AEGiS-14IAC: Relationship of genetic diversity and viral setpoint in HIV-1 crf02-a/g-ibng-infected women in Dakar, Senegal.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Relationship of genetic diversity and viral setpoint in HIV-1 crf02-a/g-ibng-infected women in Dakar, Senegal.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. A10033)

Mani I, Gilbert P, Sankale JL, Eisen G, Mboup S, Kanki PJ
Harvard School of Public Health, Boston, United States

We examined the intrapatient diversity and divergence in 12 HIV-1 CRF02-A/G-IbNG-infected seroincident women in Dakar, Senegal, determined whether a viral setpoint kinetic pattern existed for A/G_IbNG in the disease-free interval, and correlated viral load level and diversity. Samples were drawn from consenting A/G_IbNG infected, antiretroviral-naïve female commercial sex workers in Dakar, Senegal. Each individual had 2 or more plasma RNA values with a minimum of six months time interval. Mean values per individual of <4,000 copies/ml (low viral load group, n=5) or >30,000 copies/ml (high viral load group, n=7) were included. Two DNA samples from each person: earlier and later timepoint samples with at least six months time interval. Samples were drawn in the disease-free interval. 3 DNA PCRs of the env C2V3 performed, and 3-5 clones were sequenced from each PCR for both timepoints. Gag p24/p7 was sequenced for each person. Diversity and divergence was determined at each timepoint and over time using PHYLIP, ClustalX, Stata and Splus. Most individuals followed the viral setpoint paradigm. All women were IbNG in the env and the gag fragments. For each 1 log₁₀ copy/ml increase in viral load, intrapatient diversity increases by 1.4% (p=.028). Greater diversification rate was observed in the high group compared to the low group (p=.01), greater nucleotide (p=.015) and amino acid (p=.048) divergence and greater nucleotide divergence rate (p=.03) was found again in the high viral setpoint group. There was no difference in the dn/ds ratios between groups. Greater diversity, divergence and diversification rates seen in the high viral setpoints supports the notion that diversity is driven by the cycles of replication where diversity is generated by a fixed RT error rate, and resulting accumulated mutations. Recognizing diversity potential based on viral load levels early in epidemics may inform the design of vaccines and therapies in infected individuals.

020707
A10033