A Tale of Two Epidemics
In Thailand, India and sub-Saharan Africa, 90% of the cases of HIV-1 infection are believed to have resulted from heterosexual exposure, while in the U.S. and Europe less than 10% of HIV infections have been attributed to heterosexual contact. Nine different subtypes ("clades") of HIV-1 have been identified, and where B is the dominant subtype in the U.S., Western Europe, the Caribbean and Latin America; C is the dominant subtype in India; E, the dominant sub-type in Thailand; and A, C and D, the dominant sub-types in Africa. While differences in the rates of HIV-1 heterosexual transmission have been attributed to differing sexual behavior practices and co-factors, none of these explanations fully accounts for the explosive heterosexual epidemics in Africa and Asia. Now, investigators publishing their work in a recent issue ofScience (vol. 271: 1291-3) report that differences in HIV's affinity for certain epithelial cells which line the mouth and genital--but not the rectal--mucosa among these HIV-1 subtypes may explain the differences between the epidemiology of these epidemics. Furthermore, the authors warn that "If introduced into the West, viruses such as HIV-1 E might pose a greater threat for heterosexual transmission than does HIV-1 B."
In The Journal of Infectious Diseases (1996; 173: 355-64) in vitro additivity or synergy with the antiretroviral combinations 3TC+ddI, 3TC+d4T, 3TC+NVP, d4T+ddI, d4T+NVP, 3TC+SQV, d4T+SQV (among others) when tested against AZT-sensitive isolates of HIV. Curiously though, when these same combinations were tested against HIV isolates which had developed reduced sensitivity to AZT, the combination of AZT+d4T, in particular, appeared antagonistic. This antagonism is thought to be caused by AZT's ability to inhibit the phosphorylation of d4T. Both drugs also compete for the same cellular thymidine kinase, and AZT is preferentially phosphorylated over d4T.
This article was provided by Treatment Action Group. It is a part of the publication TAGline.