Early initiation of antiretroviral therapy (ART) among patients with HIV and cryptococcal meningitis coinfection is not associated with increased risk of mortality, according to study findings published in Clinical Infectious Diseases.

Researchers used pooled data to mimic a randomized clinical trial (RCT) using a marginal structural model to test the effect of early vs late ART initiation on the risk of all-cause mortality among HIV-positive patients diagnosed with cryptococcal meningitis coinfection. Early ART initiation was defined as receipt within 14 days of diagnosis and late ART initiation was defined as receipt 25 to 56 days after diagnosis.

Data captured from 190 patients were included in the analysis, of whom 82.6% were men, the median age was 38 (IQR, 33-44) years, and 37.9% acquired HIV infection through heterosexual intercourse and 34.2% through homosexual intercourse. In addition, 41.1% had a previous AIDS diagnosis, the median CD4+ T-cell count and HIV viral load at cryptococcal meningitis diagnosis was 19 (IQR, 10.56) cells/mm3 and 5.3 (IQR, 4.9-5.6) log10 copies/mL, respectively, and 76% used ART within the previous 6 months.

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Overall, mortality occurred among 33 patients 6 months after cryptococcal meningitis diagnosis. Patients who died vs survived were older (median age, 43 vs 38 years; P =.021) and had lower rates of ART use within the previous 6 months (8% vs 92%; P <.01). Of note, mortality occurred among more patients in the late ART group (n=20) compared with those in the early ART group (n=13).

Mortality was most commonly attributed to AIDS-defining events (45.5%), followed by unknown cause (42.4%) and non-AIDS defining events (12.1%).

Among patients in the early and late ART groups, 69.6% and 51.5% initiated protease inhibitor-based ART, 25.0% and 42.7% initiated non-nucleoside reverse transcriptase inhibitor-based ART, 1.8% and 1.5% initiated nucleoside reverse transcriptase inhibitor-based ART, and 3.6% and 4.4% initiated other types of ART, respectively.

In a Kaplan-Meier survival analysis, survival rates did not significantly differ between the early and late ART groups (P =.4379). After adjustments for time and baseline variables, pooled logistic regression showed an adjusted hazard ratio for mortality of 1.40 (95% CI, 0.66-2.95) among late vs early ART initiators.

This study was limited by its design, the small sample size, and the lack of data on clinical characteristics.

The study authors concluded, “We did not find evidence that early ART within two weeks of CM [cryptococcal meningitis] diagnosis led to higher mortality among PWH [people with HIV] presenting with CM in high income settings.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Ingle SM, Miro JM, May MT, et al. Early antiretroviral therapy not associated with higher cryptococcal meningitis mortality in people with HIV in high-income countries: an international collaborative cohort study. Clin Infect Dis. Published online March 8, 2023. doi:10.1093/cid/ciad122

This article originally appeared on Infectious Disease Advisor