Increased vaginal shedding of HIV in pregnant women infected with subtype C

Pregnant women infected with subtype C of HIV-1 shed more of the virus in their vaginal mucosa, than women infected with subtypes A or D, according to a study conducted in Kenya and published in the August 1^st edition of the Journal of Infectious Diseases. However, the investigators found that the rate of mother-to-baby transmission of HIV was comparable between women infected with subtypes A, C and D.

Subtype C has been associated with the highest prevalence of HIV-1. However, it has been difficult to establish if the more rapid spread of subtype C is due to characteristics of the subtype or cofactors existing in the populations affected by this subtype.

It has been difficult to determine the role of subtype in HIV transmission as many regions have a dominance of one HIV-1 subtype. However, cohort studies in sub-Saharan Africa, examining mother-to-baby transmission of HIV, often include women infected with a variety of HIV subtypes. Mucosal shedding of HIV is frequently used as a surrogate marker of infectivity. Identifying differences in the shedding of different HIV subtypes can contribute to the understanding of the role played by subtype in HIV transmission.

Therefore, investigators compared cervical, vaginal and breastmilk shedding of HIV in a cohort of 365 women infected with HIV-1 subtypes A, C and D in Kenya. The women were enrolled to the study between 1992 and 1998. Swabs were obtained to measure cervical and vaginal secretions of HIV during the 32^nd week of pregnancy and samples of breastmilk were obtained during the second, sixth and tenth weeks after delivery. Blood samples were also taken.

The majority of women (71%) were infected with subtype A, 7% (25 individuals) were infected with subtype C, 20% were infected with subtype D and 2% were infected with recombinant subtypes.

Median age of the women was 23 years and median CD4 cell count before delivery was 422 cells/mm³. Women infected with subtype C, however, were older and had a lower CD4 cell count. Median plasma viral load was 39,800 copies/ml and this did not differ significantly by subtype.

Investigators found a significant correlation between plasma viral load and cervical (p

HIV shedding in breastmilk was significantly lower in women infected with subtype D (p = 0.04).

Among women with infants whose HIV status was known, 28% of women with subtype C transmitted HIV compared to 24% of women with subtype A and 21% of women with subtype D and the investigators note "transmission risk did not differ significantly between the subtypes."

Commenting on their findings the investigators write "to the extent that genital shedding of HIV-1 influences transmission, we would predict that transmission to infants or partners from women infected with subtype C would be more frequent than that from women infected with subtype A, and we would predict that subtype D would be least transmissible."

The investigators note that HIV is rapidly spreading in some areas of Africa where subtype C is predominant. However, they add that they have not observed an increase in the prevalence of subtype C in Kenya. They therefore speculate that cofactors such as partner networks, host factors, and concomitant sexually transmitted diseases in regions with subtype C epidemics may act synergistically with increased genital shedding to fuel rapid sexual spread of HIV."

Investigators acknowledged several limitations with the study, the biggest being the lack of statistical power to assess the role of subtype C on mother-to-baby transmission. Nevertheless, the investigators conclude, "we found significant differences in mucosal shedding of HIV-1 between subtypes…it seems unlikely that this alone accounts for the rapid spread of particular subtypes, such as subtype C, in certain parts of the world."