Lewin SR, Murray JM, Solomon A, et al. Virologic determinants of success after structured treatment interruptions of antiretrovirals in acute HIV-1 infection

Infectious Diseases Unit, Alfred Hospital, Melbourne, Australia.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.39). 03/2008; 47(2):140-47. DOI: 10.1097/QAI.0b013e31815dbf7f
Source: PubMed

ABSTRACT Latently infected resting memory CD4 T cells are thought to be the major reservoir that contributes to rebound viremia after cessation of antiretrovirals (ARVs). Commencing ARVs during primary HIV-1 infection (PHI) may limit the size of the latent pool and lead to improved control of viral replication during structured treatment interruption (STI).
Individuals with PHI (n = 59) were randomized to receive ARVs with or without hydroxyurea. After STI, a good response was defined as maintenance of HIV-1 RNA <5000 copies/mL for 24 weeks off therapy. In a detailed prospective virologic substudy (n = 19), integrated HIV-1 DNA, total HIV-1 DNA, and cell-associated HIV-1 unspliced (US) RNA were quantified using a real-time polymerase chain reaction assay.
The plasma HIV-1 RNA 12 weeks after the initiation of ARVs was significantly lower in good responders (n = 7) compared with poor responders (n = 12) (P = 0.005). There were no significant differences between good and poor responders in integrated HIV-1 DNA, HIV-1 DNA, and HIV-1 US RNA. Integrated HIV-1 DNA before initiation of ARVs was strongly correlated with plasma HIV-1 RNA at week 12 (P = 0.006, r = 0.81).
HIV-1 RNA measured 12 weeks after initiation of ARV was the only virologic variable associated with viral rebound after treatment interruption in PHI.

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    • "However, in another prospective study of PHI, eight EC were identified amongst 211 untreated PHI subjects (out of a total of 964 subjects enrolled), and there was no significant difference in symptomatic PHI (Goujard et al., 2009), but there was a clearly significant difference in HIV RNA viral load. Similarly, we found that patients who exhibited better control of HIV RNA, during treatment interruption after 6–12 months cART commenced during PHI, had a significantly lower HIV RNA level at baseline, by multivariate analysis (Bloch et al., 2006), and this correlated with lower levels of integrated HIV DNA prior to cART (Lewin et al., 2008). Another large natural history study showed that viral control was established in the majority of EC within 1 year of seroconversion , but characteristics of PHI were not reported for this cohort (Okulicz et al., 2009). "
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