Despite being highly diverse, immunovirological status strongly correlates with clinical symptoms during primary HIV-1 infection: a cross-sectional study based on 674 patients enrolled in the ANRS CO 06 PRIMO cohort.

OBJECTIVES: To analyse immunovirological status during primary HIV-1 infection (PHI) according to contemporary clinical status and time since infection. METHODS: Plasma HIV-RNA and peripheral blood mononuclear cell (PBMC) HIV-DNA levels and CD4 cell counts were determined at enrolment in the ANRS PRIMO cohort. Time since infection was estimated based on both the number of antibodies on western blot at enrolment (0-1, 2-4 or > or =5 specific antibodies) and the estimated interval between infection and enrolment based on clinical and epidemiological features. Patients were classified according to the presence or absence of clinical symptoms at enrolment. RESULTS: Between 1996 and 2006, 674 patients were enrolled an estimated median of 47 days after infection. Median marker values were as follows: HIV-RNA 5.10 log(10) copies/mL (range <1.70-8.33); HIV-DNA 3.30 log(10) copies/10(6) PBMCs (<1.84-4.93); and 506 CD4 cells/mm(3) (40-1542). Median HIV-RNA and PBMC HIV-DNA levels were significantly higher in patients with 0 or 1 specific antibody (n = 71) than in patients with 2-4 (n = 228) or > or =5 antibodies (n = 375). Symptomatic patients had significantly higher HIV-RNA and PBMC HIV-DNA levels and lower CD4 cell counts. However, 10% of symptomatic patients recruited shortly after infection had favourable immunovirological status. CONCLUSIONS: Plasma HIV-RNA, PBMC HIV-DNA and CD4 cell count values were highly diverse and correlated strongly with clinical status during PHI. Early diagnosis was not always associated with severe PHI. Combining PBMC HIV-DNA with HIV-RNA, CD4 cell count and clinical symptoms would have allowed identification of 179 patients (26.5%) at high risk of rapid disease progression who did not meet current guidelines for early treatment initiation.

Acute plasma biomarkers of T cell activation set-point levels and of disease progression in HIV-1 infection.

T cell activation levels, viral load and CD4(+) T cell counts at early stages of HIV-1 infection are predictive of the rate of progression towards AIDS. We evaluated whether the inflammatory profile during primary HIV-1 infection is predictive of the virological and immunological set-points and of disease progression. We quantified 28 plasma proteins during acute and post-acute HIV-1 infection in individuals with known disease progression profiles. Forty-six untreated patients, enrolled during primary HIV-1 infection, were categorized into rapid progressors, progressors and slow progressors according to their spontaneous progression profile over 42 months of follow-up. Already during primary infection, rapid progressors showed a higher number of increased plasma proteins than progressors or slow progressors. The plasma levels of TGF-ß1 and IL-18 in primary HIV-1 infection were both positively associated with T cell activation level at set-point (6 months after acute infection) and together able to predict 74% of the T cell activation variation at set-point. Plasma IP-10 was positively and negatively associated with, respectively, T cell activation and CD4(+) T cell counts at set-point and capable to predict 30% of the CD4(+) T cell count variation at set-point. Moreover, plasma IP-10 levels during primary infection were predictive of rapid progression. In primary infection, IP-10 was an even better predictor of rapid disease progression than viremia or CD4(+) T cell levels at this time point. The superior predictive capacity of IP-10 was confirmed in an independent group of 88 HIV-1 infected individuals. Altogether, this study shows that the inflammatory profile in primary HIV-1 infection is associated with T cell activation levels and CD4(+) T cell counts at set-point. Plasma IP-10 levels were of strong predictive value for rapid disease progression. The data suggest IP-10 being an earlier marker of disease progression than CD4(+) T cell counts or viremia levels.