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- Cerebral Syphilitic Gumma May 9, 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.
- Efficacy and Safety of an mRNA Seasonal Influenza Vaccine in Adults May 7, 2026Among adults 50 years of age or older, fewer cases of confirmed influenza-like illness were observed with an mRNA influenza vaccine than with standard vaccines. Reactogenicity was higher with the mRNA vaccine.
- Human Infection with Highly Pathogenic Avian Influenza A(H5N5) Virus May 7, 2026Avian influenza can jump species from birds to humans, a fact that arouses concern for serious illness and broader human transmission. In this report, avian influenza A(H5N5) was shown to cause severe human illness.
- Reducing Bacterial Contamination of Blood Bags with a Double Knot May 7, 2026In a study involving 180 blood bags, use of a double-knot closure rather than the usual single knot prevented bacterial contamination. This strategy may reduce the risk of blood-product contamination in resource-limited settings.
- Immune Interference May 7, 2026A 62-year-old man was admitted to the hospital for malaise, anorexia, rash, and diffuse lymphadenopathy. Fatigue and anorexia began 6 months earlier. Four months before admission, a pruritic rash developed on the back and spread.
- Cerebral Syphilitic Gumma May 9, 2026