Duncan Smith-Rohrberg

Impact of Enhanced Services on Virologic Outcomes in a Directly Administered Antiretroviral Therapy Trial for HIV-Infected Drug Users

Background:Directly administered antiretroviral therapy (DAART) is a promising intervention for improving HIV outcomes among active drug users, but the elements associated with successful DAART programs remain largely unknown. This study aimed to assess the impact of colocated medical, case management, and referral to substance abuse services (DAART-Plus) among the subjects receiving DAART as part of a larger randomized controlled trial comparing DAART with self-administered therapy. Methods:The health services utilization of 72 subjects receiving DAART was analyzed for its impact on changes in HIV-1 RNA levels at 6 months. The primary outcome was virologic success, defined as achieving an HIV-1 RNA level ≤400 copies/mL or a ≥1.0 log10 reduction in HIV-1 RNA level. A second analysis consisted of linear regression assessing the effect of covariates on log10 HIV-1 RNA reduction from baseline to 6 months. Results:In multivariate analyses, achieving virologic success at 6 months was associated with high medical services utilization [adjusted odds ratio [AOR] = 10.0 (1.4, 73.9); P = 0.02] and with the use of case management services [AOR = 5.8 (1.1, 30.5); P = 0.04]. Both services resulted in a larger reduction in log10 HIV-1 RNA from baseline (difference in slopes: −0.9 and −1.0, respectively; P = 0.02 for both). Referral to off-site substance abuse services treatment did not significantly predict either virologic outcome. Conclusions:Among individuals who receive DAART, the utilization of on-site medical and case management services was independently associated with improved virologic outcomes. These results suggest the potential utility of integrating these services into DAART interventions (DAART-Plus) targeting HIV-infected drug users with problematic adherence.

The potential role of buprenorphine in the treatment of opioid dependence in HIV-infected individuals and in HIV infection prevention.

Untreated opioid dependence is a major obstacle to the successful treatment and prevention of human immunodeficiency virus (HIV) infection. In this review, we examine the interwoven epidemics of HIV infection and opioid dependence and the emerging role of buprenorphine in improving HIV treatment outcomes among infected individuals, as well as its role in primary and secondary prevention. This article addresses some of the emerging issues about integrating buprenorphine treatment into HIV clinical care settings and the various strategies that must be considered. Specifically, it addresses the role of buprenorphine in improving HIV treatment outcomes through engagement in care, access to antiretroviral therapy and preventive therapies for opportunistic infections, and the potential benefits of and pitfalls in integrating buprenorphine into HIV clinical care settings. We discuss the key research questions regarding buprenorphine in the area of improving HIV treatment outcomes and prevention, including a review of published studies of buprenorphine and antiretroviral treatment and currently ongoing studies, and provide insight into and models for integrating buprenorphine into HIV clinical care settings. Dialogue among practitioners and policy makers in the HIV care and substance abuse communities will facilitate an effective expansion of buprenorphine and ensure that these beneficial outcomes are achieved.

Research Note — Review of Corrections-Based Therapy for Opiate-Dependent Patients: Implications for Buprenorphine Treatment among Correctional Populations

Inmates with a history of opiate dependence represent a substantial proportion of the correctional population in the United States. Opiate use has negative consequences for both the inmate and society, including increased recidivism rates, increased infectious disease prevalence, avoidable emergency room use, decreased access to primary care services, and overdose. While there have been great successes in community-based treatment of opiate dependence, these successes have not yet been achieved in correctional settings. This paper reviews the pharmacological treatment options for opiate-dependent inmates, along with potential application for community-to-correctional approaches. The recent approval by the Food and Drug Administration (FDA) of physician-prescribed buprenorphine and the new opportunities it presents to corrections-based treatment are also explored in depth. Successful implementation of such strategies is likely to result in desirable health and social outcomes for both the inmate and the community at large.

Pharmacological Treatment of Substance Abuse in Correctional Facilities: Prospects and Barriers to Expanding Access to Evidence-Based Therapy

The individual and societal costs of untreated substance abuse are enormous. These costs include overuse of hospital emergency departments, death due to overdose, high unemployment, illegal activity, and incarceration (Mark, Woody, Juday, & Kleber, 2001; Wall et al., 2000). Substance users, especially injection drug users, tend to be among society’s most disease-burdened individuals, with a high prevalence of infectious diseases—HIV, hepatitis B and C, and tuberculosis (Edlin, 2002; Hagan et al., 2002; Kapadia et al., 2002; Martin, Cayla, Bolea, & Castilla, 2000; Spaulding, Greene, Davidson, Schneidermann, & Rich, 1999)—and comorbid psychiatric conditions (Milby et al., 1996). Throughout the 1980s, in an effort to combat the increasing prevalence of substance misuse, many state and federal governments enacted stringent antidrug laws. Largely as a result of these measures, incarceration rates in the United States have dramatically increased and have imposed pressures on a system ill-prepared to address the medical and social consequences of substance abuse (Pollack, Khoshnood, & Altice, 1999). According to the Bureau of Justice, 82% of jail inmates and 83% of state prisoners have a history of substance abuse; 64% and 70%, respectively, used drugs “regularly” (at least once a week for at least a month) in the period immediately preceding incarceration (Dunkle et al., 2004; Hammett, Harmon, & Rhodes, 2002). While the high rates of drug-related arrests, recidivism, and the large numbers of substance abusers within the correctional system are alarming, they also represent Chapter 23

Cytomegalovirus polyradiculopathy: a rare neurological manifestation of acquired immunodeficiency syndrome.

Sir, Polyradiculopathy is a rare but potentially devastating syndrome more common in Acquired Immunodeficiency Syndrome (AIDS). Although cytomegalovirus (CMV) is most commonly implicated, the differential diagnosis includes tuberculosis, syphilis, and lymphoma. We admitted a 36-year-old army truck driver from Haryana, India, HIV-positive since May 2004, with ascending, asymmetric flaccid paraplegia, lower extremity paraesthesia, and bladder and bowel retention since three months. His CD4 count was 4 cells/μl. He received intravenous (IV) immunoglobulin, oral Gancyclovir and highly active anti-retroviral therapy (HAART) comprising Zidovudine, Lamivudine, and Nevirapine, without improvement. On examination, all muscles of the lower extremity were hypotonic, wasted, with 0/5 strength, and absent deep tendon reflexes. Bulbocavernous and anal reflexes were absent. Light and deep touch sensations, nociception, proprioception, and vibration sense was all diminished bilaterally extending superiorly to approximately the L1 dermatome. Cerebrospinal fluid (CSF) showed 40 polymorphonuclear leukocytes per μl, 336 mg/dL protein, 90 mg/dL glucose (CSF: serum 62%), and negative on gram, India ink, and acid-fast bacilli staining. Suspecting polyradiculopathy due to cytomegalovirus or tuberculosis (TB), both intravenous Gancyclovir and anti-tuberculosis treatment (ATT) were initiated along with HAART. Magnetic resonance imaging (MRI) of the spinal cord showed confluent arachnoiditis of the cauda equine [Figure 1A]. CSF was sterile and CSF polymerase chain reaction (PCR) for mycobacterium and CMV were negative. Anti-CMV IgG was strongly positive in serum; blood testing for anti-CMV IgM, anti-HSV IgG/IgM, VDRL for syphilis, anti-toxoplasma IgG/IgM, HBsAg, and anti-HCV were all negative; CSF for antiCMV IgM/IgG, anti-HSV IgG/IgM, VDRL, and PCR for TB and CMV were negative. The patient gradually improved, and a repeat MRI after one month showed marked improvement in the confluent nerve roots [Figure 1B]. At three months follow-up, the patient was taken off Gancyclovir, and had recovered >50% of motor, sensory, and bladder and bowel function. He became ambulatory and tendon reflexes normalized. The final clinical impression was that of AIDS-related CMV polyradiculopathy that failed to respond to oral Gancyclovir but responded well to IV Gancyclovir and HAART. Polyradiculopathy in AIDS is a rare but devastating syndrome. This report, to the best of our knowledge, is the first such report from the Indian subcontinent. The differential diagnosis includes CMV,[1,2] tuberculosis, Varicella zoster virus, Ebstein Barr virus, Herpes simplex virus, syphilis, and lymphoma. CMV causes a subacute, progressive, asymmetric ascending paraplegia with urinary retention and sacral dysesthesias. Initial CSF examination in CMV may reveal the “classic” pattern of polymorphonuclear pleocytosis, elevated protein, and decreased glucose in only 50%. Nucleic acid amplification techniques are often rapid, sensitive, and specific, though expensive. In our case PCR for CMV was negative in CSF; although this test generally has sensitivity greater than 80%,[3] prior treatment decrease yield. Detection of CMV antigens (pp65) in CSF has a sensitivity of 91% and specificity approaching 100%.[4] Histopathological examination of the cauda equina roots shows polymorphonuclear or mononuclear Letters to Editor

Compromising comprehensive AIDS management will lead to failure.

Robert Colebunders and colleagues recently described an algorithm by which clinicians can monitor antiretroviral therapy efficacy in resource-limited settings. Through the algorithm which uses primarily clinical and immunological indicators to assess treatment failure the authors hope to better ration the use of viral load testing in developing countries. Although well-intentioned this algorithm may not achieve the clinical and epidemiological benefits that are necessary to tackle the AIDS pandemic. Without virological testing for treatment failure a physicians ability to avert drug resistance and mortality is severely compromised and this algorithm can do little to combat this fundamental reality. (excerpt)