Early and persistent bone marrow hematopoiesis defect in simian/human immunodeficiency virus-infected macaques despite efficient reduction of viremiaby highly active antiretroviral therapy during primary infection

The hematological abnormalities observed in human immunodeficiency virus (H IV)-infected patients appear to be mainly due to bone marrow dysfunction. A macaque models of AIDS could greatly facilitate an in vivo approach to the pathogenesis of such dysfunction. Here, we evaluated in this model the imp act of infection with a pathogenic simian/human immunodeficiency virus (SHI V) on bone marrow hematopoiesis. Three groups of macaques were inoculated w ith 50 50% median infective doses of pathogenic SHIV 89.P, which expresses env of dual-tropic HIV type 1 (HIV-1) 89.6 primary isolate. During the prim ary phase of infection, animals were treated with either a placebo or highl y active antiretroviral therapy (HAART) combining zidovudine, lamivudine, a nd indinavir, initiated 4 or 72 h postinfection (p.i.) and administered twi ce a day until day 28 p.i. In both placebo-treated and HAART-treated animal s, bone marrow colony-forming cells (CFC) progressively decreased quite ear ly, during the first month p.i. One year p.i., both placebo- and HAART-trea ted animals displayed decreases in CFC to about 56% of preinfection values. At the same time, a dramatic decrease (greater than 77%) of bone marrow CD 34(+) long-term culture-initiating cells was noted in all animals were foun d. No statistically significant differences between placebo- and HAART-trea ted monkeys were found. These data argue for an early and profound alterati on of myelopoiesis at the level of the most primitive CD34(+) progenitor ce lls during SHIV infection, independently of the level of viremia, circulati ng CD4(+) cell counts, or antiviral treatment.