Rapid CD4+ cell decrease after transient cART initiated during primary HIV infection (ANRS PRIMO and SEROCO cohorts)

ArticleinJAIDS Journal of Acquired Immune Deficiency Syndromes 49(3):251-258 · November 2008with7 Reads
DOI: 10.1097/QAI.0b013e318189a739
Objective: To modelize the rate of CD4+ cell count decline and its determinants after cessation of combination antiretroviral therapy (cART) started during primary HIV infection (PHI) and compare it with never-treated patients. Methods: Kinetics of CD4+ counts were analyzed on the square root scale by using a mixed-effects model in 170 patients who received cART during PHI from the Primary Infection (PRIMO) cohort and 123 never-treated patients from the Seroconverters (SEROCO) cohort. Results: After cART interruption in the PRIMO cohort, the CD4+ cell count fell rapidly during the first 5 months and more slowly thereafter. The timing of treatment initiation had no influence on the rate of CD4+ cell decline. In contrast, a larger increase in CD4+ cell counts during cART was associated with a steeper decline and a larger loss of CD4+ cells after treatment interruption. The mean CD4+ cell loss 3 years postinterruption was 383 cells per microliter. In the SEROCO cohort, the CD4+ T-cell decline was less steep (3-year CD4+ loss 239 cells/μL). As a result, the mean CD4+ cell counts were similar (416 cells/μL) 3 years after cART interruption (PRIMO) or after infection (SEROCO). Conclusions: These data question the benefit of a limited course of cART even when initiated within 3 months after PHI diagnosis.
    • "Patient characteristics at the time of PHI were shown to greatly determine both the viral set point and the CD4 + T-cell loss after ART interruption. Results from this study also confirm the highly predictive value of early patient characteristics, which were associated with the level and frequency of viral control after interruption of ART initiated during PHI [4,8,16,23]. Spontaneous control has been observed in a few untreated patients followed since PHI diagnosis [24]. "
    [Show abstract] [Hide abstract] ABSTRACT: 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. 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. 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. 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.
    Full-text · Article · Aug 2012
  • [Show abstract] [Hide abstract] ABSTRACT: To clarify early correlates and natural history of HIV long-term nonprogressors (LTNPs) since HIV diagnosis. Patients enrolled in the French ANRS SEROCO/HEMOCO cohort with CD4 count >500 cells/mm3 at HIV diagnosis. LTNP status was defined as being asymptomatic, antiretroviral free, and with CD4 cell count >500 cells/mm3 for >8 years after HIV diagnosis. In LTNPs, we modeled the biological markers' progression through a joint model. Factors associated with loss of LTNP status were identified through a Cox model. Sixty (9%) of 664 patients were identified as LTNPs during follow-up. At enrollment, HIV RNA was <or=2.6 log copies/mL in 24% of LTNPs and HIV DNA was <or=1.85 log copies/10 peripheral blood mononuclear cells (PBMCs) in 31% vs. 3% and 8% in others. In LTNPs, HIV RNA and HIV DNA levels increased by 0.04 log copies/mL per year and 0.07 log copies/10(6) PBMCs per year during the first 8 years after diagnosis. LTNP status was lost in 36 subjects; baseline HIV DNA >1.85 log copies/10(6) PBMCs and high HIV DNA increase were associated with an increased risk of losing LTNP status [adjusted hazard ratio: 2.8 (1.2-6.8) and 2.2 (1.0-4.8), respectively]. LTNP status is established in the first years of HIV infection, low HIV DNA level at enrollment and slow increase of HIV DNA being associated with maintained LTNP status.
    Article · Jan 2009
  • [Show abstract] [Hide abstract] ABSTRACT: To investigate if early treatment of primary HIV-1 infection (PHI) reduces viral set point and/or increases CD4 lymphocytes. Analysis of two prospective multi-centre PHI cohorts. HIV-1 RNA and CD4 lymphocytes in patients with transient treatment were compared to those in untreated patients. Time to CD4 lymphocyte decrease below 350/ microl after treatment stop or seroconversion was calculated using Kaplan-Meier and Cox-PH-regression analyses. 156 cases of PHI were included, of which 100 had received transient HAART (median treatment time 9.5 months) and 56 remained untreated. Median viral load (563000 cop/ml vs 240000 cop/ml; p<0.001) and median CD4 lymphocyte (449/ microl vs. 613/ microl; p<0.01) differed significantly between treated and untreated patients. Median viral load was 38056 copies/ml in treated patients (12 months after treatment stop) and 52880 copies/ml in untreated patients (12 months after seroconversion; ns). Median CD4 lymphocyte change was +60/ microl vs. -86/ microl (p = 0.01). Median time until CD4 lymphocytes decreased to <350/ microl (including all patients with CD4 lymphocytes <500/ microl during seroconversion) was 20.7 months in treated patients after treatment stop and 8.3 months in untreated patents after seroconversion (p<0.01). Cox-PH analyses adjusting for baseline VL, CD4 lymphocytes, stage of early infection and symptoms confirmed these differences. Treatment during PHI did not lower viral set point. However, patients treated during seroconversion had an increase in CD4 lymphocytes, whereas untreated patients experienced a decrease in CD4 lymphocytes. Time until reaching CD4 lymphocytes <350/ microl was significantly shorter in untreated than in treated patients including patients with CD4 lymphocytes <500/ microl during seroconversion.
    Full-text · Article · Jul 2009
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