HIV population shifts following HAART

Highly active antiretroviral therapy (HAART) involves combinations of protease inhibitors and other drugs to block HIV proliferation. While there is abundant evidence that this approach reduces viremia, far less is known about its qualitative effects on the surviving HIV population. HIV variants, sometimes called quasispecies, can differ in their host cell tropism, their pathological effects, and the structure of their envelope glycoprotein, env. Variation in env sequence causes determines which of two chemokine receptors, CXCR4 or CCR5, will be required as a coreceptor for viral entry. Typically, CCR5-dependent viruses (R5) are the major population early in the course of an infection, and CXCR4-dependent viruses (X4) overtake them later, leading to a drop in CD4+ T cell count. By following the relative prevalence of R5 and X4 viruses in a set of women with advanced disease, Philpott now show that R5 viruses can re-emerge as the predominant HIV-1 population following HAART or other combination therapies. Indeed, most of these subjects, even those with little reduction in their overall circulating HIV levels, showed a suppression of X4 strains in preference to R5 strains. The authors suggest that this qualitative effect could provide an additional basis for the benefit of combination therapies, independent of their quantitative effect on viral titer.