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Biomedical subjects

Frederick L Altice

Publications and source records attributed to Frederick L Altice.

17 recordsLinked to original sources

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.

Buprenorphine↗

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.

Adult↗

Pharmacokinetic drug interactions between opioid agonist therapy and antiretroviral medications: implications and management for clinical practice.

BACKGROUND: Opioid dependence and HIV/AIDS are 2 of the most serious yet treatable diseases worldwide. Global access to opioid agonist therapy and HIV treatment is expanding but when concurrently used, problematic pharmacokinetic drug interactions can occur. METHODS: We reviewed English, Spanish, French, and Italian language articles from 1966 to 2005 in Medline using the following keywords: HIV, AIDS, HIV therapy, antiretroviral therapy, HAART, drug interactions, methadone, and buprenorphine. Additionally, we reviewed abstracts from national and international meetings and conference proceedings. Selected references from these articles were reviewed as well. RESULTS: Clinical case series and carefully controlled pharmacokinetic interaction studies have been conducted between methadone and most approved antiretroviral therapies. Important pharmacokinetic drug interactions have been demonstrated within each class of agents, affecting either methadone or antiretroviral agents. Few studies, however, have been conducted with buprenorphine. The metabolism of both therapies, description of the known interactions, and clinical implications and management of these interactions are reviewed. CONCLUSIONS: Certain interactions between methadone and antiretroviral medications are known and may have important clinical consequences. To optimize care, clinicians must be alert to these interactions and have a basic knowledge regarding their management.

Acquired Immunodeficiency Syndrome↗

Models for integrating buprenorphine therapy into the primary HIV care setting.

Opiate dependence among human immunodeficiency virus (HIV)-infected patients has been associated with negative clinical outcomes, yet few affected patients receive appropriate and coordinated treatment for both conditions. The introduction of buprenorphine maintenance therapy into HIV care settings provides an opportunity for providers to integrate treatment for opiate dependence into their practices. Buprenorphine maintenance therapy has been associated with reductions in opiate use, increased social stability, improved adherence to antiretroviral therapy, and lowered rates of injection drug use. We describe the following 4 models for the integration of buprenorphine maintenance therapy into HIV care: (1) a primary care model, in which the highly active antiretroviral therapy-administering clinician also prescribes buprenorphine; (2) a model that relies on an on-site specialist in addiction medicine or psychiatry to prescribe the buprenorphine; (3) a hybrid model, in which an on-site specialist provides the induction (with or without stabilization phases) and the HIV care provider provides the maintenance phase; and (4) a drug treatment model that provides buprenorphine maintenance therapy services with HIV services in the substance abuse clinic setting. The key barriers against effective integration of buprenorphine maintenance therapy and primary HIV services are discussed, and we suggest several mechanisms to overcome such obstacles.

Anti-HIV Agents↗

Correlates of HIV infection among incarcerated women: implications for improving detection of HIV infection.

The prevalence of HIV infection in correctional settings is several-fold higher than found in community settings. New approaches to identifying HIV infection among prisoners are urgently needed. In order to determine the HIV seroprevalence and to identify the correlates of HIV infection among female prisoners, an anonymous, but linked HIV serosurvey was conducted at Connecticut's sole correctional facility for women (census=1,100). After removing all individual identifiers for inmates' standardized clinical and risk behavior information, data are linked by a third source to blinded HIV-testing information by a third party. This three-step sequential process allows for anonymous HIV testing that can still be linked with deidentified clinical and behavioral data. Of the 3,315 subjects with complete information, 250 (7.5%) were HIV+. Of these, 157 (63%) self-reported being HIV+. Using multiple logistic regression analysis, having sex with a known HIV+ person [adjusted odds ratio (AOR)=9.1] and injection drug use (AOR=6.1) were the most highly correlated risk factors for HIV, whereas leukopenia (AOR=9.4) and hypoalbuminemia (AOR=7.2) were the most significant laboratory markers. Other independent correlates of HIV included self-report of syphilis (AOR=1.9) or genital herpes infection (AOR=2.7) and being Black (AOR=2.1) or Hispanic (AOR=2.2). The prevalence of HIV and HIV-risk behaviors is high among incarcerated women. Existing voluntary HIV counseling and testing programs do not completely target high-risk groups who remain part of the evolving epidemic. Defined demographic, behavioral, and clinical assessments may provide useful information for encouraging targeted counseling and testing. Newer targeted approaches merit further study to determine the effectiveness of this approach. Alternative methods of facilitating more widespread HIV testing, such as saliva tests, rapid serologic tests, and more routine testing in high HIV-prevalence areas should be considered both for clinical and for public health benefits.

AIDS Serodiagnosis↗

Adherence to hepatitis B virus vaccination at syringe exchange sites.

Injection drug users (IDUs) are at high risk for hepatitis B virus (HBV); however, they often do not receive preventive vaccination. IDUs who use mobile health care services linked to a syringe exchange program in New Haven were routinely screened for HBV, hepatitis C virus, and syphilis. Individuals without prior exposure to HBV were offered three-part vaccination series. Of the 212 IDUs screened for HBV infection, 134 (63%) were eligible (negative for HBV surface and core anti-bodies) for vaccination and 10 (4.7%) had evidence of chronic HBV infection. Compared to those with previous exposure to HBV, vaccine-eligible patients were significantly more likely to be younger and use heroin and less likely to be black, home-less, daily injectors, and cocaine users. Of the 134 vaccine-eligible subjects, 103 (77%) and 89 (66%) completed two and three vaccinations, respectively. Correlates of completing all three vaccinations included older age (OR = 1.06, 95% CI = 1.04-1.07), injecting daily (OR = 2.12, 95% CI = 1.36-6.73), and being homeless (OR = 1.98, 95% CI = 1.14-12.27). These results suggest that IDUs remain at high risk for acquiring HBV infection. Programs that link health care to a syringe exchange program are effective ways to provide preventive health care services to IDUs, particularly HBV vaccination. Trust engendered by and mutual respect afforded by such programs result in repeated encounters by active IDUs over time.

Adult↗

Cost-effectiveness of HIV screening for incarcerated pregnant women.

Antiretroviral therapy (ART) initiated on a prenatal basis in HIV-infected pregnant women is a highly effective method for preventing mother-to-child HIV transmission. We developed a decision analytic model to project the clinical and economic outcomes of alternative HIV screening strategies (voluntary prenatal screening [VPS], routine prenatal screening [RPS], and mandatory newborn screening [MNS]) for a high-risk population of incarcerated pregnant women. Data for the decision model came from the HIV voluntary counseling and testing program at Connecticut's sole correctional facility for women and a comprehensive anonymously linked serosurvey of all inmates who entered the facility during the 2-year period beginning in October 1994. Based on serosurvey results, in the absence of any HIV screening program, 2.5 cases of pediatric HIV infection would be expected per 1000 pregnancies. Multiplied by the discounted lifetime cost per case of $247,000, this translates to a cost of $624 per testing-eligible prison entrant. Entrants were considered eligible if they were pregnant and their HIV status was unknown. MNS would save money, cost $364 per eligible entrant, and simultaneously reduce the rate of infections to 1.1 per 1000 pregnancies. Doing both MNS and RPS is most effective in reducing the rate of new infections (down to 0.2 per 1000 pregnancies). It would, however, increase costs to $430 per eligible entrant. This would result in an incremental cost of $73,603 per additional pediatric HIV case averted when compared with MNS alone. If mandatory newborn testing was not considered a feasible option, RPS would dominate VPS and would be cost-saving compared with no screening. RPS compares favorably with alternative uses of HIV prevention and treatment resources. In correctional facilities where voluntary newborn screening is already in place, our findings show that there remains a small marginal benefit to be realized from switching to RPS. In settings where HIV screening policies are not in place, however, the implementation of RPS can be expected to significantly reduce pediatric HIV cases and net health care expenditures.

Adult↗

Managing HIV/AIDS in correctional settings.

Approximately one quarter of people living with HIV/AIDS in the United States pass through the correctional system, resulting in a burden of infection on the correctional health care system that has challenged correctional and public health officials. The HIV epidemic behind bars results from the high prevalence of HIV risk behaviors among those incarcerated: illicit drug use, untreated mental illness, prostitution, homelessness, and poverty. Challenges to HIV care in correctional settings include management of comorbid conditions, remoteness from HIV care sites, organizational constraints, and access to effective therapies. Despite these challenges, prisoners with HIV have derived considerable benefit from HIV detection and treatment. In order to achieve parity in HIV outcomes among vulnerable populations, effective prison-release programs that incorporate effective case management with effective drug treatment and adherence strategies are required to extend the benefit of highly active antiretroviral therapy as prisoners transition back to community settings.

Antiretroviral Therapy, Highly Active↗

Developing a directly administered antiretroviral therapy intervention for HIV-infected drug users: implications for program replication.

Directly administered antiretroviral therapy (DAART) is one approach to improving adherence to among human immunodeficiency virus (HIV)-infected drug users. We evaluated the essential features of a community-based DAART intervention in a randomized, controlled trial of DAART versus self-administered therapy. Of the initial 72 subjects, 78% were racial minorities, and 32% were women. Social and medical comorbidities among subjects included homelessness (35% of subjects), lack of interpersonal support (86%), major depression (57%), and alcoholism (36%). At baseline, the median CD4+ cell count was 403 cells/mL and the median HIV-1 RNA load was 146,333 copies/mL (log10 5.31 copies/mL). During the prior 6 months, 33% of subjects had missed a medical appointment, and 47% had visited an emergency department. Although most subjects (67%) preferred to take their own medications, 76% would accept DAART if it were made compulsory. A methadone clinic was the DAART venue acceptable to the fewest subjects (36%), and a mobile syringe-exchange program was acceptable to the most subjects (83%). Adherence was higher for supervised than for unsupervised medication administration (P<.0001), a finding that supports use of daily supervision of once-daily regimens. Moreover, DAART should incorporate enhanced elements such as convenience, flexibility, confidentiality, cues and reminders, responsive pharmacy and medical services, and specialized training for staff.

Adult↗

Effectiveness of antiretroviral therapy among HIV-infected prisoners: reincarceration and the lack of sustained benefit after release to the community.

Responses to highly active antiretroviral therapy (HAART) in correctional settings and their sustained benefit in prisoners after release are currently not known. To examine the human immunodeficiency virus type 1 (HIV-1) RNA level (VL) and CD4 lymphocyte response to HAART during incarceration and upon reentry to the correctional system, we conducted a retrospective cohort study of longitudinally linked demographic, pharmacy, and laboratory data from the Connecticut prison system. During incarceration, the mean CD4 lymphocyte count increased by 74 lymphocytes/ mu L, and the mean VL decreased by 0.93 log10 copies/mL (P<.0001). Fifty-nine percent of the subjects achieved a VL of <400 copies/mL at the end of each incarceration period. For the 27% of subjects who were reincarcerated, the mean CD4 lymphocyte count decreased by 80 lymphocytes/ mu L, and the mean VL increased by 1.14 log10 (P<.0001). Although HAART use resulted in impressive VL and CD4 lymphocyte outcomes during the period of incarceration, recidivism to prison was high and was associated with a poor outcome. More effective community-release programs are needed for incarcerated patients with HIV disease.

Antiretroviral Therapy, Highly Active↗

Human immunodeficiency virus infection with human granulocytic ehrlichiosis complicated by symptomatic lactic acidosis.

Lactic acidosis has been reported as a complication associated with antiretroviral therapy; in particular, usually with use of nucleoside reverse-transcriptase inhibitors. We describe a human immunodeficiency virus (HIV)-infected patient with a history of lipodystrophy who presented with hepatic insult associated with documented human granulocytic ehrlichiosis (HGE). Despite a normal serum lactate level before the onset of acute coinfection, the patient developed symptomatic hyperlactatemia while receiving appropriate treatment for HGE. To date, this is the first presentation of symptomatic hyperlactatemia in a patient with HIV infection and HGE.

Acidosis, Lactic↗

Pilot study to enhance HIV care using needle exchange-based health services for out-of-treatment injecting drug users.

The introduction of highly active antiretroviral therapy (HAART) has resulted in marked reductions in mortality and acquired immunodeficiency syndrome (AIDS) incidence across all risk groups; however, the proportionate decrease among injecting drug users (IDUs) has been less impressive. Much of the disparity in benefit to IDUs has been a consequence of decreased access to and receipt of potent antiretroviral combinations. Strategies to increase access to and utilization of HAART have included entry into drug treatment and abstinence. Unfortunately, as few as 15%-20% of active drug users in the United States, and in many other countries, are in drug treatment at any one time. We report a pilot project among out-of-drug treatment IDUs infected with human immunodeficiency virus (HIV); HIV therapy was successfully provided to active heroin injectors using the Community Health Care Van (CHCV) at sites of needle exchange. Subjects were willing to initiate, but were not receiving, recommended HIV therapy and were not interested in formal drug treatment. Antiretroviral therapy regimens were selected and linked to heroin injection timing. Weekly visits were scheduled by CHCV staff to assess adverse side effects and encourage adherence. Of the 13 participants, the mean baseline HIV-1 RNA level and CD4 lymphocyte count were 162,369 (log 5.21) copies per milliliter and 265 cells per milliliter, respectively. By 6 months, the proportion whose HIV-1 RNA was below the limits of detection (<400 copies/mL) was 85% (N=11); 77% (N=10) had nondetectable levels by 9 months. By 12 months, 54% (N=7) had a persistently nondetectable viral load, and the net increase in CD4 lymphocyte count was 150 cells per milliliter. As an additional and unintended benefit of this pilot project, 9 (69%) subjects chose to enter drug treatment after achieving a nondetectable viral load. Entry into drug treatment was associated with durability of viral suppression. This small pilot study suggests that health services based on needle exchange may enhance access to HAART among out-of-treatment HIV-infected IDUs. In addition, it demonstrates that this population can benefit from this therapy with the support of a nontraditional, community-based health intervention.

Adult↗

Increasing drug users' adherence to HIV treatment: results of a peer-driven intervention feasibility study.

Active drug users with HIV infection suffer from both low utilization of, and adherence to, primary care. Combining drug treatment and primary care on-site reduces these problems significantly because it creates a social support structure; treatment program staffs can monitor patients' adherence and provide ongoing encouragement. But in the United States, only a very small minority of HIV + drug users receive this demonstrably effective form of care. We report the results from a feasibility study of an alternative support structure, termed a "peer-driven intervention", that serves as a functional equivalent to drug treatment for increasing drug users' adherence to HIV therapeutics. The six-month study included 14 adult active drug users receiving medical care for HIV disease in New Haven, Connecticut. As a health advocate, each subject was assigned and asked to meet with another subject once a week at the project's storefront to provide peer support and counseling. As a peer, each subject was assigned and asked to meet with another health advocate once a week to receive support in keeping up his or her medical care. No two subjects played both roles for one another. Advocates earned nominal monetary rewards for eliciting positive responses from their peers in keeping clinical appointments, responding to physicians' referrals, picking up prescriptions on time and attending weekly meetings with the advocate. The results of the study suggest that an alternative social support structure to drug treatment is feasible for increasing active drug users' adherence to medical care. Innovative mechanisms that harness drug users' peer pressure to promote positive behavioral changes deserve greater study.

Acquired Immunodeficiency Syndrome↗

The impact of needle exchange-based health services on emergency department use.

OBJECTIVE: To examine the impact of the New Haven Community Health Care Van (CHCV), a mobile needle exchange-based health care delivery system, in reducing emergency department (ED) use among out-of-treatment injection drug users (IDUs) between January 1, 1996 and December 31, 1998. DESIGN: A pre-post comparison of ED utilization was performed using linked medical records from New Haven's only two emergency departments. Fixed-effect negative binomial regression analysis was used to explore the impact of the CHCV on ED use within a longitudinal cohort. SETTING: Mobile health clinic in New Haven, Conn. PARTICIPANTS: Out-of-treatment IDUs. INTERVENTION: Acute care, linkages to medical, drug treatment, and social services. MEASUREMENTS AND MAIN RESULTS: Among 373 IDUs, 117 (31%) were CHCV clients, and 256 had not used CHCV services. At baseline, CHCV users were more frequent users of ED services (P <.001). After full-scale implementation, mean ED utilization declined among CHCV clients and increased within the non-CHCV group. CHCV use is associated with statistically significant reductions in ED use, with an incidence rate ratio (IRR) of 0.79 (95% confidence interval [95% CI], 0.66 to 0.95). Subgroup analyses demonstrated significant IRR reductions, notably among Hispanics (0.65; 95% CI, 0.47 to 0.90), men (0.79; 95% CI, 0.64 to 0.98], HIV-negative IDUs (0.79; 95% CI, 0.63 to 0.98), and those with mental illness (0.75; 95% CI, 0.60 to 0.94). CONCLUSION: Needle exchange-based health care services can reduce ED utilization among high-risk injection drug users. Such services may have an important role within communities with high rates of drug use and HIV/AIDS.

Connecticut↗