Netherlands Cohort Study on Acute HIV Infection

Rationale: There is renewed interest in finding a cure for HIV infection. Recent studies show that in a select group of individuals the initiation of combination anti-retroviral therapy (cART) during the early phase of infection results in long-term absence of viremia following treatment interruption after prolonged treatment. These patients are described as having achieved a "post-treatment viral remission". There are many unsolved issues regarding the question which virological and immunological factors determine which individuals achieve a "post-treatment viral remission". First studies suggest that the early reduction of viral reservoir size and potential accompanying preservation of immune function may be important factors. Furthermore, patients that initiate cART during acute infection are potential candidates for additional therapeutic strategies, such as latency reversing agents (LRAs) or therapeutic vaccination.

Objectives: The primary objective of the NOVA study is the establishment of a prospective cohort study of patients that initiate cART during the acute infection phase, aiming at achieving "post-treatment viral remission". The secondary objective is to characterize the viro-immunological factors that correlate with achievement of "post-treatment viral remission" for several years in these patients.

Study design: Prospective cohort study. Study population: The study population includes patients diagnosed with an AHI (Fiebig stage I-V, 20 in each stage). As a control group only for comparison of the lymph node viral reservoir and immune responses after 3 years of cART, 20 age-matched patients will be included who start cART in the chronic phase of infection. This control group is recruited to provide PBMCs and a LN sample for comparison purposes. Patients will be recruited over a period of 5 consecutive years.

Intervention: Patients diagnosed with an acute HIV infection (AHI) are offered immediate standard first-line cART. In consenting patients, at several time points samples will be obtained to analyze the size and characteristics of the viral reservoir and the accompanying immune function. Three groups are assembled based on the preparedness of individual patients to participate in the extensiveness of sampling. Patients that accept early treatment and follow-up but decline additional blood and tissue sampling (lymph node, GALT and cerebral spinal fluid (CSF)) are included in group 1 ("standard") and only routine diagnostic procedures are performed. Patients willing to undergo, in addition to routine monitoring, leukapheresis, semen and blood sampling for PBMC and virological analyses are included in group 2 ("less-invasive"). In group 3 ("extended") additional tissue and CSF sampling will be performed for the proposed viro-immunological analyses.

Main study parameters / endpoints: We will investigate the size, variability and localization of the (pro) viral reservoir and the properties of HIV-specific immune response and relate these to "post-treatment viral remission' achievement and / or duration. In addition we will study the factors that determine latency in the different host cells, their sensitivity to induction of replication competent virus by various agents and the potential application of these agents in "post-treatment viral remission".