Important note: Information in this article was accurate in May 1999. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; Monday, May 24, 1999
Daniel J. DeNoon, Senior Editor
Data showing that more than 20 percent of circulating HIV-1 strains in sub-Saharan Africa are intersubtype recombinants suggest that HIV recombinants are either favored for transmission or are formed much more commonly than expected.
Data showing that people infected with clade C HIV-1 have more advanced disease suggest either that clade C virus is more pathogenic, or that it has been around longer than other clades.
And data showing that women infected with clade C virus were more likely to shed virus in vaginal secretions - taken together with earlier findings of a low incidence of CXCR4 (X4) strains in the clade - suggest that clade-C-enveloped viruses may have replication capabilities different from other, better-studied HIV-1 clades.
"This can only be directly addressed by longitudinal studies of disease progression in relation to viral subtype, particularly in cohorts in which clade C virus infection represents a more significant fraction of all HIV-1 infections," wrote University of Washington researchers Joel R. Neilson, Julie Overbaugh, and colleagues.
"Certainly such information on differences in the biological properties or pathogenesis of different subtypes will be important in designing strategies to limit the spread of the most virulent HIV-1 variants."
Neilson et al. reported their findings in the Journal of Virology ("Subtypes of Human Immunodeficiency Virus Type 1 and Disease Stage among Women in Nairobi, Kenya," J Virol 1999 May;73(5):4393-403.
The researchers analyzed the envelope sequences of HIV-1 isolated from 320 women in Nairobi, Kenya, who were participating in a study of HIV transmission via breast feeding. They also collected data on plasma viral loads and CD4(+) T-cell counts.
HIV-1 subtype distribution was: subtype A, 70.3 percent (n=225); subtype D, 20.5 percent (n=65), subtype C, 6.9 percent (n=22); subtype G, 0.3 percent (n=1); and intersubtype recombinants, 2.2 percent (n=7).
Since only 10 percent of the viral genome was analyzed, the authors noted that even conservative estimates make the true frequency of intersubtype recombinants much higher.
"If we extrapolate ... then >20 percent of Kenyan HIV-1 proviral genomes would be predicted to be intersubtype recombinants," they wrote. "These estimates are likely to be relevant for most of sub- Saharan Africa because there are similar mixtures of multiple subtypes in many countries in this region."
Recombinant HIV subtypes arise when a single cell is infected with more than one HIV subtype. That dual infection can occur attests to the inability of natural HIV infection to protect against reinfection. But the determinants of dual HIV infection are poorly understood. Is reinfection very common, or are recombinant viruses more easily transmitted? If they are more easily transmitted, do they arise from true genetic recombinants or are they assembled from particles produced by different cells infected with different subtypes?
"It will be important to distinguish between these possibilities in considering the design of vaccines for African populations," Neilson et al. warned.
The authors urged the undertaking of longitudinal studies to answer the many intriguing questions posed by their findings.
This work was supported by grants from the National Institutes of Health (NIH), the National Institute of Child Health and Human Development, by a New Investigator Award from the University of Washington Center for AIDS Research, by an NIH Clinical Scientist Award, and by a cooperative agreement between the Henry M. Jackson Foundation for the Advancement of Military Medicine and the U.S. Department of Defense.
The corresponding author for this study is Julie Overbaugh, Program in Molecular Medicine, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, Washington 98195. Phone: (206) 667- 4418. Fax: (206) 667-6524. Email: <joverbau@fhcrc.org>.
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