Greater Diversity of HIV-1 Quasispecies in HIV-Infected Individuals With Active Tuberculosis

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Abstract
Objective:A continual increase in intrapatient HIV-1 heterogeneity is thought to contribute to evasion of host immune response and eventual progression to AIDS. Tuberculosis (TB) is diagnosed both early and late during the course of HIV-1 disease and may increase diversity of HIV-1 quasispecies by activating the HIV-1 immune response and increasing HIV-1 replication. We examined whether HIV-1 heterogeneity is altered in HIV-1-infected individuals with TB. Methods:Blood samples were obtained from 7 HIV-1-infected patients with active TB (HIV/TB patients) and 9 HIV-1-infected patients (HIV patients) in Kampala, Uganda (CD4 counts of 0-650 cells/μl and HIV loads of 700-750,000 RNA copies/ ml). The C2-C3 region of the HIV-1 envelope gene (env) was amplified by nested polymerase chain reaction (PCR) from lysed peripheral blood mononuclear cells (PBMCs) of each patient, and then subject to sequencing, clonal-quasispecies analysis and heteroduplex tracking analysis (HTA). Results:HTA of env DNA fragments showed increased heterogeneity in the HIV/ TB individuals compared with the HIV group. Further sequence and HTA analysis on ten individual env clones for each patient showed significantly greater HIV mutation frequencies in HIV/TB patients than in HIV patients. Conclusion:An increase in HIV-1 heterogeneity may be associated with a TB-mediated increase in HIV-1 replication. However, a diverse HIV-1 quasispecies population in HIV/TB patients as opposed to tight quasispecies clusters in HIV patients suggests a possible dissemination of lung-derived HIV-1 isolates from the TB-affected organ. Address correspondence and reprint requests to Eric J. Arts, Division of Infectious Diseases, BRB 1034, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, U.S.A.; email: [email protected] Manuscript received March 31, 2000; accepted June 16, 2000. © 2000 Lippincott Williams & Wilkins, Inc.