Virologic failure was less likely in the efavirenz group than in the lopinavir-ritonavir group. The virologic efficacy of the NRTI-sparing regimen was similar to that of the efavirenz regimen but was more likely to be associated with drug resistance. (ClinicalTrials.gov number, NCT00050895 [ClinicalTrials.gov].).
Background
Antiretroviral therapy (ART) is indicated during tuberculosis (TB) treatment of patients infected with HIV-1, but the urgency to start ART at TB diagnosis for patients of varying levels of immune compromise is not known.
Methods
We conducted an open label, randomized study comparing immediate (within 2 weeks of TB treatment initiation) to early (8–12 weeks) ART among HIV-1 infected patients with CD4+ lymphocytes < 250/mm3 and suspected TB. The primary study endpoint was proportion of patients who survived without an AIDS-defining illness at 48 weeks.
Results
809 patients with median baseline CD4+ lymphocytes of 77 cells/mm3 and HIV-1 RNA of 5.43 log10 copies/mL were enrolled. In the immediate arm, 12.9% of patients experienced an AIDS-defining illness or death by 48 weeks compared to 16.1% in the early arm (p=0.45; 95% confidence interval (CI) for difference: −1.8%, 8.1%). In patients with screening CD4+ lymphocytes <50 cells/mm3, 15.5% of patients on the immediate arm vs. 26.6% on early ART experienced an AIDS defining illness or death (p=0.02; difference CI: 1.5%, 20.5%). TB immune reconstitution inflammatory syndrome (IRIS) was more common with immediate ART (11% vs. 5%: p=0.002). Viral suppression at 48 weeks was 74% and did not differ between arms (p=0.38).
Conclusion
Overall, immediate ART did not reduce AIDS-defining illnesses and death compared to early ART. For persons with CD4+ lymphocytes < 50 cells/mm3, immediate ART had 42% less AIDS defining illnesses and death compared to early ART. (ClinicalTrial.gov number NCT00108862.)
Background
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
variants threatens progress toward control of the Covid-19 pandemic. Evaluation of
Covid-19 vaccine efficacy against SARS-CoV-2 variants is urgently needed to inform
vaccine development and use.
Methods
In this phase 2a/b, multicenter, randomized, observer-blinded,
placebo-controlled trial in South Africa, healthy human immunodeficiency virus
(HIV)-negative adults (18 to 84 years) or medically stable people living with HIV (PLWH)
(18 to 84 years) were randomized in a 1:1 ratio to receive two doses, administered 21
days apart, of either NVX-CoV2373 nanoparticle vaccine (5 μg recombinant spike
protein with 50 μg Matrix-M1 adjuvant) or placebo. The primary endpoints were
safety and vaccine efficacy ≥7 days following the second dose against
laboratory-confirmed symptomatic Covid-19 in previously SARS-CoV-2 uninfected
participants.
Results
A total of 4387 participants were randomized and dosed at least once, 2199 with
NVX-CoV2373 and 2188 with placebo. Approximately 30% of participants were seropositive
at baseline. Among 2684 baseline seronegative participants (94% HIV-negative; 6% PLWH),
15 and 29 predominantly mild to moderate Covid-19 cases were noted in NVX-CoV2373 and
placebo recipients, respectively; vaccine efficacy was 49.4% (95% confidence interval
[CI]: 6.1 to 72.8). Efficacy in HIV-negative participants was 60.1% (95% CI: 19.9 to
80.1) and did not differ by baseline serostatus; 38 (92.7%) of 41 sequenced cases were
the B.1.351 variant. Post-hoc vaccine efficacy against B.1.351 was 51.0% (95% CI:
−0.6 to 76.2) in HIV-negative participants. Preliminary local and systemic
reactogenicity were primarily mild to moderate and transient, and higher with
NVX-CoV2373; serious adverse events were rare in both groups.
Conclusions
The NVX-CoV2373 vaccine was efficacious in preventing Covid-19, which was
predominantly mild to moderate and due to the B.1.351 variant.
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