HIV-1 viral rebound dynamics after a single treatment interruption depends on time of initiation of highly active antiretroviral therapy

Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, and Center for Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
AIDS (London, England) (Impact Factor: 5.55). 09/2008; 22(13):1583-8. DOI: 10.1097/QAD.0b013e328305bd77
Source: PubMed


An important pending question is whether temporary highly active antiretroviral therapy during primary HIV infection can influence viral rebound dynamics and the subsequently established viral setpoint, through preservation and enhancement of HIV-1-specific immune responses, or through other mechanisms.
We included all patients from two prospective studies who underwent a single treatment interruption while being well suppressed on highly active antiretroviral therapy. One group started highly active antiretroviral therapy during primary HIV infection, and the other group started it during chronic HIV infection with CD4 cell counts above 350 cells/microl. Data were collected up to 48 weeks from treatment interruption. The median time to viral rebound was analysed for three levels of viraemia: 50, 500 and 5000 copies HIV-RNA/ml plasma.
The median time to viral rebound was significantly longer in primary HIV infection patients (n = 24) than in chronic HIV infection patients (n = 46): 8 versus 4 weeks (P < 0.001 for all three endpoints). In two primary HIV infection patients, no rebound of plasma HIV-1 RNA over 50 copies/ml occurred. In the first 4 weeks after treatment interruption, CD4+ T-cell counts declined with a median of -5.0 cells/microl blood per week in the primary HIV infection group and -45 cells/microl blood per week in the chronic HIV infection group (P < 0.05). From week 4 to 48, the decline in CD4+ T-cell count was similar in both groups.
Plasma viral load and CD4 dynamics after a single interruption of highly active antiretroviral therapy were different for primary HIV infection and chronic HIV infection patients. Viral rebound is delayed or absent and early CD4 cell count decline after treatment interruption is less pronounced in primary HIV infection patients.

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    • "Reservoirs levels in post-treatment controllers during the control phase were very low and it was mostly associated to the transitional memory CD4 þ T cell subset, due to a skewed distribution of quiescent CD4 þ T cell subsets in these patients (Saez-Cirion et al., 2013) (Fig. 2). Treatment interruption in patients who started cART during chronic phase leads to viral rebound within weeks, with viral loads frequently reaching pretreatment set-point levels (Fernandez Guerrero et al., 2005; Steingrover et al., 2008; Wit et al., 2005). Notwithstanding, some patients that started cART during chronic phase were also described to maintain controlled levels of viremia after therapy discontinuation (Van Gulck et al., 2011). "
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    • "Thus, thwarting HIV replication by introducing HAART in the early phases of infection could have a substantial impact on the whole disease course. In particular, suggested factors that may contribute to the observed better viral control after treatment interruption in very early treated patients are [3]: i) early arrest of viral escape, leaving the virus vulnerable; ii) preservation or even enhancement of the immune response resulting from the early clearing of antigen; iii) prevention of the establishment of a pool of HIV-specific memory CD4 T cells thus leaving fewer target cells available for viral infection. "
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    • "However, there are two major differences between the cohorts used in [6] and in the present article: a) in the former, patients have been recruited with a negative western blot for anti-HIV antibodies hence before seroconversion while in the latter, cohort data includes patients classified in stage IV, V and VI with respect to [9] (see Table 2); b) in [6] patients were treated with an intensive HAART consisting of two or three NRTIs plus a NNRTI and a PI, whereas our patients were treated with just two NRTI and one PI. These two features might be the cause of a lower level of viremia at the end of HAART accounting for a slower viral rebound in [6]. "
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