CEREBROSPINAL-FLUID HIV-1 RNA AND DRUG CONCENTRATIONS AFTER TREATMENTWITH LAMIVUDINE PLUS ZIDOVUDINE OR STAVUDINE

Background Treatment and prevention of HIV-l-related central-nervous-s ystem disease may be dependent on penetration of antiretroviral drugs into the central nervous system. Few data are available about cerebros pinal-fluid penetration and concomitant changes of HIV-1-RNA concentra tions during treatment with antiretroviral agents. We investigated the se effects in HIV-1-infected people. Methods 28 antiretroviral-naive i ndividuals with CD4 cell counts of 200/mu L or more and plasma HIV-1-R NA concentrations of 10000 or more copies/mL who were free of neurolog ical symptoms were randomly assigned lamivudine plus either stavudine (n=17) or zidovudine (n=11). We did lumbar punctures on 28 individuals before and 22 individuals after 12 weeks of treatment to assess HIV-1 -RNA and drug concentrations in cerebrospinal fluid. Findings All 28 i ndividuals had detectable HIV-1-RNA concentrations in the cerebrospina l fluid (median 4.64 log(20) copies/mL and 4.20 log(10) copies/mL in t he lamivudine plus zidovudine and lamivudine plus stavudine groups, re spectively). There was no correlation between plasma and cerebrospinal -fluid HIV-1-RNA concentrations (r=0.18, p=0.35). After 12 weeks of tr eatment none of the individuals had detectable HIV-1-RNA concentration s in the cerebrospinal fluid. The highest drug concentration in the ce rebrospinal fluid was for lamivudine followed by stavudine and zidovud ine. Concentrations were consistent over time, unlike plasma concentra tions. Therefore, we found time-dependent cerebrospinal-fluid to plasm a drug-penetration ratios, which were highest for zidovudine followed by stavudine and lamivudine. Interpretation The two drug combinations were equally effective in the decrease of cerebrospinal fluid HIV-1-RN A concentrations. All drugs penetrated the cerebrospinal fluid. Antire troviral drugs other than zidovudine might be useful in the prevention of AIDS dementia complex.