Because semen is a major vehicle for the sexual transmission of HIV-1, control of viral replication within the sanctuary of the male genital tract should be a goal of antiretroviral therapy. Local immune responses, virus specific factors, and the degree of viral and cellular traYcking all appear to be important in controlling viral replication and evolution. However, the most important factor influencing viral replication and evolution within the male genital tract may be the disposition of antiretroviral agents into genital tissues and fluids. This review proposes possible mechanisms of antiretroviral distribution into the male genital tract by using other sanctuary barriers; such as the placenta, renal tubules, and blood-brain barrier; as models. In addition, this review summarises recent clinical studies regarding the disposition of currently available antiretroviral drugs into the seminal plasma and discusses some of the diYculties in interpreting drug concentration in the genital tract. (Sex Transm Inf 2001;77:4-11)
Human immunodeficiency virus (HIV) can be transmitted in semen from a man to his sexual partners. Antiretroviral drugs are likely to affect the amount of HIV-1 in semen and perhaps transmission of the virus. The concentrations of zidovudine, lamivudine, and HIV-1 RNA in blood and seminal plasma were measured in 9 HIV-positive men over =2 years. Median (25th-75th percentiles) zidovudine blood and seminal plasma concentrations were 64.2 (range, 48.4-206.9; n=82) and 292.5 (range, 194.3-438.4; n=79) ng/mL, respectively. Median lamivudine blood and seminal plasma concentrations were 391.3 (range, 175.3-793.8; n=82) and 2701.8 (range, 1460.5-4320.2; n=79) ng/mL, respectively. The concentration of HIV-1 RNA in seminal plasma was monitored as a potential surrogate marker for infectiousness. RNA became undetectable (<400 copies/mL) in the blood and seminal plasma of 8/9 subjects after initiation of therapy and remained undetectable in 6/9 subjects. These data show that zidovudine and lamivudine achieve high concentrations in seminal plasma and significantly reduce HIV-1 RNA. The effects of antiviral therapy on HIV-1 in semen and on the sexual transmission of HIV-1 require further study.
Data from the Brazilian Agricultural Ministry show that before the implementation of the Brazilian programme of nitrofuran control in February 2003, the cases of contamination of Brazilian chicken by nitrofurans were almost exclusively due to furaltadone. After May 2003, such cases decreased until no more reports of Brazilian chicken contamination with this nitrofuran were reported. Curiously, after April 2003, an increase was observed in the numbers of contaminated samples by semicarbazide, the target metabolite of nitrofurazone. Most Brazilian chicken found to be contaminated with semicarbazide has been covered with flour, salt and spices. For this reason, the authors' laboratory initialized a programme for tracing possible sources of food contamination by semicarbazide. After several semicarbazide positives in flour of controlled origin (results varying between 2.2 and 5.2 microg kg(-1)), the different additives used in the cereal industry as flour improvement agents were studied. The results indicate that the compound azodicarbonamide was responsible for the source of the contaminant semicarbazide.
The AIDS Clinical Trials Group Study 850 (ACTG 850) evaluated the penetration of zidovudine (ZDV), lamivudine (3TC), and amprenavir (APV), given alone and in combination with the 2 nucleoside analogues, into the male genital tract, because these factors may affect human immunodeficiency virus (HIV) type 1 suppression and transmission. Nineteen men receiving APV monotherapy and 12 men receiving triple therapy donated blood plasma (BP) and seminal plasma (SP) during therapy. Paired SP and BP were used to calculate compartmental concentration ratios. APV SP concentrations were consistently lower than BP concentrations, ZDV SP concentrations approximated BP concentrations early but became greater later in the dosing interval, and 3TC SP concentrations were substantially greater than BP concentrations throughout. Observed SP concentrations plotted with population BP concentration-time curves confirmed these findings, suggesting that passive diffusion (APV), slowed elimination (ZDV), and either active accumulation and/or inhibition of elimination (3TC) are responsible for SP concentrations of these agents. The antiretroviral effect of APV monotherapy was related to APV concentrations.
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