Discontinuation of prophylaxis for HIV-associated opportunistic infections in the era of highly active antiretroviral therapy.

PURPOSE: The rationale for recent changes in guidelines for the prevention of opportunistic infections (OIs) in HIV-infected persons is discussed. SUMMARY: The epidemiology of AIDS has changed significantly since the advent of highly active antiretroviral therapy (HAART). Furthermore, the impact of HIV-associated OIs has decreased, leading to changes in the guidelines and recommendations for primary and secondary prophylaxis for such infections. While many patients can now be considered for discontinuation of suppressive therapy, clinical decision making surrounding the discontinuation of primary or secondary prophylaxis must take into account each patient's individual circumstances. Continued surveillance and careful monitoring of patients who stop prophylaxis will be critical to the overall success of OI treatment and prevention programs. CONCLUSION: The decision to discontinue primary or secondary prophylaxis for HIV associated OIs should be made on a case-by-case basis.

Pharmacokinetics of hydroxyurea in plasma and cerebrospinal fluid of HIV-1-infected patients.

Hydroxyurea has been shown to potentiate the activity of the antiretroviral nucleoside analogs. A significant complication of AIDS is invasion of the virus into the CNS, resulting in HIV-associated dementia (HAD). Because of the polar nature of these nucleosides and the presence of efflux pumps in the blood-brain barrier, only low CNS drug concentrations are achieved. Introduction of hydroxyurea into the CNS may therefore increase the antiviral activity of these drugs. This study evaluates the accessibility of hydroxyurea to the CNS following oral drug administration. Twelve HIV patients received 800 mg, 1000 mg, or 1200 mg oral hydroxyurea. Cerebrospinal fluid (CSF) and plasma drug concentrations were measured over 8 hours and simultaneously fitted to a pharmacokinetic model. It was determined that CSF hydroxyurea concentrations, corresponding to those found to increase antiretroviral nucleoside activity in vitro, were achieved.

Patterns of adherence to antiretroviral medications: the value of electronic monitoring.

OBJECTIVE: To investigate the patterns of intra-subject (between medication) adherence to antiretroviral therapy. DESIGN: A prospective, observational, 3-month study of adherence to antiretroviral therapy at an inner-city clinic in 40 HIV-infected subjects. METHODS: Adherence was monitored monthly by the use of medication event monitoring system (Aprex) caps placed on each antiretroviral drug in a subject's regimen. Agreement between different drug classes and dosing schedules, for each subject, was quantified by estimating the mean difference in adherence, with 95% limits of agreement. An analysis of variance model was used to estimate the variance of the differences. Individual dosing calendars were examined for each subject. RESULTS: The dosing schedule was a strong predictor of intra-subject adherence. Regardless of the subject's overall adherence rate, high or low, when subjects missed a dose of one medication, they missed a dose of both medications taken at that dosing time. Conversely, when medications were scheduled to be taken together, regardless of the drug class, the medications were taken at the same times. The majority of the subjects took medications at obviously incorrect times. Problematical adherence was related to thrice-daily dosing and food restrictions. CONCLUSION: This is the first report objectively to quantify intra-subject adherence to antiretroviral therapy and report the findings in detail. We observed clear patterns of drug-taking behavior among the subjects in our study. To the extent that medication scheduling is a controllable factor, our report provides an insight into specific patterns of behavior that may be targets for adherence counseling.