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- Mukonzo, Jackson K, et al.
(författare)
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HIV/AIDS Patients Display Lower Relative Bioavailability of Efavirenz than Healthy Subjects.
- 2011
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Ingår i: Clinical pharmacokinetics. - : Springer Science and Business Media LLC. - 0312-5963 .- 1179-1926. ; 50:8, s. 531-40
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pharmacokinetic studies of antiretroviral drugs are often conducted in adult healthy subjects, and the results are extrapolated to HIV/AIDS patients. HIV/AIDS, however, is known to cause morphological and physiological changes that may alter the pharmacokinetics of antiretroviral drugs. We examined the effect of HIV/AIDS on the pharmacokinetics of efavirenz in Ugandans. Methods: After a first oral dose of efavirenz 600 mg in treatment-naïve HIV-infected patients, blood samples were collected at nine time points up to 24 hours. The plasma-concentration time data from these patients were merged with previously reported data from adult healthy subjects. Population pharmacokinetic models were fitted to the data, using NONMEM VI software. Covariate analyses were performed to estimate the effects of HIV/AIDS disease, demographic characteristics (sex, bodyweight, age), biochemical variables (serum creatinine, urea, alanine aminotransferase) and pharmacogenetic variation in cytochrome P450 (CYP) 2B6, CYP3A5 and adenosine triphosphate-binding cassette, sub-family B, member 1 (ABCB1) on the population pharmacokinetic parameters. Results: Efavirenz plasma concentration-time data obtained from 29 HIV-1-infected, treatment-naïve patients were merged with previously reported data from 32 adult healthy subjects. The model identified sex and HIV/AIDS disease as statistically significant categorical predictors of efavirenz pharmacokinetics. Females were predicted to have a 2-fold higher volume of distribution of the peripheral compartment after oral administration (V(2)/F) than males (95% CI 1.53, 2.63), while HIV/AIDS patients were found to have 30% lower relative bioavailability (95% CI 18.7, 40.7) than healthy subjects. The increased V(2)/F in females resulted in a 2-fold longer elimination half-life than in males. Conclusion: On the basis of the findings of this analysis, we conclude that, apart from bodyweight-based differences, both HIV/AIDS disease and sex affect efavirenz pharmacokinetics in Ugandans. HIV/AIDS disease is associated with reduced relative bioavailability of efavirenz. We recommend that findings from healthy subject studies be confirmed in HIV/AIDS patients and that caution be applied in direct extrapolation of exposure data to the target patient population.
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| 2. |
- Obua, Celestino, et al.
(författare)
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Multiple ART Programs Create a Dilemma for Providers to Monitor ARV Adherence in Uganda
- 2011
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Ingår i: Open AIDS Journal. - : Bentham Science Publishers Ltd.. - 1874-6136. ; 5, s. 17-24
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Tidskriftsartikel (refereegranskat)abstract
- Background: Increased availability and accessibility of antiretroviral therapy (ART) has improved the length and quality of life amongst people living with HIV/AIDS. This has changed the landscape for care from episodic to longterm care that requires more monitoring of adherence. This has led to increased demand on human resources, a major problem for most ART programs. This paper presents experiences and perspectives of providersin ART facilities, exploring the organizational factors affecting their capacity to monitor adherence to ARVs. Methods: From an earlier survey to test adherence indicators and rank facilities as good, medium or poor adherence performances, six facilities were randomly selected, two from each rank. Observations on facility set-up, provider-patient interactions and key informant interviews were carried out. The strengths, weaknesses, opportunities and threats identified by health workers as facilitators or barriers to their capacity to monitor adherence to ARVs were explored during group discussions. Results: Findings show that the performance levels of the facilities were characterized by four different organizational ARTprograms operating in Uganda, with apparent lack of integration and coordination at the facilities. Of the six facilities studied, the two highadherence performing facilities were Non-Governmental Organization (NGO) programs, while facilities with dual organizational programs(Governmental/NGO) performed poorly. Working conditions, record keeping and the duality of programs underscored the providers' capacity tomonitor adherence. Overall 70% of the observed provider-patient interactions were conducted in environments that ensured privacy of the patient. The mean performance for record keeping was 79% and 50% in the high and low performing facilities respectively. Providers often found it difficult to monitor adherence due to the conflicting demands from the different organizational ART programs. Conclusion: Organizational duality at facilities is a major factor in poor adherence monitoring. The different ART programs in Uganda need to be coordinated and integrated into a single well resourced program to improve ART services and adherence monitoring. The focus on long-term care of patients on ART requires that the limitations to providers' capacity for monitoring adherence become central during the planning and implementation of ART programs.
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