Chronic alcohol use affects therapeutic steady state plasma drug concentrations of stavudine, lamivudine and nevirapine in HIV-infected patients during 9 months follow up period: WHO AUDIT tool application G

Godfrey S. Bbosa, David B. Kyegombe, William W. Anokbonggo, Muhammad Ntale, David Musoke, John Odda, Aloysius Lubega, Jasper Ogwal-Okeng


Chronic alcohol consumption is a common problem among the HIV-infected patients on HAART. The study determined the effect of chronic alcohol use on steady state plasma drug concentrations of stavudine (d4T), lamivudine (3TC) and nevirapine (NVP) in HIV-infected patients during the 9 months follow up period. It also determined whether there were some patients with undetectable plasma drug concentrations in their plasma during the follow up. A case control using repeated measures design with serial measurements model, where plasma drug concentrations were measured at 3 month intervals was used. Chronic alcohol-use using WHO AUDIT tool was used to screen patients. A total of 41 patients (21 alcohol group and 20 control group) were followed up for 9 months with blood sampling done at 3 month intervals. The Shimadzu Class-VPTM HPLC Chromatography data system version 6.1 equipment with UV detector was used to measure the plasma drug concentrations. Data was analyzed using SAS 2003 version 9.1 statistical package with repeated measures fixed the model and means were compared using the student t-test. The mean steady state plasma concentration of both d4T and 3TC in chronic alcohol use group were lower than in the control group all throughout the 9 months period of follow-up. The mean steady state plasma drug concentrations of NVP were higher in the alcohol group at 0 and 3 months and lower in the 6 and 9 months as compared to the control group. The mean total plasma NVP concentration was higher in the chronic alcohol group as compared to the control group and the difference was statistically significant (p≤0.05). However some patients had undetectable plasma drug concentrations despite of having ≥ 95 % adherence rate. Chronic alcohol use by the HIV-infected patients lowers the steady state plasma drug concentrations of d4T, 3TC and NVP in patients.


Chronic alcohol use, Therapeutic steady state plasma drug concentrations, HIV, d4T, 3TC, NVP

Full Text:



GENACIS, Alcohol, Gender and Drinking Problems:Perspectives from Low and Middle Income Countries. Geneva, Switzerland. World Health Organization 2005. p. 2-241.

WHO, Global Status Report on Alcohol 2004. 2004: Geneva, Switzerland.

WHO, Alcohol and Injury in Emergency Department: Summary of the Report from the WHO Collaborative Study on Alcohol and Injuries. WHO Library Cataloguing-in-Publication Data, 2007: p. 1-11.

Micheal G. Alcohol health issues related to alcohol consumption. The place of alcohol in human culture, 1996: p. 1-22.

Kafuko, A. and P. Bukuluki, Qualitative research in Uganda on knowledge, attitude and practices concerning alcohol. 2008, USAID, Health Communication, YEAH and Afford: Corporate Agreement number 617-A-00-07-00005-00.

Lwanga-Ntale, C., Drinking into deeper poverty: The new frontier for Chronic Poverty in Uganda. Chronic Poverty Research Center: Development Research and Training. Policy Brief No.1/2007., 2007.

YEAH, Alcohol Consumption in Uganda: Literature Review. (Young Empowered and Health -YEAH) (Accessed on 22/07/09). 2007.

Zakhari, S., Overview: How is alcohol metabolised by the body? The Journal of the National Institute on Alcohol Abuse and Alcoholism., 2006. 29(4): p. 245-252.

Edenberg, H.J., The role of alcohol dehydrogenase and aldehyde dehydrogenase variants:The genetics of alcohol metabolism. The Journal of the National Institute on Alcohol Abuse and Alcoholism., 2007. 30(1): p. 5-12.

Fleming, M., S.J. Mihic, and R.A. Harris, Ethanol. Goodman Gilman’s, the pharmacological basis of therapeutics. McGraw-Hill Medical publishing Division, New York. 10th ed. 2001(18): p. 429-442.

Moore, S., et al., Variations in alcohol-metabolizing enzymes in people of East India and African descent from Trinidad and Tobago. The Journal of the National Institute on Alcohol Abuse and Alcoholism., 2007. 30(1): p. 28-30.

Quertemont, E. and V. Didone, Role of acetaldyde in mediating the Pharmacological and Behavioral effects of alcohol. The Journal of the National Institute on Alcohol Abuse and Alcoholism., 2006. 29(4): p. 258-264.

Gore, K.A., R.J. Harris, and J.M. Firestone, Differences in male and female alcohol consumption. American Sociological Association Annual Meetings, August 14-17, San Francisco, CA 2008. USA. Allacademic Research journal, 2008: p. 1-20.

Orrick, J.J., Antiretroviral drug interactions. Infectious Diseases: HIV/AIDS Primary care guide, Florida Aids Education and Training Centre, University of Florida. , 2002. 7: p. 69-81.

Scott, D.M. and R.E. Taylor, Health-related effects of genetic variations of alcohol-metabolising enzymes in African Americans. The Journal of the National Institute on Alcohol Abuse and Alcoholism., 2007. 30(1): p. 18-20.

Hoetelmans, R.M.W., Clinical Pharmacokinetics of Antiretroviral Drugs. AIDS Reviews., 1999. 1: p. 167-178.

L’hommea, R.l.F.A., et al., Nevirapine, stavudine and lamivudine pharmacokinetics in African children on paediatric fixed-dose combination tablets. AIDS. 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins., 2008. 22: p. 557-565.

FDA, AIDSinfo Drug Database: Offering on HIV/AIDS Treatment, Prevention and Research. AIDSinfo, 2013: p. (Cited on July 2013).

Tremoulet, A.H., et al., Population Pharmacokinetics of Lamivudine in Human Immunodeficiency Virus-Exposed and -Infected Infants. Antimicrobial agents and Chemotherapy. December. 2007. , 2007. 51(12): p. 4297-4302.

Belle, D.J. and H. Singh, Genetic Factors in Drug Metabolism. American Family Physician, 2008. 77(11): p. 1553-1560.

Krishna, D.R. and M.S. Shekar, Cytochrome P450 3A: Genetic polymorphisms and interethnic differences. Methods and Findings in Experimental Clinical Pharmacology, 2005. 27(8): p. 559.

Penzak, S.R., et al., Cytochrome P450 2B6 (CYP2B6) G516T influences nevirapine plasma concentrations in HIV-infected patients in Uganda. HIV Medicine 2007: British HIV Association., 2007. 8: p. 86-91.

Bartlett, J.G. and J.E. Gallant, Medical Management of HIV Infection. Johns Hopkins University School of Medicine. Johns Hopkins Medicine Health Publishing Business Group. Baltimore, USA.2005-2006. , 2006.

Chuang, J.C. and P.A. Jones, Epigenetics and MicroRNAs. Pediatric Research, 2007. 61(5): p. 24R-29R. DOI: 10.1203/pdr.0b013e3180457684.

Lim, S.O., et al., Epigenetic changes induced by reactive oxygen species in hepatocellular carcinoma: methylation of the E-cadherin promoter Gastroenterology, 2008. 135: p. 2128-2140.

Mathers, J.C., G. Strathdee, and C.L. Relton, Induction of epigenetic alterations by dietary and other environmental factors. Advances in Genetics, 2010. 71: p. 3-39.

Starkman, B.G., A.J. Sakharker, and S.C. Pandey, Epigenetics - Beyond the Genome in Alcoholism. Alcohol Research: Current Reviews. The Journal of the National Institute on Alcohol Abuse and Alcoholism, 2012. 34(3): p. 293-304.

Singh, S. and S. Li, Epigenetic Effects of Environmental Chemicals Bisphenol A and Phthalates. International Journal of Molecular Sciences, 2012. 13: p. 10143-10153; doi:10.3390/ijms130810143.

Evans, W.E. and H.L. McLeod, Pharmacogenomics - Drug Disposition, Drug Targets, and Side Effects. The New England Journal of Medicine, 2003. 348(6): p. 538-549.

Flaherty, D.K., Single Nucleotide Polymorphisms, Drug Metabolism and Untoward Health Effects. Journal of Medical and Biological Sciences, 2007. 1(2): p. 1-8.

Srivastava, P., Drug Metabolism and Individualized Medicine. Current Drug Metabolism, 2003. 4: p. 33-44.

Epstein, M., Alcohol’s Impact on Kidney Function. Alcohol Health and Research World, 1997. 21(1): p. 84-93.

Heringlake, M., et al., The effects of ethanol and vasopressin on renal function in the isolated perfused rat kidney. Applied Cardiopulmonary Pathophysiology, 2011. 15: p. 24-28.

Vella, D.L. and D. Cameron-Smith, Alcohol, Athletic Performance and Recovery. Nutrients, 2010. 2: p. 781-789; doi:10.3390/nu2080781.

Brunton, L.L., J.S. Lazo, and K.L. Parker, Antiretroviral agents and treatment of HIV infection. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th edition. 2006: p. 1273-1309.

Ferreira, M.P. and D. Willoughby, Alcohol Consumption: the good, the bad and the indifferent. Journal of Applied Physiology, Nutrition and Metabolism., 2007. 33: p. 12-20.

Triplit, C., Drug Interactions of Medications Commonly Used in Diabetes. Diabetes Spectrum, 2006. 19(4): p. 202-211.

Babor, T.F., et al., The Alcohol Use Disorders Identification Test (AUDIT) Manual: Guidelines for Use in Primary Care. Second Edition. Department of Mental Health and Substance Dependence. World Health Organization 2001. WHO/MSD/MSB/01.6a., 2001: p. 4-32.

Notari, S., et al., Simultaneous determination of 16 anti-HIV drugs in human plasma by high-performance liquid chromatography. Journal of Chromatography B, 2006. 831: p. 258-266.

Gautam, C.S., A. Utreja, and G.L. Singal, Singal, Spurious and counterfeit drugs: a growing industry in the developing world Postgraduate Medical Journal, 2009. 86: p. 251-256.

IMPACT, Counterfeit drugs kill. International Medical Products Anti-Counterfeiting Taskforce (IMPACT). World Health Organisation Drug Information, 2006.

Aberg, J.A., Perspective of Drug-Drug Interactions With Newer Antiretroviral Agents: Topics in HIV Medicine. International AIDS Society–USA., 2008. 16(5): p. 146-149.

Weathermon, R. and D.W. Crabb, Alcohol and medication interactions. Alcohol Research and Health, 1999. 23(1): p. 40-54.

Gomez, A. and M. Ingelman-Sundberg, Pharmacoepigenetics: Its Role in Interindividual Differences in Drug Response. Discovery. Nature Publishing Group, 2009. 84(4): p. 426-430.

Kirk, H., et al., Botanicals as epigenetic modulators for mechanisms contributing to development of metabolic syndrome. Metabolism Clinical and Experimental 2008. 57(Suppl 1): p. S16–S23.

Grandjean, A.C., Water requirements, impinging factors, and recommended intakes. The Center for Human Nutrition, University of Nebraska, Omaha, Nebraska, USA, 2012. 3: p. 25-40. 2012.

Bristol-Myers-Squibb, Stavudine (Zerit): Patient Information Leaflet. Bristol-Myers Squibb. New Jersay, USA., 2009.

Sabo, J.P., et al., Pharmacokinetics of Nevirapine and Lamivudine in Patients with HIV-1 Infection. AAPS PharmSci ( 2002. 2(1): p. 1-8.

Boehringer-Ingelheim, Nevirapine tablets. Boehringer Ingelheim Pharmaceuticals, Inc. CT, USA, 2008: p. 5-7.