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Karen M Megazzini,
Moses Sinkala,
Sten H Vermund,
David T Redden,
Daniel W Krebs, Edward P Acosta,
Joyce Mwanza,
Robert L Goldenberg,
Namwinga Chintu,
Marc Bulterys,
Jeffrey Sa Stringer
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ABSTRACT: Determine whether enhanced labor ward-based services for prevention of mother-to-child transmission of HIV (PMTCT) would improve nevirapine (NVP) coverage.
Cluster-randomized trial at 12 public-sector delivery centers in Lusaka, Zambia.
Following a baseline surveillance period, 12 labor wards were randomized, six to offer opt-in HIV testing to women of unknown serostatus (with NVP administration as indicated) and to assess NVP adherence among known HIV-infected women. The six control labor wards provided the standard of care. The NVP coverage endpoint was defined as the proportion of HIV-infected/exposed women/infant pairs with confirmed NVP ingestion. We used generalized estimating equations (GEE) to determine the odds of coverage associated with the intervention and ultimately used the parameters for the estimated GEE model to estimate relative risk.
Between October 2005 and January 2006, 7664 women gave birth at participating clinics. We collected anonymous-linked blood from 7592 (99%) umbilical cords; tested 7438 (97%) for HIV, 1618 (22%) were seropositive, and of these, 1279 (79%) were tested for NVP. At baseline (preintervention), the probability of HIV-infected/exposed women/infant pairs receiving NVP in treatment clinics (42%) was 0.89 times the probability of being covered in control clinics (53%) whereas during the intervention period the probability of treatment clinic coverage (52%) was 1.22 the probability control clinic coverage (43%), representing a multiplicative effect of 1.37 upon the RR at baseline (ratio of relative risks 1.37, bootstrapped 95% CI, 1.04-1.77).
Labor ward-based PMTCT programs are feasible and can have a significant, positive impact on NVP coverage.
AIDS (London, England) 11/2009; 24(3):447-55. · 4.91 Impact Factor
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ABSTRACT: The biggest challenge facing highly antiretroviral-experienced patients and their caregivers is the diminishing number of therapeutic options available that sustain activity despite increasing numbers of drug-resistance mutations. New options in antiretroviral treatment have been introduced: two new members of traditional antiretroviral classes (darunavir and etravirine) and two drugs with novel mechanisms of action (raltegravir and maraviroc). Each was approved for use in treatment-experienced patients. A fifth drug-containing efavirenz, tenofovir, and emtricitabine (Atripla; Bristol-Myers Squibb, New York, NY, and Gilead Sciences, Foster City, CA)-is a novel coformulation of existing drugs from two different classes, simplifying administration with the intent of increasing adherence. Because successful management of HIV infection requires the simultaneous use of three or more drugs, understanding the pharmacologic aspects of coadministration is critical. This review summarizes the pharmacokinetic properties affecting the administration of these recently approved drugs in light of highly active antiretroviral treatment guidelines.
Current HIV/AIDS Reports 03/2009; 6(1):43-50.
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David W Haas,
Susan L Koletar,
Laura Laughlin,
Michelle A Kendall,
Carol Suckow,
John G Gerber,
Andrew R Zolopa,
Richard Bertz,
Michael J Child,
Lara Hosey,
Beverly Alston-Smith, Edward P Acosta
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ABSTRACT: Rifampin is the cornerstone of antituberculosis therapy, but induction of hepatic cytochrome P4503A by rifampin markedly lowers HIV protease inhibitor plasma concentrations.
This phase 1, open-label, one-arm study was designed to assess pharmacokinetic interactions and safety of atazanavir, ritonavir, and rifampin among 14 evaluable HIV-seronegative volunteers. The study included 3 sequential periods of study drug dosing, with plasma sampling for pharmacokinetic analyses to occur on the last day of each period. During period 1, participants received rifampin 600 mg every 24 hours for 8 days. During period 2, participants continued rifampin 600 mg every 24 hours, and added atazanavir 300 mg and ritonavir 100 mg every 12 hours, to continue for at least 11 days. During period 3, atazanavir was to be increased to 400 mg every 12 hours.
Upon adding atazanavir and ritonavir, the first 3 subjects developed vomiting and transaminase elevations resulting in study drug discontinuation. The study was therefore terminated.
Coadministration of rifampin with HIV protease inhibitors may not be a viable treatment option if rifampin administration precedes protease inhibitor initiation. Future studies, which explore concomitant HIV protease inhibitors with rifampin must carefully consider the sequence in which drugs are initiated.
JAIDS Journal of Acquired Immune Deficiency Syndromes 03/2009; 50(3):290-3. · 4.43 Impact Factor
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Journal of the International Association of Physicians in AIDS Care (JIAPAC) 01/2009; 7(6):281-2.
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Jennifer R King, Edward P Acosta,
Ram Yogev,
Andrew Wiznia,
Joyce Kraimer,
Bobbie Graham,
Vincent Carey,
Paula Britto,
Patrick Jean-Philippe,
John Moye,
Douglas Watson
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ABSTRACT: The pharmacokinetics of lopinavir/ritonavir (LPV/RTV) 300 mg/m twice daily and efavirenz (EFV) 350 mg/m once daily were evaluated in HIV-infected children. The minimum concentrations for LPV contained values above the target range, and the estimated minimum concentrations for EFV contained values below the range. Our data support the current LPV/RTV dose, but EFV 350 mg/m may not be sufficient.
The Pediatric Infectious Disease Journal 01/2009; 28(2):159-61. · 3.58 Impact Factor
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ABSTRACT: Highly active antiretroviral therapy, which is widely available throughout developed countries, has become increasingly effective for treating the human immunodeficiency virus. In contrast, access to antiretroviral therapy in low-income countries is difficult at best. Thus, antiretroviral therapy for pediatric patients in resource-rich countries predominantly targets new drugs, and in low-income countries focuses on acquiring inexpensive, generic antiretroviral compounds available in pediatric-friendly formulations. Regardless of the economic region, success of antiretroviral therapy in pediatric patients depends upon our understanding of the physiological differences in drug absorption and disposition that occur with age, and our ability to adjust antiretroviral dosing according to these changes. The purpose of this review is to describe these differences and present recently published pharmacokinetic data of antiretrovirals in pediatric patients.
Antiretroviral pharmacokinetic data in pediatric patients are limited. Recent data, however, continue to illustrate that antiretroviral pharmacology differs in children and adolescents when compared with adults.
This review describes our current understanding of pharmacology in pediatric patients and summarizes key pharmacokinetic data on antiretroviral agents presented over the past year. We briefly describe how pediatric pharmacology impacts future research and drug development of antiretroviral agents.
Current opinion in HIV and AIDS 06/2008; 3(3):272-6. · 4.75 Impact Factor
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ABSTRACT: A highly sensitive and specific atmospheric pressure chemical ionization liquid chromatography-tandem mass spectrometry method was developed for serum pharmacokinetic studies of puerarin in rats. Chromatography was carried out on a reversed-phase Phenomenex Synergi 4 microm Fusion-RP80 column (150 x 2.0 mm i.d.) using a mobile phase consisting of acetonitrile-water (10:90, v/v) in 10 mm NH(4)OAc with a flow rate of 0.2 mL/min. Puerarin was analyzed in the multiple reaction monitoring mode with a precursor/product ion transition of m/z 415/267. The method was demonstrated to be specific and sensitive, and a linear response was observed over a range of 2-5000 ng/mL in rat serum. The validated method was successfully applied to the characterization of the pharmacokinetics of puerarin in rat serum after oral administration to spontaneously hypertensive rats. The blood concentration-time profile of puerarin showed a rapid initial increase, reaching a maximum and then declining within 1 h. Puerarin could not be detected after 24 h. The main pharmacokinetic parameters for puerarin after oral administration were as follows: C(max) (3.54 +/- 2.03 mg/L), T(max) (0.68 +/- 0.37 h), AUC(0-t) (7.29 +/- 3.79 mg h/L), AUC(0-infinity) (9.17 +/- 4.87 mg h/L), T(1/2) (1.7 +/- 0.6 h), CL/F (7.24 +/- 4.27 L/h/kg) and V/F (17.88 +/- 13.55 L/h/kg).
Biomedical Chromatography 05/2007; 21(4):410-4. · 1.97 Impact Factor
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The Lancet 09/2003; 362(9384):667. · 38.28 Impact Factor
