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Gender differences in HIV-1 diversity at time of infection

Abstract

To develop an HIV-1 vaccine with global efficacy, it is important to identify and characterize the viruses that are transmitted, particularly to individuals living in areas of high incidence. Several studies have shown that virus from the blood of acutely infected adults was homogeneous, even when the virus population in the index case was genetically diverse1,2,3,4. In contrast to those results with mainly male cohorts in America and Europe, in several cases a heterogeneous virus population has been found early in infection in women in Africa5,6. Thus, we more closely compared the diversity of transmitted HIV-1 in men and women who became infected through heterosexual contact. We found that women from Kenya were often infected by multiple virus variants, whereas men from Kenya were not. Moreover, a heterogeneous virus was present in the women before their seroconversion, and in each woman it was derived from a single index case, indicating that diversity was most likely to be the result of transmission of multiple variants. Our data indicate that there are important differences in the transmitted virus populations in women and men, even when cohorts from the same geographic region who are infected with the same subtypes of HIV-1 are compared.

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Figure 1: Comparison of the predicted amino-acid sequence of the envelope gene of proviruses from PBMCs of five men recently infected with HIV-1.
Figure 2: Phylogram of representative V1–V3 envelope gene sequences from women and men in this cohort.
Figure 3: Heteroduplex mobility assays of a 1.2-kb envelope fragment amplified from plasma samples obtained before seroconversion (PRE) and PBMCs obtained just after documented seroconversion (POST) from six women.

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Acknowledgements

We thank D. D. Panteleeff, M. Poss, R. Anderson, J. Neilson, J. Gosink and B. Chohan for technical assistance; B. Richardson for assistance with statistical analysis and discussions; J. Carr for advice on computational analyses; and J. Bwayo, J. Ndinya-Achola and the Nairobi HIV/STD Research Project for the continued collaborations and interactions that make this research possible. We also thank C. Giachetti, S. Bodrug and M. Bott of Gen-Probe for assistance with the HIV-1 RNA assay. This work was supported by the National Institutes of Health through grants AI38518 and AI33873 and through Family Health International subcontract N01-AI35173-119. E.M.L. was supported in part by National Institutes of Health predoctoral fellowship T32 GM07270.

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Correspondence to Julie Overbaugh.

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Michelle Long, E., Martin, H., Kreiss, J. et al. Gender differences in HIV-1 diversity at time of infection. Nat Med 6, 71–75 (2000). https://doi.org/10.1038/71563

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