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Biomedical subjects

G H Friedland

Publications and source records attributed to G H Friedland.

At least 19 recordsLinked to original sources

Trust and the acceptance of and adherence to antiretroviral therapy.

BACKGROUND: Antiretroviral therapy (ART) has resulted in reduced AIDS incidence and mortality. Socially marginalized individuals with HIV infection, particularly injection drug users (IDUs), have received less ART and derived less benefit than others. Little is known about the therapeutic process necessary to promote acceptance of and adherence to ART among marginalized HIV-infected populations. We report on the correlates of both acceptance of and adherence to ART among HIV infected prisoners, most of whom are IDUs. DESIGN: Using a cross-sectional survey design within four ambulatory prison HIV clinics, 205 HIV-infected prisoners eligible for ART were recruited between March and October 1996. MEASUREMENTS: Detailed interviews were conducted that included personal characteristics, health status and beliefs, and validated standardized scales measuring depression, health locus of control, social desirability and trust in physician, medical institutions and society. Acceptance and adherence were documented by self-report and validated for a subset by pharmacy review. Clinical information was obtained from standardized chart review. Adherence was defined as having taken > or = 80% of ART. RESULTS: The acceptance of (80%) and adherence to (84%) ART among this group of prisoners was high. Multiple regression models demonstrated that correlates of acceptance of and adherence to ART differed. Acceptance was associated with trust in physician (8% increase for each unit increase with trust in physician scale) and trust in HIV medications (threefold reduction for those mistrustful of medication). Side effects (OR = 0.09), social isolation (OR = 0.08), and complexity of the antiretroviral regimen (OR = 0.33) were associated with decreased adherence. The prevalence of health beliefs suggesting an adverse relationship between ART and drugs of abuse was high (range 59 to 77%). Adherence did not differ among those receiving directly observed therapy (82%) or self-administration (85%). CONCLUSIONS: ART can be successfully administered within a correctional setting. Trust and the therapeutic relationship between patient and physician remain central in the ART initiation process. Characteristics of the therapeutic agents and the degree of social isolation predict adherence. These results may inform the design of interventions to improve both acceptance of and adherence to ART particularly among marginalized populations who have not derived full benefit from these potent new therapies.

Adult↗

Public health consequences of screening patients for adherence to highly active antiretroviral therapy.

Improvements in HIV antiretroviral therapy (ART) have been accompanied by increasing recognition of the importance of adherence to treatment regimens for maximizing patient benefits while minimizing the emergence of drug-resistant virus. Whether clinicians should screen patients for adherence and only administer therapy to those believed likely to adhere has not been resolved. We first examine the implications of data drawn from a recent study reporting physicians' ability to predict whether patients will adhere to highly active antiretroviral therapy (HAART) or not. We then extend previously developed mathematical models of ART to include screening for adherence and focus on resulting drug resistance as well as on HIV and AIDS incidence at the population level. We show that although screening for adherence is likely to reduce the level of drug resistance compared with a policy of treating all HIV patients with HAART, rates of new HIV infections and AIDS cases in the population would likely increase unless screening accuracy is extremely (perhaps implausibly) high.

Acquired Immunodeficiency Syndrome↗

In vivo antagonism with zidovudine plus stavudine combination therapy.

Human immunodeficiency virus (HIV)-infected subjects receiving zidovudine were randomized either to add stavudine (d4T) or didanosine (ddI) to their current regimen or to switch to ddI or d4T monotherapy. After 16 weeks of therapy, the mean reduction in HIV RNA from baseline was 0.14 log(10) copies/mL in patients receiving d4T or zidovudine plus d4T. In subjects receiving ddI or ddI plus zidovudine, reductions were 0.39 and 0.56 log(10), respectively. CD4 cell counts remained stable or showed modest increases in all arms except the zidovudine plus d4T arm. Patients receiving zidovudine plus d4T showed progressive declines in CD4 cell counts with a median of 22 cells/mm(3) below baseline by 16 weeks. Examination of intracellular levels of d4T-triphosphate in 6 subjects was consistent with previous in vitro studies demonstrating pharmacologic antagonism between zidovudine and d4T. Analysis of these data suggests that zidovudine and d4T should not be prescribed in combination and that ddI provides greater antiviral activity than d4T in zidovudine-treated patients.

Adult↗

Breaking the silence.

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Acquired Immunodeficiency Syndrome↗

Efficacy and safety of delavirdine mesylate with zidovudine and didanosine compared with two-drug combinations of these agents in persons with HIV disease with CD4 counts of 100 to 500 cells/mm3 (ACTG 261). ACTG 261 Team.

To evaluate the antiretroviral activity of delavirdine mesylate, a non-nucleoside reverse transcriptase inhibitor of HIV-1, we performed a phase II, randomized, double-blind, multicenter trial comparing the three-drug combination of delavirdine with zidovudine and didanosine to two-drug combinations of these drugs. Patients with CD4 cell counts between 100 and 500 cells/mm3 without prior or <6 months of monotherapy with zidovudine or didanosine were randomized to one of four arms and observed on a follow-up basis for 48 weeks. In total, 544 patients were evaluated. In those assigned to the three-drug regimen, mean short-term (weeks 4-12) and long-term (weeks 40-48) change in CD4 cells from baseline were 49.3+/-8.1 and 65.4+/-13.4 cells/mm3, respectively; mean short-term and long-term HIV-1 RNA changes from baseline were -1.13 log10+/-0.12 and -0.73+/-0.12 copies/ml, respectively. These responses in CD4 cell counts and HIV-1 RNA levels were better in comparisons with each of the two-drug arms at all study points; however, differences were not consistently significant. Gastrointestinal side effects were experienced by 33% of patients (178 of 544), and 30% (121 of 407) receiving delavirdine experienced rash, only one case of which was severe. In this study, therapy with delavirdine + zidovudine + didanosine was safe and showed modest, but not always significant, antiviral activity and CD4 cell count benefit compared with two-drug regimens with these agents. Key

Adult↗

Nevirapine induced opiate withdrawal among injection drug users with HIV infection receiving methadone.

BACKGROUND: Pharmacokinetic interactions complicate and potentially compromise the use of antiretroviral and other HIV therapeutic agents in patients with HIV disease. This may be particularly so among those receiving treatment for substance abuse. OBJECTIVE: We describe seven cases of opiate withdrawal among patients receiving chronic methadone maintenance therapy following initiation of therapy with the non-nucleoside reverse transcriptase inhibitor, nevirapine. DESIGN: Retrospective chart review. RESULTS: In all seven patients, due to the lack of prior information regarding a significant pharmacokinetic interaction between these agents, the possibility of opiate withdrawal was not anticipated. Three patients, for whom methadone levels were available at the time of development of opiate withdrawal symptoms, had subtherapeutic methadone levels. In each case, a marked escalation in methadone dose was required to counteract the development of withdrawal symptoms and allow continuation of antiretroviral therapy. Three patients continued nevirapine with methadone administered at an increased dose; however, four chose to discontinue nevirapine. CONCLUSION: To maximize HIV therapeutic benefit among opiate users, information is needed about pharmacokinetic interactions between antiretrovirals and therapies for substance abuse.

Adult↗

Attaining higher goals in HIV treatment: the central importance of adherence.

In recent years, advances in HIV therapeutics have changed the nature of HIV/AIDS disease, so that it has now assumed some of the characteristics of a 'chronic' disease. Several factors have, however, qualified these advances. Social, economic, and clinical variables have confounded universal therapeutic success. Access to the highly active antiretroviral therapy is limited among marginalized populations, such as the homeless, or absent in many nations that have poor resources. In addition, study populations are often not fully representative of those actually cared for in clinical practice, who may respond differently to the study medications. Moreover, physiologic differences between patients may alter drug plasma levels, resulting in varying efficacy levels in different patients. Finally, and crucial among determinants of effective therapy, is a patient's level of adherence to the antiretroviral regimen. The magnitude of 'error-prone' viral replication makes resistance to antiretroviral agents invariable. In the presence of partially suppressive therapy, viral replication will select for viral variants with resistance mutations. Therefore, potent and continuous suppressive therapy for the duration of viral replicative capability is necessary for therapy to be effective. Factors that have an impact on adherence include characteristics of the treatment regimen, of patients and clinicians, and of the clinical setting. Successful adherence to therapeutic regimens is the responsibility of clinicians as well as patients. Many patient- and clinician-focused strategies and interventions that can improve adherence exist. The simplification of current antiviral regimens, without the loss of potency, is essential to achieving the goal of complete adherence. Maximizing the long-term benefit of highly active antiretroviral therapy requires knowledge of the technical and biologic aspects of HIV therapeutics, but necessitates an understanding of the behavioral aspects of therapeutics as well.

Anti-HIV Agents↗

A prospective study of syphilis and HIV infection among injection drug users receiving methadone in the Bronx, NY.

OBJECTIVES: The purpose of this study was to assess the relationship between syphilis and human immunodeficiency virus (HIV) infection in injection drug users. METHODS: A 6-year prospective study of 790 injection drug users receiving methadone maintenance treatment in the Bronx, NY, was conducted. RESULTS: Sixteen percent (4/25) of HIV-seroconverting patients, 4.8% (16/335) of prevalent HIV-seropositive patients, and 3.5% (15/430) of persistently HIV-seronegative patients was diagnosed with syphilis. Incidence rates for early syphilis (cases per 1000 person-years) were 15.9 for HIV-seroconverting patients, 8.9 for prevalent HIV-seropositive patients, and 2.9 for persistently HIV-seronegative patients. Early syphilis incidence was higher among women than men (8.4 vs 3.2 cases per 1000 person-years). Independent risks for early syphilis included multiple sex partners, HIV seroconversion, paid sex, and young age. All HIV seroconverters with syphilis were female. CONCLUSIONS: Diagnosis of syphilis in drug-using women reflects high-risk sexual activity and is associated with acquiring HIV infection. Interventions to reduce the risk of sexually acquired infections are urgently needed among female drug users.

Adolescent↗

Heroin use during methadone maintenance treatment: the importance of methadone dose and cocaine use.

OBJECTIVES: The purpose of this study was to examine factors associated with heroin use during methadone maintenance treatment. METHODS: Logistic regression statistical models were used to examine data obtained in a cross-sectional sample of 652 methadone patients. RESULTS: Heroin use during the 3 months prior to interview was shown to be greatest among (1) patients maintained on methadone dosages of less than 70 mg/day (adjusted odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.3, 3.4) and (2) patients who used cocaine during treatment (adjusted OR = 5.9, 95% CI = 3.8, 9.1). These results were independent of treatment duration, treatment compliance, alcohol use, and socioeconomic factors. Cocaine users were more likely than nonusers of cocaine to use heroin at all methadone dosage levels. CONCLUSIONS: This study confirms and extends past research showing high-dose methadone maintenance to be important to heroin abstinence. Further investigation of the independent association between heroin use and cocaine use is needed.

Adult↗