An ongoing dialogue on HIV/AIDS, infectious diseases,
May 2nd, 2010
Learning from Clinical Trials with Limited “Generalizability”
In the ongoing debate about when to start antiretroviral therapy in our sickest patients — those with acute opportunistic infections — comes this study from Zimbabwe of early vs. deferred ART in patients with cryptococcal meningitis:
The median durations of survival were 28 days and 637 days in the early and delayed ART groups, respectively (P
=
.031, by log‐rank test). The risk of mortality was almost 3 times as great in the early ART group versus the delayed ART group (adjusted hazard ratio, 2.85; 95% confidence interval, 1.1–7.23). The study was terminated early by the data safety monitoring committee.
In sum, early ART made a terrible situation even worse: 3-year survival for the early ART group was only 22%, vs 46% in the deferred therapy group.
The challenges of applying this study to clinical practice here are numerous, including use of non-amphotericin therapy for cryptococcal CNS disease, lack of protocol-directed management of suspected raised intracranial pressure or immune reconstitution inflammatory syndrome (IRIS), and the highly unstable social and political situation in the country at that time.
Still — sometimes a study’s findings are so overwhelming that that there is something to be learned, issues of limited generalizabilty notwithstanding.
I suspect here it’s that ART should be deferred for at least a couple of weeks in patients with crytpotoccal meningitis, giving the amphotericin/5FC time to bring down the organism burden. Importantly, this slight delay would still be consistent with the “early” ART strategy of A5164, where the median time to start therapy was 12 days after OI treatment.
At least that’s what I’ll be doing until the results of this study are available.
Paul E. Sax, MD
Associate Editor
NEJM Clinician
Biography | Disclosures & Summaries
Learn more about HIV and ID Observations.
FROM NEJM — Recent Infectious Disease Articles- Clusters of Concern — Spatial Link between Childhood Undervaccination and Measles Outbreaks in South Carolina May 20, 2026Spatial analysis in South Carolina revealed that measles infections were clustered in areas where public school vaccination rates were lower.
- Andes Hantavirus Outbreak on a Cruise Ship, 2026 May 20, 2026On May 2, hantavirus infection was diagnosed in a patient who had been on a cruise ship. Subsequent evaluation revealed multiple cases of Andes hantavirus infection on the ship. To date, three associated deaths have occurred.
- Childhood Vaccine Hesitancy May 20, 2026Vaccine hesitancy is often driven by safety concerns. Clinician recommendations, presumptive communication, and empathy improve uptake; maintaining trust supports future acceptance and community protection.
- Cerebral Syphilitic Gumma May 14, 2026A 50-year-old man presented to the ED with a 1-month history of headache and worsening weakness of the left arm and leg. Brain MRI showed an enhancing lesion with extensive surrounding edema.
- Ensitrelvir for Covid-19 Postexposure Prophylaxis in Household Contacts May 14, 2026In a trial, the 3C-like protease inhibitor ensitrelvir was more effective than placebo in preventing Covid-19 in household contacts of patients with SARS-CoV-2 infection.
- Clusters of Concern — Spatial Link between Childhood Undervaccination and Measles Outbreaks in South Carolina May 20, 2026