Transplacental genotoxicity of combined antiretroviral nucleoside analogue therapy in Erythrocebus patas monkeys.

摘要: Summary: Antiretroviral nucleoside analogue drugs are a major constituent of highly active antiretroviral therapy (HAART). the most advanced form treatment for HIV-1 infection. Currently, HAART combinations that include zidovudine (ZDV) and lamivudine (3TC) effective in preventing vertical transmission; children born with no evident adverse clinical effects. However, ZDV is moderately strong transplacental carcinogen mice, potential long-term consequences fetal exposure to remain unknown. To model human 3TC exposures, experiments were performed Erythrocebus patas monkeys given human-equivalent drug protocols. Pregnant dosed either (n = 2), 40.0 mg ZDV/d (about 6 mg/kg body weight/d) last 50% (10 weeks) gestation 3), or same regimen plus 24.0 3TC/d 3.6 20% (4 3). Multiple organs examined at term DNA incorporation using two separate radioimmunoassays (RIAs). Values ZDV-DNA similar fetuses exposed alone those 3TC. 3TC-DNA greater than equal values ZDV-DNA, indicating total damage sustained by both was least double observed alone. Telomere shortening, determined Southern blot telomeric probe, three animals utero No telomere shortening unexposed fetuses, occasional found Overall, these studies demonstrate monkey combination sustain higher level drug-DNA show evidence more