Subtypes of human immunodeficiency virus type 1 and disease stage among women in Nairobi, Kenya

In sub-Saharan Africa, where the effects of human immunodeficiency virus ty pe 1 (HIV-1) have been most devastating, there are multiple subtypes of thi s virus. The distribution of different subtypes within African populations is generally not linked to particular risk behaviors. Thus, Africa is an id eal setting in which to examine the diversity and mixing of viruses from di fferent subtypes on a population basis. In this setting, it is also possibl e to address whether infection with a particular subtype is associated with differences in disease stage. To address these questions, we analyzed the HIV-1 subtype, plasma viral loads, and CD4 lymphocyte levels in 320 women f rom Nairobi, Kenya. Subtype was determined by a combination of heteroduplex mobility assays and sequence analyses of envelope genes, using geographica lly diverse subtype reference sequences as well as envelope sequences of kn own subtype from Kenya. The distribution of subtypes in this population was as follows: subtype A, 225 (70.3%); subtype D, 65 (20.5%); subtype C, 22 ( 6.9%); and subtype G, 1 (0.3%). Intersubtype recombinant envelope genes wer e detected in 2.2% of the sequences analyzed. Given that the sequences anal yzed represented only a small fraction of the proviral genome, this suggest s that intersubtype recombinant viral genomes may be very common in Kenya a nd in other parts of Africa where there are multiple subtypes. The plasma v iral RNA levels were highest in women infected with subtype C virus, and wo men infected with subtype C virus had significantly lower CD4 lymphocyte le vels than women infected with the other subtypes. Together, these data sugg est that women in Kenya who are infected with subtype C viruses are at more advanced stages of immunosuppression than women infected with subtype A or D. There are at least two models to explain the data from this cross-secti onal study; one is that infection with subtype C is associated with a more rapid disease progression, and the second is that subtype C represents an o lder epidemic in Kenya. Discriminating between these possibilities in a lon gitudinal study will be important for increasing our understanding of the r ole of specific subtypes in the transmission and pathogenesis of HIV-1.