“In sub-Saharan Africa, 20-25 percent of patients with HIV infection present for care with severe immunosuppression. Among these patients, approximately 10 percent die during the first three months after ART initiation. Severe bacterial infection, tuberculosis, and cryptococcal infection play prominant roles in the cause of death in both children and adults. The development or exacerbation of such infections has been linked in part to the immune reconstitution inflammatory syndrome (IRIS) associated with the initiation of ART. Current guidelines recommend ruling out TB and cryptococcal meningitis before the initiation of ART, along with the use of trimethoprim–sulfamethoxazole and isoniazid prophylaxis. The risk of death increases markedly with decreasing CD4+ counts and body-mass index, suggesting the need for additional interventions aimed at preventing infection, accelerating immune recovery, and improving nutritional status.
One approach to preventing infection in all patients is administering preemptive treatment courses for specific high-burden diseases (e.g., TB) when ART is initiated. Another is an antimicrobial prophylaxis package targeting dominant pathogens among patients with advanced HIV infection after the clinical exclusion of active infections. In the Reduction of Early Mortality in HIV-Infected Adults and Children Starting Antiretroviral Therapy (REALITY) trial, researchers compared three interventions — enhanced antimicrobial prophylaxis, additional raltegravir, and food supplementation — to reduce early mortality in adults and older children with a CD4+ count of fewer than 100 cells per cubic millimeter in whom ART was initiated in four sub-Saharan African countries.”
