Dissecting the effects of filarial-associated immunomodulation on HIV susceptibility

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The rapid spread of HIV over the last decades in Sub-Saharan Africa has led to different hypotheses to explain this phenomenon. One well-known hypothesis implies that specific pre-existing helminth infections contribute to systemic immune activation, which facilitates early viral dissemination hence increases susceptibility to HIV. In a recent prospective study in Tanzania, our consortium have demonstrated, for the first time, that there is a significant increased risk of acquiring HIV in individuals presenting lymphatic filariasis (LF), especially in 14-30 year olds. LF is known to induce immune-regulation in the host and preliminary findings from this consortium have shown that LF-infected individuals have increased frequencies of activated CD4+ T cells whereas CD8+ T cells showed markers of exhaustion. Interestingly, exhausted CD8+ T cells were only found in patent individuals, those with peripheral microfilaria (MF), the worms offspring. This study will continue to investigate immune-epidemiological associations of LF and HIV in endemic areas of Ghana and Tanzania. First, a follow up study with same Tanzanian cohort will determine the effects of long-term mass drug administration (MDA) on HIV incidence. Since MDA was applied only after the initial study began we are in a unique position to address this question and moreover, decipher immunological changes in this cohort in a longitudinal manner. Further field studies in Ghana will assess the prevalence of HIV in endemic areas of LF and onchocerciasis providing information about whether the increased susceptibility is restricted to LF infections or a phenomenon of filariae per se. Furthermore, by sub-dividing the LF-infected individuals into infection state (MF+ vs. MF-), we will determine whether the observed association is MF-dependent and moreover, through immune profiling gain new insights into filarial-induced mechanisms that drive enhanced susceptibility. Finally, in vitro PBMC stimulation using transgenic HSA-HIV strains and antigens derived from different filarial species, immune responses in different infection scenarios will be analyzed. In summary, this study aims to elucidate the mechanisms underlying the increased susceptibility for HIV in LF-infected individuals and will provide novel insights into parasite-host-virus interactions.