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: 4.56). 03/2008; 47(2):140-47. DOI: 10.1097/QAI.0b013e31815dbf7f
Source: PubMed


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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    Frontiers in Immunology 04/2013; 4:95. DOI:10.3389/fimmu.2013.00095
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    • "Although cART has been successful, it has not eradicated the disease as the virus can persist in resting memory CD4+ T cells as well as macrophages and astrocytes (Coiras et al. 2009). These latent reservoirs of HIV are easily and quickly activated if cessation of cART treatment occurs (Lewin et al. 2008). Elimination of these reservoirs is a major goal of current research in the HIV field. "
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    • "Production of HIV was quantified by measuring the Reverse Transcriptase activity in cell culture supernatant at days 4, 7, and 10 post-infection as previously described [48] as well as by measuring integrated HIV DNA and RNA at day 4 post-infection using real-time PCR (iCycler, Bio-Rad, Hercules, CA). Integrated HIV DNA was quantified using a nested Alu-long terminal repeat (LTR) PCR as previously described [49,50]. In brief, we used standards that contained random integration sites as previously described [51]; all samples were run in triplicate and we used an additional control reaction that included the LTR primer alone [49,50]. "
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