On Monday and Wednesday, Megan and Jack presented cases of patients with uncontrolled/newly diagnosed HIV who presented with PJP pneumonia. One question that came up was, when do we start antiretroviral therapy (ART) in these patients?
For the most part, the answer is immediately. Early ART initiation results in less AIDS progression and death with little increase in adverse events. An RCT published in 2009 in PLoS ONE evaluated almost 300 subjects who presented with either an AIDS-defining opportunistic infection (OI) OR serious bacterial infection (BI) + CD4 < 200 (1). People were randomized either to immediate start of ART or deferred start after treatment of OI was completed. The breakdown of infections among patients was: 63% PJP, 12% cryptococcal meningitis, and 12% bacterial infections. The study found that 14% of patients in the early arm had progression of disease or died, compared to 24% of patients in the deferred arm. Median time to ART was 12 days after OI treatment in the early arm and 45 days after OI treatment in the deferred arm. Rates of confirmed immune reconstitution inflammatory syndrome (IRIS) were at 5.7% for the early arm and 8.5% for the deferred arm and was not statistically significant.
The primary exception to starting immediately is in a patient with cryptococcal meningoencephalitis. The trial described above was not powered to look solely at patients with cryptococcal meningitis, and other trials looking at early versus delayed initiation of ART in patients with cryptococcal CNS disease consistently lower rates of survival and increased rates of IRIS with early initiation (2-4). ART is also frequently delayed in the setting of other CNS opportunistic infections (ex. CNS tuberculosis) although evidence is less robust here.
Takeaway: Initiate ART immediately in patients presenting with opportunistic infections (especially PJP) EXCEPT for those who have CNS cryptococcal disease, and consider delaying in other CNS infections such as tuberculosis. Have a low threshold to send a serum cryptococcal antigen in patients with HIV before starting ART, particularly those with neurological symptoms.
- Zolopa A, Andersen J, Powderly W, et al. Early antiretroviral therapy reduces AIDS progression/death in individuals with acute opportunistic infections: a multicenter randomized strategy trial. PLoS ONE. 2009;4(5):e5575.
- Makadzange AT, Ndhlovu CE, Takarinda K, et al. Early versus delayed initiation of antiretroviral therapy for concurrent HIV infection and cryptococcal meningitis in sub-saharan Africa. Clin Infect Dis. 2010;50(11):1532-8.
- Boulware DR, Meya DB, Muzoora C, et al. Timing of antiretroviral therapy after diagnosis of cryptococcal meningitis. N Engl J Med. 2014;370(26):2487-98.
- Bisson GP, Molefi M, Bellamy S, et al. Early versus delayed antiretroviral therapy and cerebrospinal fluid fungal clearance in adults with HIV and cryptococcal meningitis. Clin Infect Dis. 2013;56(8):1165-73.