Zolopa 2009.
| Methods | Study design: open‐label RCT | |
| Participants |
Inclusion criteria: eligible participants were HIV‐positive men or women 13 years of age or older, presenting with an AIDS‐defining opportunistic infection or serious bacterial infection for which effective antimicrobial therapy was available and prescribed. To reflect clinical practice, the trial allowed presumptive and confirmed diagnoses as long as appropriate treatment for the opportunistic infection/bacterial infection had been initiated (cryptococcal disease was required to be confirmed). Participants in whom tuberculosis was diagnosed after randomization remained in the trial. Exclusion criteria: people with or on treatment for tuberculosis were excluded. People were ineligible if they had received ART within 8 weeks prior to study entry, more than 31 days of any ART within 6 months prior to study entry, or more than 1 ART regimen on which they experienced treatment failure. Number randomized: 35 Descriptive baseline data
Dropouts during study period: not reported for cryptococcal meningitis group |
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| Interventions |
Duration of antifungal therapy prior to randomization: <= 14 days Antifungal therapy provided: not reported Supportive care: not reported CSF pressure management: not reported ART regimen: choice of ART was left to the judgement of the clinician to better reflect common clinical practice. Early ART: 48 hours Delayed ART: 6 to 12 weeks Adherence: monitored by self reporting at 8, 16, 32, and 48 weeks |
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| Outcomes |
Primary outcome
Timing of outcome assessment: participants were seen at weeks 4, 8, 12, and 16 and every 8 weeks thereafter through week 48 for clinical assessments and routine laboratory monitoring. Participants in the deferred arm shifted to follow‐up at weeks 4, 8, 12, and 16 after initiation of ART and every 8 weeks thereafter until week 48. |
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| Notes |
Country: USA and South Africa Setting: 39 AIDS Clinical Trials Units in the USA (including Puerto Rico) and Johannesburg, South Africa (which was limited to enrolling 20 participants by the trial sponsor) Dates: May 2003 to August 2007 Funding: AIDS Clinical Trials Group funded by the National Institute of Allergy and Infectious Diseases Other: how cryptococcal meningitis was confirmed was not specified. |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | After eligibility checklist was completed, randomized treatment assignment was generated by central computer using permuted blocks within strata. |
| Allocation concealment (selection bias) | Low risk | Neither the size of the blocks nor treatment assignments to other sites were public, which prevented individual investigators from deducing the assignment pattern. |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | This was an open‐label trial. |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Assessment of adverse events was not blinded, which may have introduced bias for this outcome. |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Number of participants lost to follow‐up was not reported exactly, however the trial authors state: “Eighty‐seven percent of subjects, 123 in each arm, were evaluable for the primary endpoint”, suggesting that loss to follow‐up was 13% or less, which is acceptable. It is difficult to comment specifically on participants with cryptococcal meningitis, as these results were not disaggregated. |
| Selective reporting (reporting bias) | Unclear risk | The protocol was unavailable for evaluation. |
| Other bias | Unclear risk | As the trial had so little information on the participants in our treatment group of interest, it is difficult to comment on bias related to our trial population. |
Abbreviations: ART: antiretroviral therapy; CD4: cluster of differentiation 4; CFU: colony forming units; CNS: central nervous system; CrAg: cryptococcal antigen; CSF: cerebrospinal fluid; DAIDS: Division of AIDS; GCS: Glasgow coma score; HR: hazard ratio; IQR: interquartile range; IRIS: immune reconstitution inflammatory syndrome; LP: lumbar puncture; RCT: randomized controlled trial; SD: standard deviation; TDF: Tenofovir; FTC: Emtricitabine; EFV: Efavirenz; NVP: Nevirapine; AZT: Zidovudine; LFT: Liver function test