Duncan Smith-Rohrberg Maru

Superiority of Directly Administered Antiretroviral Therapy over Self-Administered Therapy among HIV-Infected Drug Users : A Prospective, Randomized, Controlled Trial

BACKGROUND Directly administered antiretroviral therapy (DAART) is one approach to improve treatment adherence among human immunodeficiency virus (HIV)-infected drug users. METHODS In this randomized, controlled trial (ClinicalTrials.gov identifier, NCT00367172), the biological outcomes of a 6-month community intervention of DAART were compared with those of self-administered therapy among HIV-infected drug users. Patients randomized to receive DAART received supervised therapy 5 days per week from workers in a mobile health care van. The primary outcome, using an intention-to-treat approach, was the proportion of patients achieving either a reduction in HIV-1 RNA level of > or = 1.0 log10 copies/mL or an HIV-1 RNA level < or = 400 copies/mL at 6 months. Secondary outcomes included the mean change from baseline in HIV-1 RNA level and CD4+ T lymphocyte count. RESULTS Of the 141 patients who met the entry criteria, 88 were randomized to receive DAART, and 53 were randomized to receive self-administered therapy; 74 (84%) of 88 of the patients randomized to receive DAART accepted the intervention. Of the 74 patients who initiated DAART, 51 (69%) completed the full 6-month intervention. At the end of 6 months, a significantly greater proportion of the DAART group achieved the primary outcome (70.5% vs. 54.7; P=.02). Additionally, compared with patients receiving self-administered therapy, patients receiving DAART demonstrated a significantly greater mean reduction in HIV-1 RNA level (-1.16 log10 copies/mL vs. -0.29 log10 copies/mL; P=.03) and mean increase in CD4+ T lymphocyte count (+58.8 cells/microL vs. -24.0 cells/microL; P=.002). CONCLUSIONS This randomized, controlled trial was, to our knowledge, the first to demonstrate the effectiveness of DAART at improving 6-month virologic outcomes among drug users. These results suggest that DAART should be more widely available in HIV treatment programs that target drug users who have poor adherence to treatment.

Clinical Outcomes of Hepatitis C Treatment in a Prison Setting: Feasibility and Effectiveness for Challenging Treatment Populations

BACKGROUND More than one-third of people in the United States with hepatic C virus (HCV) infection pass through the correctional system annually. Data are lacking on outcomes of treatment with pegylated interferon plus ribavirin (PEG-RBV) in correctional settings. METHODS During 2002-2006, we analyzed patients in the Connecticut Department of Correction who received PEG-RBV. We assessed the rates of sustained virological response, hospitalization, and use of medications to treat psychiatric disorders and anemia. RESULTS Of 138 treatment-naive patients referred for treatment, 68 (49%) were approved. Overall, sustained virological response occurred in 47.1% of patients (for HCV genotype 1, 43.1%; for HCV genotypes 2 and 3, 58.8%). Only 9 patients (13%) discontinued treatment because of adverse effects. Multiple regression analysis revealed that not achieving a sustained virological response was correlated with HCV genotype 1 infection plus cirrhosis (adjusted odds ratio, 12.9; 95% confidence interval, 1.1-148) and baseline major depression (adjusted odds ratio, 3.4; 95% confidence interval, 1.01-11.6), but not with HIV infection, a baseline HCV RNA level >or=400,000 IU/mL, or black race. Compared with baseline, the rate of prescription of a new mood stabilizer (2.2 vs. 0.8 prescriptions per person-year) or an opioid (1.8 vs. 0.5 prescriptions per person-year) was higher during treatment, whereas there was no change in the rate of prescription of benzodiazepines and antipsychotic medications. CONCLUSIONS These results support the feasibility and clinical effectiveness of PEG-RBV for the treatment of chronic HCV infection in correctional facilities.

A prospective controlled trial of routine opt-out HIV testing in a men's jail.

Background Approximately 10 million Americans enter jails annually. The Centers for Disease Control and Prevention now recommends routine opt-out HIV testing in these settings. The logistics for performing routine opt-out HIV testing within jails, however, remain controversial. The objective of this study was to evaluate the optimal time to routinely HIV test newly incarcerated jail detainees using an opt-out strategy. Methods This prospective, controlled trial of routine opt-out HIV testing was conducted among 298 newly incarcerated male inmates in an urban mens jail in New Haven, Connecticut. 298 sequential entrants to the mens jail over a three week period in March and April 2008 were assigned to be offered routine opt-out HIV testing at one of three points after incarceration: immediate (same day, n = 103), early (next day, n = 98), or delayed (7 days, n = 97). The primary outcome was the proportion of men in each group consenting to testing. Results Routine opt-out HIV testing was significantly higher for the early (53%: AOR = 2.6; 95% CI = 1.5 to 4.7) and immediate (45%: AOR = 2.3; 95% CI = 1.3 to 4.0) testing groups compared to the delayed (33%) testing group. The immediate and early testing groups, however, did not significantly differ (p = 0.67). In multivariate analyses, factors significantly associated with routine opt-out HIV testing were assignment to the ‘early’ testing group (p = 0.0003) and low (bond ≥

Persistence of Virological Benefits Following Directly Administered Antiretroviral Therapy Among Drug Users: Results From a Randomized Controlled Trial

5,000, immigration or federal charges or pre-sentencing >30 days) likelihood of early release (p = 0.04). Two subjects received preliminary positive results and one of them was subsequently confirmed HIV seropositive. Conclusions In this mens jail where attrition was high, routine opt-out HIV testing was not only feasible, but resulted in the highest rates of HIV testing when performed within 24 hours of incarceration. Trial Registration ClinicalTrials.gov NCT00624247

Routine opt-out HIV testing strategies in a female jail setting: a prospective controlled trial.

Background:Although directly administered antiretroviral therapy (DAART) has demonstrated impressive biological benefits compared with self-administered therapy (SAT) among drug users, the persistence of DAART after transition to SAT has not been examined. Methods:We conducted a community-based, prospective, randomized controlled trial of 6 months of DAART compared with SAT. The primary outcome was the proportion of subjects who achieved virological success at 6 months postintervention, defined as either a 1.0 log10 reduction from baseline or HIV-1 RNA <400 copies per milliliter. Secondary outcomes included the change from baseline in HIV-1 RNA and CD4 lymphocyte count. Results:Of the 53 subjects in the SAT arm and 88 subjects in the DAART arm, 52 and 82, respectively, provided blood samples at 6 months postintervention. The DAART (n = 88) and SAT (n = 53) arms did not differ on virological success (DAART 58.0% vs. SAT 56.6%, P = 0.64), mean reduction in log10 HIV-1 RNA (−0.79 vs. −0.31 log10 copies/mL, P = 0.53), or mean change in CD4 lymphocyte count (+60.2 vs. −15.4 cells/mL, P = 0.12). In the multivariate analysis, only high levels of social support significantly predicted virological success. Conclusions:This analysis, from the first randomized controlled trial of DAART among active drug users, failed to show the persistence of the DAART intervention at improving virological outcomes. Additional strategies are needed to ensure the on-treatment benefits persist following the cessation of DAART.

Turning a blind eye: the mobilization of radiology services in resource-poor regions.

Background Ten million Americans enter jails annually. The objective was to evaluate new CDC guidelines for routine opt-out HIV testing and examine the optimal time to implement routine opt-out HIV testing among newly incarcerated jail detainees. Methods This prospective, controlled trial of routine opt-out HIV testing was conducted among 323 newly incarcerated female inmates in Connecticuts only womens jail. 323 sequential entrants to the womens jail over a five week period in August and September 2007 were assigned to be offered routine opt-out HIV testing at one of three points after incarceration: immediate (same day, n = 108), early (next day, n = 108), or delayed (7 days, n = 107). The primary outcome was the proportion of women in each group consenting to testing. Results Routine opt-out HIV testing was significantly highest (73%) among the early testing group compared to 55% for immediate and 50% for 7 days post-entry groups. Other factors significantly (p = 0.01) associated with being HIV tested were younger age and low likelihood of early release from jail based on bond value or type of charge for which women were arrested. Conclusions In this correctional facility, routine opt-out HIV testing in a jail setting was feasible, with highest rates of testing if performed the day after incarceration. Lower testing rates were seen with immediate testing, where there is a high prevalence of inability or unwillingness to test, and with delayed testing, where attrition from jail increases with each passing day. Trial Registration ClinicalTrials.gov NCT00624247

Initiation, Adherence, and Retention in a Randomized Controlled Trial of Directly Administered Antiretroviral Therapy

While primary care, obstetrical, and surgical services have started to expand in the worlds poorest regions, there is only sparse literature on the essential support systems that are required to make these operations function. Diagnostic imaging is critical to effective rural healthcare delivery, yet it has been severely neglected by the academic, public, and private sectors. Currently, a large portion of the worlds population lacks access to any form of diagnostic imaging. In this paper we argue that two primary imaging modalities--diagnostic ultrasound and X-Ray--are ideal for rural healthcare services and should be scaled-up in a rapid and standardized manner. Such machines, if designed for resource-poor settings, should a) be robust in harsh environmental conditions, b) function reliably in environments with unstable electricity, c) minimize radiation dangers to staff and patients, d) be operable by non-specialist providers, and e) produce high-quality images required for accurate diagnosis. Few manufacturers are producing ultrasound and X-Ray machines that meet the specifications needed for rural healthcare delivery in resource-poor regions. A coordinated effort is required to create demand sufficient for manufacturers to produce the desired machines and to ensure that the programs operating them are safe, effective, and financially feasible.

Directly administered antiretroviral therapy for HIV-infected drug users does not have an impact on antiretroviral resistance: results from a randomized controlled trial.

Directly administered antiretroviral therapy (DAART) can improve health outcomes among HIV-infected drug users. An understanding of the utilization of DAART—initiation, adherence, and retention—is critical to successful program design. Here, we use the Behavioral Model to assess the enabling, predisposing, and need factors impacting adherence in our randomized, controlled trial of DAART versus self-administered therapy (SAT) among 141 HIV-infected drug users. Of 88 participants randomized to DAART, 74 (84%) initiated treatment, and 51 (69%) of those who initiated were retained in the program throughout the entire six-month period. Mean adherence to directly observed visits was 73%, and the mean overall composite adherence score was 77%. These results were seen despite the finding that 75% of participants indicated that they would prefer to take their own medications. Major causes of DAART discontinuation included hospitalization, incarceration, and entry into drug-treatment programs. The presence of depression and the lack of willingness to travel greater than four blocks to receive DAART predicted time-to-discontinuation.

Crossing the quality chasm in resource-limited settings.

Background:Directly administered antiretroviral therapy (DAART) is an effective intervention that improves clinical outcomes among HIV-infected drug users. Its effects on antiretroviral drug resistance, however, are unknown. Methods:We conducted a community-based, prospective, randomized controlled trial of DAART compared with self-administered therapy (SAT). We performed a modified intention-to-treat analysis among 115 subjects who provided serum samples for HIV genotypic resistance testing at baseline and at follow-up. The main outcomes measures included total genotypic sensitivity score, future drug options, number of new drug resistance mutations (DRMs), and number of new major International AIDS Society (IAS) mutations. Results:The adjusted probability of developing at least 1 new DRM did not differ between the 2 arms (SAT: 0.41 per person-year [PPY], DAART: 0.49 PPY; adjusted relative risk [RR] = 1.04; P = 0.90), nor did the number of new mutations (SAT: 0.76 PPY, DAART: 0.83 PPY; adjusted RR = 0.99; P = 0.99) or the probability of developing new major IAS new drug mutations (SAT: 0.30 PPY, DAART: 0.33 PPY; adjusted RR = 1.12; P = 0.78). On measures of GSS and FDO, the 2 arms also did not differ. Conclusion:In this trial, DAART provided on-treatment virologic benefit for HIV-infected drug users without affecting the rate of development of antiretroviral medication resistance.

Strengthening Nepal's Female Community Health Volunteer network: a qualitative study of experiences at two years

Over the last decade, extensive scientific and policy innovations have begun to reduce the “quality chasm” - the gulf between best practices and actual implementation that exists in resource-rich medical settings. While limited data exist, this chasm is likely to be equally acute and deadly in resource-limited areas. While health systems have begun to be scaled up in impoverished areas, scale-up is just the foundation necessary to deliver effective healthcare to the poor. This perspective piece describes a vision for a global quality improvement movement in resource-limited areas. The following action items are a first step toward achieving this vision: 1) revise global health investment mechanisms to value quality; 2) enhance human resources for improving health systems quality; 3) scale up data capacity; 4) deepen community accountability and engagement initiatives; 5) implement evidence-based quality improvement programs; 6) develop an implementation science research agenda.