Initiation of ART during recent HIV-1 Infection results in lower residual viral reservoirs and weak HIV-1 T cell specific responses

Antonio Pires¹, Gareth Hardy, Simon Portsmouth², Brian Gazzard², Frances Gotch¹ and Nesrina Imami¹. Dept Immunology at Imperial College¹, and Dept of GUM², Chelsea and Westminster Hospital, Fulham Road, London (UK)

Background: Initiation of antiretroviral therapy (ART) during primary HIV-1 infection has been shown to beneficially maintain virus specific T cell responses.  Although these effects may not be evident if ART is commenced during recent infection (>180 days after viral exposure) little is known regarding the effects of ART in residual viral reservoirs at different stages of infection. Material and Methods: From 40 HIV-1 infected subjects recruited for this study, 15 presented with recent infection (RI) (viral exposure >180 days but less than 1 year), 10 with chronic infection (CI) (>1 year) and 15 long term non-progressors (LTNP) (infected >5 years, therapy naïve and controlled viremia). Residual cellular proviral (p) DNA was assessed using the highly sensitive Amplicor MONITOR test (Roche Diagnostics, NJ). Virus specific responses were evaluated using intracellular cytokine staining and ³H-thymidine incorporation assays. Results: At baseline, HIV-1-pDNA median levels were 297.4 (IQR 165-618) and 248 (IQR 144-470) HIV-1 copies/mg total DNA in RI and CI respectively. Eight months post ART there was a significant decrease in pDNA in the RI group to 33 (IQR 21.4-104.7) HIV-1 copies/mg total DNA (p<0.05), which was comparable to the pDNA levels seen in the LTNP 16 (IQR 7.4-99) HIV-1 copies/mg total DNA. The same duration of ART in the CI group did not reduce the HIV-1 pDNA reservoir which remained higher [152 (IQR 76-157)] than those seen in RI and LTNP (p<0.02 for both). HIV-1-specific T cell responses were absent in >85% of RI patients at baseline, however 8 months post initiation of ART, HIV-1-specific T cell responses mainly directed at HIV-1-nef were detected in >40% of individuals. Intracellular cytokine staining revealed a similar pattern in which HIV-1-specific responses were transient throughout therapy but remained invariably low. CI showed an even lower frequency and magnitude of HIV-1-specific T cell responses. In contrast, LTNP showed vigorous HIV-1-specific responses. Conclusions: Initiation of ART during the early stages of disease appears to significantly reduce HIV-1 cellular reservoirs to levels comparable to those seen in LNTP. This is not apparent if therapy is started during chronic stages of infection. The timing appears to be more sensitive for preserving HIV-1-specific T cell responses as these do not appear to be significantly enhanced if ART is commenced post seroconversion even if during recent infection.