion from treatment of patients with comorbidities. CONCLUSIONS: While HCV infection is common, HCV treatment is rare in the HIV/HCV coinfected urban poor. On average, the PCP in this study are experienced and are familiar with this patient population. There are many reasons for providers classifying patients as ineligible for HCV treatment. While these reasons indicate that treatment is difficult given chaotic lifestyle and concurrent medical conditions of this population, they are not insurmountable barriers. New treatments and strategies are necessary to treat this population with high rates of hepatitis C infection.

Spatial analysis of childhood leukemia in a case/control study.

A simple and direct analysis of the spatial distribution of childhood leukemia was performed using geographic data from a large case/control study. The data consist of cases of childhood leukemia and their corresponding birth cohort controls located in seven San Francisco Bay Area counties. Both parametric and randomization analyses show no evidence of a non-random spatial pattern of childhood leukemia among six of these counties. The data from San Francisco County, however, produce a moderately small significance probability (0.08) arising from a distance analysis and a significant p-value (0.01) arising from a frequency analysis of concordant case pairs. Although these p-values accurately reflect the probability of the observed spatial pattern occurring by chance alone, these results are based on only four cases of leukemia.

Initial treatment for prostate carcinoma in relation to comorbidity and symptoms.

BACKGROUND: Evidence suggests the type of treatment received for prostate carcinoma is associated with comorbidity, but little information is available on associations with specific comorbid disease or symptoms. The authors examined the relations between treatment and comorbidity, specific comorbid disease, and symptoms. METHODS: Medical records were abstracted for 1054 male members of the Kaiser Permanente medical care program diagnosed with prostate carcinoma from 1975 to 1987. Information was obtained on demographic characteristics, comorbid conditions, symptoms, tumor stage and grade, and treatment. Logistic regression was used to determine the significant predictors of treatment (radiation vs. nonaggressive treatment and surgery vs. nonaggressive treatment). RESULTS: Compared to nonaggressive treatment, radiation treatment was less likely among men who had prior cancer (adjusted odds ratio [OR] 0.29, 95% confidence interval [CI] 0.09-0.90) or cerebrovascular disease (OR 0.33, 95% CI 0.13-0.83). There was a significant interaction between race and myocardial infarction (P = 0.02). Surgery, compared to nonaggressive treatment, was less common among men with a prior cancer (OR 0.21, 95% CI 0.07-0.63) or congestive heart failure (OR 0.29, 95% CI 0.09-0.90). Significant interactions were observed between race and myocardial infarction (P = 0.01), diabetes and dysuria or hematuria (P = 0.02), and para- or hemiplegia and urinary frequency or nocturia (P = 0.01). CONCLUSIONS: Specific symptoms and comorbidity appear to influence treatment for prostate carcinoma. More research is needed on treatment differences by race.