AEGiS-11IAC: HIV-1 subtype specific differences in plasma RNA levels related to rate and amount of virus produced in PBMC culture.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

HIV-1 subtype specific differences in plasma RNA levels related to rate and amount of virus produced in PBMC culture.

Int Conf AIDS 1996 Jul 7-12; 11:219 (abstract no. Tu.A.155)
De Wolf F, Von Briesen H, Holmes H, Bakker M, Cornelissen C, Goudsmit J; Department of Human Retrovirology, Academic Mecical Center, University of Amsterdam, Amsterdam, the Netherlands. Fax: 31-20-6916531.

OBJECTIVE: To investigate whether differences in replication could be found between HIV-1 subtypes by comparing the efficiency of PBMC culture, as well as HIV-1 genomic RNA levels measured in plasma of individuals newly infected with HIV-1 subtype B, E, A or D. Materials and

METHODS: HIV-1 RNA levels were measured by NASBA in the supernatant of standardized PBMC cultures, as well as directly in plasma of 55 individuals infected with HIV-1 subtype B (n=15), A (12), D (13) or E (15) sampled at a time point within 2 years of HIV-1 antibody seroconversion.

RESULTS: Differences in time to seroconversion and stage of HIV-1 infection as assessed by measuring beta2-microglobulin levels in plasma, did not have an impact on the results and neither did the number of mismatches of the strains in the primer/probe regions used in the NASBA. Infectivity of these subtypes (TCID50) was proportional to the HIV-1 RNA levels in the virus cultures. Monitoring PBMC cultures for p24 positivity revealed that subtype B became positive after 4 and A after 8 days of culture. Subtype D (12 days) and E (14 days) cultures took significantly (p=0.0001 and 0.0001) longer. HIV-1 RNA concentrations in the cultures of subtype E were lower and rose at a slower rate than in the cultures infected with the three other subtypes. HIV-1 RNA copy numbers directly measured in plasma were significantly lower in subtype E infected individuals compared to individuals infected by subtypes A (p=0.003), B (p=0.01) and D (p=0.003).

DISCUSSION: The HIV-1 RNA steady state level established during the first years of infection with HIV-1 subtype B predicts clinical outcome. HIV-1 RNA levels in plasma/serum are also predictive of the success rate of HIV-1 isolation from PBMC, indicating a link between replicative capacity of isolates in vitro and in vivo levels of HIV-1 RNA. Our results suggest that subtype-specific differences in HIV-1 RNA levels in vivo occur and are related to the rate and amount of virus produced from peripheral blood cells of newly infected individuals.

Keywords: AEGIS, HIV-1, HIV Infections, RNA, Viral, RNA, Virus Replication, Culture, In Vitro, ethnology, virology, ICA11

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