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Background: The occurrence of viral control after interruption of an antiretroviral treatment (ART) initiated during primary HIV-1 infection (PHI) is rare and the frequency and predictive factors of such a control are unknown., Methods: Within the French ANRS PRIMO Cohort, 164 patients interrupted ART initiated during PHI. We compared patients whose viral load (VL) remained undetectable (<50 copies/ml) or low (50-500 copies/ml) 1 year after ART interruption to those who evidenced a rapid viral rebound., Results: After ART interruption, VL remained undetectable for a median time of 4.5 years in 14 patients ('post-ART controllers') and low in another 14 patients for a median time of 1.5 years. Post-ART controllers also maintained higher CD4(+) T-cell counts compared to other patients. Female gender, a high CD4(+) T-cell count and low VL during PHI, and a high CD4(+) T-cell count and low HIV DNA levels at interruption, were associated with post-ART HIV control. Treatment characteristics did not differ between controllers and non-controllers. Post-ART controllers had lower specific CD8(+) T-cell frequencies and CD8(+) T-cell activation on ART and after ART interruption than non-controllers., Conclusions: Few patients maintain very low VL after interruption of treatment initiated during PHI. Early patient characteristics were the main factors of viral control, although early initiation of ART and the effect of ART on reservoir might contribute to control.

CD8(+) T cells play an important role in controlling viral infections. Defective CD8(+) T-cell responses during HIV infection could contribute to viral persistence. Early initiation of highly active antiretroviral therapy during acute primary HIV infection helps to preserve HIV-specific immune responses. Here, we describe a particular CD27(+) CD45RO(-)/RA(+) HIV-specific CD8(+) T cell in participants treated early during the primary infection. These cells, which were present at a very low frequency during primary HIV infection, increased markedly after early treatment, whereas their frequency remained unchanged in untreated participants and in participants treated later. These nonnaive antigen-experienced cells are in a resting state and have characteristics of long-lived memory cells. They also possess direct effector capabilities, such as cytokine production, and are able to proliferate and to acquire cytotoxic functions on reactivation. Our results suggest that these HIV-specific CD27(+) CD45RO(-)/RA(+) CD8(+) T cells, observed when early viral replication is inhibited, form a pool of resting cells with memory characteristics.

Objectives: To assess the influence of patient characteristics, treatment precocity (how early) and duration of sustained virological response to highly active antiretroviral therapy (HAART) on HIV RNA levels after withdrawal of treatment started during primary infection and to compare HIV RNA levels after HAART withdrawal with levels reached at the same time point during the natural history of infection in the pre-HAART era., Design: HIV RNA was analysed using linear mixed-effects models for 58 patients from the PRIMO cohort (1996-2003) treated during primary infection (with sustained virological responses until HAART interruption) and 116 untreated patients enrolled in the SEROCO cohort within 6 months following infection (1988-1995). Viral loads were estimated in PRIMO patients 36 months after infection (12 months after treatment interruption) and were estimated for the SEROCO patients 36 months after infection, after adjustment for gender and age., Results: HIV RNA levels 12 months after HAART interruption were independently associated with levels at HAART initiation and with the CD4 cell count at HAART interruption, but not with the precocity of HAART or the duration of virological response to HAART. Thirty-six months after infection, mean HIV RNA levels were 3.95 log10 copies/ml 12 months after stopping HAART and 4.11 log10 copies/ml in never-treated patients., Conclusion: Viral load 12 months after withdrawal of transient effective HAART started during primary infection is similar to viral load at the same time after infection in never-treated patients, suggesting that early HAART initiation does not lower the virological set-point.

HIV-specific CD4+ T-helper cell responses in 40 subjects with chronic infection (CI) who had virus suppression after highly active antiretroviral therapy (HAART) were compared with those in 34 subjects treated during primary infection (PI). A CD4+ T-cell proliferative response to HIV p24 protein was present in 50% of these subjects compared with 79% of subjects treated during PI. The existence of a proliferative response in CI subjects was associated with a higher CD4+ T-cell count at initiation of HAART, a longer duration of virus suppression, and a higher CD4+ T-cell count at the time of analysis. These results show that an HIV-specific proliferative response is preferentially observed in treated CI subjects with CD4+ T-cell counts of >200/microL. However, in treated CI subjects with a significant degree of CD4+ T-cell depletion (<200/microL), it may also be observed in 35% provided that the duration of virus suppression is long enough, which may have implications for future therapeutic strategies.

Human immunodeficiency virus (HIV)-specific CD4(+) and CD8(+) T cell responses were evaluated prospectively in a large cohort of subjects with HIV primary infection via long-term follow-up examining different virological profiles related to different treatment interventions. No correlation was observed between baseline virus load and HIV-specific CD4(+) and CD8(+) T cell responses. Highly active antiretroviral therapy (HAART)-induced suppression of viremia was associated with an increase in CD4(+) T cell proliferative responses. The HIV-specific proliferative response also increased, at least in the first 18 months, in subjects with detectable viremia, either treated or untreated. The magnitude of the HIV-specific CD8(+) T cell response decreased with suppression of viremia. In subjects with detectable viremia, the breadth and magnitude of the HIV-specific CD8(+) T cell responses increased progressively. Finally, whether HAART was initiated before or after seroconversion had little effect on HIV-specific CD4(+) and CD8(+) T cell responses.