The patients were well enough to give informed consent and to take oral medications, and therefore the findings may not be generalizable to those who are severely unwell or requiring intensive care. Previous observational data suggest a survival benefit for HIV-positive patients who are started on ART while in the intensive care unit [3, 4], but the data are insufficient to make
a recommendation in this group [3, 4]. There was no increase in the incidence of immune reconstitution disorders (IRD) or adverse events generally with early ART initiation in ACTG 5164 [1,5]. However, those with intracranial selleck chemical opportunistic infections (such as cryptococcal meningitis [6]) may be more prone to severe IRDs with early ART initiation and increased observation of these patients may be warranted (although it is still recommended to initiate ART about 2 weeks after the commencement of opportunistic infection therapy assuming the patient is stable). Those presenting with TB 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 Ribonucleotide reductase be destroyed Obeticholic Acid by uncontrolled viral replication, the presence of which is associated with survival in untreated individuals [1]. Reduction in morbidity associated with high viraemia and profound CD4 cell depletion during acute infection [2-4]. Reduction in the enhanced risk of onward transmission of HIV associated with PHI [5-10]. 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 evidence for this effect of treatment in primary infection). Data from the CASCADE collaboration [11] 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 [12, 13].