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Abstract
Clinical correlations of inflammatory cytokines in the female genital tract during acute HIV-1 infection
L. Bebell1, J.-A. Passmore2, C. Williamson3, K. Mlisana4, I. Iriogbe4, Q. Abdool Karim4, S.A. Karim4, and the CAPRISA Acute Infection Study Team
1Columbia University College of Physicians and Surgeons, Centre for the AIDS Programme of Research in South Africa, Durban, South Africa, 2University of Cape Town, Division of Medical Virology, Department of Laboratory Sciences, Cape Town, South Africa, 3University of Cape Town, Division of Medical Virology, Institute of Infectious Diseases and Molecular Medicine, Cape Town, South Africa, 4University of KwaZulu Natal, Centre for the AIDS Programme of Research in South Africa, Durban, South Africa
Background:
Causal relationships between cytokines in acute HIV infection and clinical symptoms or disease progression have not been investigated, nor have cytokine profiles in the genital tract. Understanding the compartmental immune response may provide clues to understanding HIV pathogenesis, the impact of concurrent STIs, and design of future microbicides and vaccines. We evaluated inflammatory cytokines in cervicovaginal lavage (CVL) and plasma in acute HIV-1 and their relationship to clinical outcomes.
Methods:
Matched CVL and plasma samples were obtained from nineteen women with acute HIV at 22-62 days post-infection. Participants are sex workers followed up monthly as part of CAPRISA 002, a cohort study on immunological events in acute infection. Levels of IL-1b, IL-6, IL-8, IL-10, IL-12, and TNF-a were measured using the BD Human Inflammation Cytometric Bead Array Kit. Clinical signs and symptoms were evaluated using the CAPRISA Clinical Checklist administered by study clinicians.
Results:
Of eight participants evaluated for clinical symptoms, the three symptomatic women had elevated total CVL cytokine compared to the five asymptomatic women. Four of fifteen participants followed for seven months progressed to CD4+ cell counts less than 350 cells/uL. These four rapid progressors had higher levels of TNF-a (6.0pg/mL vs. 2.0pg/mL), IL-10 (1.6vs.0.8), IL-6 (93.8vs.30.3), IL-1b (341.0vs.143.3), and IL-8 (1793vs.1212) in CVL compared to other participants, but lower levels of IL-12 (0.7vs.1.1). Participants with bacterial vaginosis (BV) (n=16) had significantly higher levels of IL-8 (3997 vs. 581, p=0.033) and lower IL-10 (0.0vs.2.9, p=0.07) in the CVL compared to BV negatives (n=3). Levels of all cytokines except IL-10 were significantly elevated in CVL compared with plasma (p<0.001 to 0.05).
Conclusions:
Elevated CVL cytokines in acute HIV may be associated with rapid disease progression. Women co-infected with acute HIV and BV also have higher cytokine levels. Further research will focus on defining the relationship of CVL cytokines to local genital tract pathogenesis.
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