%0 Journal Article
%T beta-estradiol attenuates the anti-HIV-1 efficacy of Stavudine (D4T) in primary PBL
%A Mingjie Zhang
%A Qingsheng Huang
%A Yong Huang
%A Owen Wood
%A Weishi Yuan
%A Caren Chancey
%A Sylvester Daniel
%A Maria Rios
%A Indira Hewlett
%A Kathleen A Clouse
%A Andrew I Dayton
%J Retrovirology
%D 2008
%I BioMed Central
%R 10.1186/1742-4690-5-82
%X Human PBL were infected with HIV-1 in the presence or absence of combinations of sex steroid hormones and the anti-retroviral drug, D4T. After seven days in culture, viral supernatants were assayed for HIV-1 p24 protein. ¦Â-estradiol resulted in a modest inhibition of HIV-1 replication of ~26%. However, 2 nM ¦Â-estradiol increased the amount of HIV-1 replication in the presence of 50 nM D4T from a baseline of 33% (+/- SE = 5.4) to 74% (+/- SE = 5.4) of control virus levels in the absence of drug. Both results were statistically highly significant (p < 0.001). ¦Â-estradiol did not increase the replication of a D4T-resistant strain of HIV in the presence of D4T. The effects were unlikely to be due to general cell inhibition or toxicity because these concentrations of drug and hormone cause no cytotoxicity in PBL as measured by trypan blue exclusion.¦Â-estradiol inhibited both HIV-1 replication in primary human PBL and the antiretroviral efficacy of D4T in PBL cultures. To optimize antiretroviral drug therapy, it may be necessary to monitor patient hormonal status.Although there is evidence that viral load and anti-retroviral responses of women differ from those of men [1-3], little is known about gender-specific effects of HIV infection and treatments. Female hormones, including hormonal contraceptives, are known to play an important role in predisposition for many infectious diseases [4]. Whether sex steroid hormones influence susceptibility to HIV-1 infection, severity of symptoms, risk of disease progression or interference of anti-retroviral therapy is not clear. However, a recent epidemiology study reported that the HIV-1 viral load in blood is lower in women than in men at similar stages of HIV-1 infection, suggesting that there are gender effects in HIV/AIDS progression [5]. Furthermore, Lee et al reported that progesterone and Zidovudine (AZT) synergistically inhibited HIV-1 replication in primary placental macrophages, possibly explaining why AZT can inhibit mate
%U http://www.retrovirology.com/content/5/1/82