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141 Immune Correlates of HIV-1 Disease Progression in Subtype E-Infected Thais
T. Chuenchitra*1, C. Wasi2, S. Louisirirotchanakul2, M. de Souza1, S. Nitayaphan1, R. Sutthent2, A. Brown1, D. Birx3, and V. Polonis3
1AFRIMS, Bangkok, Thailand; 2Siriraj Hosp. Bangkok, Thailand; and 3US Military HIV Res. Program, Rockville, MD, USA
Background: Identification of immune correlates associated with slower disease progression may aid in vaccine design for geographic regions such as Thailand, where the prevalent subtypes (B and E) are well defined. The goals of this study were to measure viral load, neutralizing antibody (NAb), and binding antibody (Ab) in Thai patients with different rates of progression and to investigate correlation between these parameters and HIV-1 disease progression in subtype E-infected Thais.
Methods: Twenty subjects enrolled in a natural history protocol in Bangkok were studied. Nine progressors (PR; patients with CD4+ cells < 200/mm3 and progression to AIDS or death at the end of follow-up) and 11 slower progressors ( SP; patients who were asymptomatic or had CD4+ cell > 350/mm3 at the end of follow-up) were followed at least 36 months. NAb to B and E viruses and Ab titers to Gag and Env (by ELISA) were measured at study entry and at the end of follow-up. CD4+ counts and viral loads were measured at study entry and at the end of follow-up. CD4+ counts and viral loads were measured throughout the study.
Results: At study entry, the median viral load was significantly higher in PR than SP (p < 0.005), whereas CD4+ counts and Ab titers to Gag and Env were similar. At the end of follow-up, p24 Ab titers in PR showed a significant decrease (p < 0.001) but remained stable in SP. Titers of V3 and gp41 Ab did not significantly in either group. In SP (but not PR), increased NAb over time was observed against the subtype E primary isolate, TH023 (p = 0.004), and lab strain, NPO3 (p = 0.004). Both CD4bs and gp120 Abs correlated positively with NAb against NPO3 and TH023. However, V3 Ab correlated only with NAb against the NPO3 lab strain (r = 0.576; p < 0.001). Within the cohort, CD4+ count was inversely correlated with viral load (r = (0.314; p = 0.004) and positively correlated with p24 Ab (p = 0.022).
Conclusions: HIV-1 subtype E-infected slower progressors appear to retain the immune competence to develop new antibody responses over time; this may contribute to control of virus by the host. As described for subtype B, a decline in p24 Ab and increase in gp120 and CD4bs Abs may be predictive markers of disease progression.
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