The COAT study highlighted those with an acellular CSF and those with a

decreased Glasgow Coma Scale as being particularly prone to increased mortality with early ART initiation [23]. Those presenting with TB APO866 ic50 and malignancies are discussed in Section 8. We recommend patients presenting with PHI and meeting any one of the following criteria start ART: Neurological involvement (1D). Any AIDS-defining illness (1A). Confirmed CD4 cell count <350 cells/μL (1C). Proportion of patients presenting with PHI and neurological involvement, or an AIDS-defining illness or confirmed CD4 cell count <350 cells/μL started on ART. The scientific rationale for treating with ART in PHI is as follows. Preservation of specific anti-HIV CD4 T lymphocytes that would otherwise be destroyed by uncontrolled viral replication, the presence of which is associated with survival see more in untreated individuals [24]. Reduction in morbidity associated with high viraemia and profound CD4 cell depletion during acute infection [25-27]. Reduction in the enhanced risk of onward transmission of HIV associated with PHI [28-33]. Treatment of

patients with PHI who present with AIDS-defining illnesses, neurological disease or a CD4 cell count of <350 cells/μL is consistent with the recommendations for patients with chronic infection. The rationale for treating patients with neurological disease is that ART may lead to regression of otherwise irreversible neurological disease (although there is no high-quality 4-Aminobutyrate aminotransferase evidence for this effect of treatment in primary infection). Data from the CASCADE collaboration [34] showed that patients with primary infection, who had at least one CD4 cell count of <350 cells/μL in the first 6 months of infection, had a significantly greater mortality than those whose CD4 cell counts remained above this threshold, which supports early treatment in patients with lower CD4 cell counts. Multiple observational

studies have shown encouraging but inconclusive results following short-course ART initiated in PHI for individuals in whom ART would not otherwise be indicated [35, 36]. There have been three RCTs comparing the role of interrupted ART initiated in PHI on time to reach CD4 <350 cells/μL or the need for initiation of lifelong ART [37-39]. Overall there was a modest benefit in terms of delaying the decline in CD4 cell count, or time from seroconversion, to requiring initiation of lifelong ART following a 48- [39] or 60- [38] week course of ART. A post hoc analysis from the SPARTAC trial [39] showed a non-significant trend towards benefit in time to CD4 cell count <350 cells/μL when ART was initiated closer to the time of infection (HR 0.48; P = 0.09). This randomized study supported cohort studies in which a more rapid rate of CD4 cell loss was seen in individuals presenting within 12 weeks of a negative HIV antibody test [40, 41].