Allan Rodriguez

Early Virologic Nonresponse to Tenofovir, Abacavir, and Lamivudine in HIV-Infected Antiretroviral-Naive Subjects

BACKGROUND Antiretroviral combinations that reduce the number of pills and dosing frequency have the potential to simplify therapy. We compared 2 regimens dosed as 2 pills once daily. METHODS This was a randomized, open-label, multicenter study of tenofovir disoproxil fumarate versus efavirenz, both administered once daily with the abacavir/lamivudine fixed-dose combination in treatment-naive human immunodeficiency virus type 1 (HIV-1)-infected subjects. After reports of early nonresponse, an unplanned interim analysis was performed. Virologic nonresponse was defined as (1) a <2.0-log(10) copies/mL decrease in HIV-1 RNA level by week 8, (2) an HIV-1 RNA rebound of > or =1.0 log(10) copies/mL above the nadir, or (3) for subjects with 2 consecutive HIV-1 RNA measurements <50 copies/mL, a subsequent increase to >400 copies/mL on 2 consecutive occasions. RESULTS We randomized 340 subjects. Median baseline HIV-1 RNA level and CD4+ cell count were 4.7 log(10) copies/mL and 251 cells/mm3, respectively; 194 subjects with HIV-1 RNA data from > or =8 weeks were included in the interim analysis. Virologic nonresponse occurred in 50 (49%) of 102 subjects in the tenofovir disoproxil fumarate arm, compared with 5 (5%) of 92 of subjects in the efavirenz arm (P<.001). Within 12 weeks, viral genotypes for nonresponders in the tenofovir disoproxil fumarate arm showed M184V or I/M/V mixtures in 40 (98%) of 41 subjects and K65R and M184V or mixtures in 22 (54%) of 41 subjects. The protocol was immediately amended to modify the tenofovir disoproxil fumarate arm. The efavirenz arm continued unchanged; after 48 weeks, 120 (71%) of 169 subjects achieved HIV-1 RNA levels <50 copies/mL. CONCLUSION The tenofovir disoproxil fumarate/abacavir/lamivudine regimen resulted in an unexpected and unacceptably high rate of nonresponse and incidence of K65R and M184V/I. This 3-drug regimen should not be used.

Measuring Retention in HIV Care: The Elusive Gold Standard

Background:Measuring retention in HIV primary care is complex, as care includes multiple visits scheduled at varying intervals over time. We evaluated 6 commonly used retention measures in predicting viral load (VL) suppression and the correlation among measures. Methods:Clinic-wide patient-level data from 6 academic HIV clinics were used for 12 months preceding implementation of the Centers for Disease Control and Prevention/Health Resources and Services Administration (CDC/HRSA) retention in care intervention. Six retention measures were calculated for each patient based on scheduled primary HIV provider visits: count and dichotomous missed visits, visit adherence, 6-month gap, 4-month visit constancy, and the HRSA HIV/AIDS Bureau (HRSA HAB) retention measure. Spearman correlation coefficients and separate unadjusted logistic regression models compared retention measures with one another and with 12-month VL suppression, respectively. The discriminatory capacity of each measure was assessed with the c-statistic. Results:Among 10,053 patients, 8235 (82%) had 12-month VL measures, with 6304 (77%) achieving suppression (VL <400 copies/mL). All 6 retention measures were significantly associated (P < 0.0001) with VL suppression (odds ratio; 95% CI, c-statistic): missed visit count (0.73; 0.71 to 0.75, 0.67), missed visit dichotomous (3.2; 2.8 to 3.6, 0.62), visit adherence (3.9; 3.5 to 4.3,0.69), gap (3.0; 2.6 to 3.3, 0.61), visit constancy (2.8; 2.5 to 3.0, 0.63), and HRSA HAB (3.8; 3.3 to 4.4, 0.59). Measures incorporating “no-show” visits were highly correlated (Spearman coefficient = 0.83–0.85), as were measures based solely on kept visits (Spearman coefficient = 0.72–0.77). Correlation coefficients were lower across these 2 groups of measures (range = 0.16–0.57). Conclusions:Six retention measures displayed a wide range of correlation with one another, yet each measure had significant association and modest discrimination for VL suppression. These data suggest there is no clear gold standard and that selection of a retention measure may be tailored to context.

HIV treatment in drug abusers: impact of alcohol use

Studies of alcohol use in HIV‐1 infected patients have resulted in conflicting and limited information regarding prevalence, as well as impact on HIV replication, disease progression and response to antiretroviral therapy. Alcohol, drug abuse and past medical information, including antiretroviral treatment, were obtained using research questionnaires and medical chart review in 220 HIV‐1 infected drug users. A physical examination was conducted and blood was drawn to evaluate immune measures and nutritional status. Heavy alcohol consumption, defined as daily or 3‐4 times per/week, was reported in 63% of the cohort. Men (odds ratio (OR)=2.6, 95% CI 1.13‐5.99, p =0.013), and participants between 35 and 45 years of age were three times more likely to be heavy alcohol users (p =0.006 and 0.0009, respectively). Low serum albumin levels were more evident in heavy alcohol users than non‐drinkers (p =0.003). Heavy alcohol users receiving antiretroviral therapy were twice as likely to have CD4 counts below 500 than light or non‐drinkers (95% CI, 1‐5.5, p =0.03), and highly active antiretroviral therapy (HAART)‐treated heavy alcohol users were four times less likely to achieve a positive virological response (95% CI, 1.2‐17, p =0.04). Alcohol consumption is prevalent in our HIV‐1 infected drug user cohort and significantly impacts both immunological and virological response to HAART treatment.

Prevalence of Antiretroviral Drug Resistance and Resistance-Associated Mutations in Antiretroviral Therapy-Naïve HIV-Infected Individuals from 40 United States Cities

Abstract Background: Transmission of drug-resistant HIV strains to antiretroviral therapy (ART)-naïve subjects can negatively impact therapy response. As treatment strategies and utilization of antiretroviral drugs evolve, patterns of transmitted mutations may shift. Method: Paired genotypic and phenotypic susceptibility data were retrospectively analyzed for 317 ART-naïve, HIV–infected subjects from 40 small and major metropolitan cities in the Northeastern, Midwestern, Southern, Southwestern, and Northwestern United States during 2003. Results: Using current (January 2007) PhenoSense cutoffs, HIV-from 8% of subjects had reduced susceptibility to ⩾1 drug. By class, >% had reduced susceptibility to protease inhibitors (PIs), and % had reduced susceptibility to nucleoside reverse transcriptase inhibitors (NRTIs); reduced susceptibility to ⩾1 non–nucleoside reverse transcriptase inhibitor (NNRTIs) was seen in 7% of subjects, with 4% of all subjects having reduced susceptibility to all NNRTIs. IAS–USA–defined NRTI, NNRTI, and/or major PI HIV–drug resistance–associated mutations were detected for 0% of the subjects. HIV risk factors included homosexual contact (74%), heterosexual contact (28%), and injectable drug use/transfusion/other (7%.Reduced susceptibility to ⩾1 drug was significantly higher (p = .034) for white subjects than African Americansand Hispanics/others. Conclusion: The high prevalence of drug resistance in these ART–naïve subjects suggests thattransmitted resistance is occurring widely within the United States. HIV genotyping and/or phenotyping for antiretroviral-naïve patients seeking treatment should be considered, especially if the therapy will include an NNRTI.

Impact of a Selenium Chemoprevention Clinical Trial on Hospital Admissions of HIV-Infected Participants

Abstract Purpose: To evaluate the impact of selenium chemoprevention (200μg/day) on hospitalizations in HIV-positive individuals. Method: Data were obtained from 186 HIV+ men and women participating in a randomized, double-blind, placebo-controlled selenium clinical trial (1998-2000). Supplements were dispensed monthly, and clinical evaluations were conducted every 6 months. Inpatient hospitalizations, hospitalization costs, and rates of hospitalization were determined 2 years before and during the trial. Results: At enrollment, no significant differences in CD4 cell counts or viral burden were observed between the two study arms. Fewer placebo-treated participants were using antiretrovirals (p < .05). The total number of hospitalizations declined from 157 before the trial to 103 during the 2 year study. A marked decrease in total admission rates (RR = 0.38; p = .002) and percent of hospitalizations due to infection/100 patients for those receiving selenium was observed (p = .01). As a result, the cost for hospitalization decreased 58% in the selenium group, compared to a 30% decrease in the placebo group (p = .001). In the final analyses, selenium therapy continued to be a significant independent factor associated with lower risk of hospitalization (p = .001). Conclusion: Selenium supplementation appears to be a beneficial adjuvant treatment to decrease hospitalizations as well as the cost of caring for HIV-1--infected patients.PURPOSE To evaluate the impact of selenium chemoprevention (200 microg/day) on hospitalizations in HIV-positive individuals. METHOD Data were obtained from 186 HIV+ men and women participating in a randomized, double-blind, placebo-controlled selenium clinical trial (1998-2000). Supplements were dispensed monthly, and clinical evaluations were conducted every 6 months. Inpatient hospitalizations, hospitalization costs, and rates of hospitalization were determined 2 years before and during the trial. RESULTS At enrollment, no significant differences in CD4 cell counts or viral burden were observed between the two study arms. Fewer placebo-treated participants were using antiretrovirals (p <.05). The total number of hospitalizations declined from 157 before the trial to 103 during the 2 year study. A marked decrease in total admission rates (RR = 0.38; p =.002) and percent of hospitalizations due to infection/100 patients for those receiving selenium was observed (p =.01). As a result, the cost for hospitalization decreased 58% in the selenium group, compared to a 30% decrease in the placebo group (p =.001). In the final analyses, selenium therapy continued to be a significant independent factor associated with lower risk of hospitalization (p =.001). CONCLUSION Selenium supplementation appears to be a beneficial adjuvant treatment to decrease hospitalizations as well as the cost of caring for HIV-1-infected patients.

Enhanced Personal Contact With HIV Patients Improves Retention in Primary Care: A Randomized Trial in 6 US HIV Clinics

BACKGROUND The aim of the study was to determine whether enhanced personal contact with human immunodeficiency virus (HIV)-infected patients across time improves retention in care compared with existing standard of care (SOC) practices, and whether brief skills training improves retention beyond enhanced contact. METHODS The study, conducted at 6 HIV clinics in the United States, included 1838 patients with a recent history of inconsistent clinic attendance, and new patients. Each clinic randomized participants to 1 of 3 arms and continued to provide SOC practices to all enrollees: enhanced contact with interventionist (EC) (brief face-to-face meeting upon returning for care visit, interim visit call, appointment reminder calls, missed visit call); EC + skills (organization, problem solving, and communication skills); or SOC only. The intervention was delivered by project staff for 12 months following randomization. The outcomes during that 12-month period were (1) percentage of participants attending at least 1 primary care visit in 3 consecutive 4-month intervals (visit constancy), and (2) proportion of kept/scheduled primary care visits (visit adherence). RESULTS Log-binomial risk ratios comparing intervention arms against the SOC arm demonstrated better outcomes in both the EC and EC + skills arms (visit constancy: risk ratio [RR], 1.22 [95% confidence interval {CI}, 1.09-1.36] and 1.22 [95% CI, 1.09-1.36], respectively; visit adherence: RR, 1.08 [95% CI, 1.05-1.11] and 1.06 [95% CI, 1.02-1.09], respectively; all Ps < .01). Intervention effects were observed in numerous patient subgroups, although they were lower in patients reporting unmet needs or illicit drug use. CONCLUSIONS Enhanced contact with patients improved retention in HIV primary care compared with existing SOC practices. A brief patient skill-building component did not improve retention further. Additional intervention elements may be needed for patients reporting illicit drug use or who have unmet needs. CLINICAL TRIALS REGISTRATION CDCHRSA9272007.

Impact of selenium status on the pathogenesis of mycobacterial disease in HIV-1-infected drug users during the era of highly active antiretroviral therapy

&NA; The risk of mycobacterial disease is significantly increased in drug abusers as well as in immunocompromised HIV‐1‐infected individuals. The essential trace element selenium has an important function in maintaining immune processes and may, thus, have a critical role in clearance of mycobacteria. The impact of selenium status on the development of mycobacterial diseases in HIV‐1‐seropositive drug users was investigated over a 2‐year period (1999‐2001). Twelve cases of mycobacterial disease (tuberculosis, 9; infection due to atypical Mycobacterium species, 3) occurred; these 12 cases were compared with 32 controls with no history of respiratory infections who were matched on age, sex, and HIV status. Significant risk for development of mycobacterial disease was associated with a CD4 cell count of <200/mm3, malnutrition, and selenium levels of ⩽135 μg/L (patients with these levels were 13 times more likely to develop mycobacterial disease). Multivariate analyses controlling for antiretroviral treatment and CD4 cell count revealed that both body mass index and selenium level remained significant factors in the relative risk for developing mycobacterial disease (relative risk, 3; p = .015); these findings suggest that selenium status may have a profound impact on the pathogenesis of mycobacterial disease.

Numeracy Skills Explain Racial Differences in HIV Medication Management

Racial disparities in HIV/AIDS are well established and efforts to understand key factors that may explain these differences are needed. Recent evidence suggests that health literacy may contribute to disparities in health behaviors among African American HIV patients. One component of health literacy, numeracy, is emerging as an important skill for successful self management of medications. We therefore tested whether numeracy mediated the effects of race on medication management among HIV seropositive patients. Results showed that poor management of a simulated HIV medication regimen among African Americans and women was mediated by lower numeracy. Poor medication self-management may be a significant root cause for health disparities in African Americans with HIV/AIDS. Whether African American women may be at particular risk requires further study. Interventions to improve HIV medication self-management through addressing numeracy skills may help to narrow the gap in health disparities among African Americans with HIV/AIDS.

Depressive symptoms and food insufficiency among HIV-infected crack users in atlanta and miami

Depression contributes to worse general and HIV-related clinical outcomes. We examined the prevalence of and factors associated with depressive symptomatology among HIV-infected crack cocaine users recruited for Project HOPE (Hospital Visit is an Opportunity for Prevention and Engagement with HIV-positive Crack Users). We used multiple logistic regression to determine sociodemographic correlates associated with screening in for depression. Among 291 participants, three-quarters (73.5%) were identified as depressed. Higher odds of screening in for depression was associated with food insufficiency and monthly income below

Food insufficiency among HIV-infected crack-cocaine users in Atlanta and Miami.

600. Alcohol and crack use were not associated with screening in for depression. Depressive symptomatology is extremely prevalent among HIV-infected crack cocaine users and is associated with food insufficiency and lower income. Screening for depression and food insecurity should be included in HIV prevention and treatment programs. Improved recognition and mitigation of these conditions will help alleviate their contribution to HIV-related adverse health outcomes.