| Methods |
Patients (n = 43) were randomized at baseline to receive treatment in 1 of 2 dosing regimens: patients in the intervention (or PRC) group (n = 22) were assigned to take Stavudine d4T PRC/3TC/EFV all once daily (24 hours apart) and patients in the usual care group (n = 21) were assigned to continue the twice daily version of d4T (IR/3TC/EFV or Combivirs/EFV) as per their screening regimen |
| Participants |
Patients were over 18 years of age and weighed over 40 kilograms. Patients were excluded from this study if they were pregnant (in women of childbearing potential, consent was obtained to ensure they used 2 effective forms of contraception and regularly underwent urinary pregnancy testing), they had proven or suspected hepatitis, an active AIDS‐defining disease, a history of bilateral peripheral neuropathy or signs of bilateral peripheral neuropathy of grade 2 or higher |
| Interventions |
This intervention involved simplifying the dosage for a nucleoside reverse transcriptase inhibitor (NRTI) from twice daily to once daily. Patients in the intervention group were assigned to take Stavudine d4T PRC/3TC/EFV all once daily (24 hours apart). Control group patients continued either d4T IR/3TC/EFV or Combivirs/EFV as per their screening regimen |
| Outcomes |
Compliance was measured using the information obtained from Medication Event Monitoring System (MEMS) caps given with the medication and downloaded at baseline, week 12 and week 24 visits. 3 compliance summary variables were computed: 1) taking compliance, the percentage of prescribed number of doses taken; 2) correct dosing compliance, the percentage of days with correct number of doses taken; and 3) timing compliance, the percentage of doses taken within + 3 hours of the prescribed dosing intervals. At each visit, a clinical history was taken and a clinical examination was performed that entailed searching for symptoms of peripheral neuropathy, an examination of peripheral sensation, motor power and reflexes, checking viral load, total lymphocyte and subset analysis, full blood counts and measurements of serum transaminases (including gamma glutamyl transferase (g‐GT), serum amylase, lactate and anion gap), total cholesterol, triglycerides, low‐density lipoproteins (LDL), high‐density lipoproteins (HDL), serum electrolytes, and urea and creatinine. At baseline, week 12 and week 24, a quality of life assessment was made using a Medical Outcomes Study HIV Health Survey (MOS‐HIV) questionnaire |
| Notes |
― |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Unclear risk |
Randomization was not described in detail. "A screening visit 4 weeks prior to randomization; a baseline visit where 1:1 randomization to switch to d4T PRC 100mg and once‐daily therapy or to continue their current therapy took place; and follow‐up at weeks 12 and 24. Subjects were randomly allocated at baseline to receive treatment in one of two dosing regimens." (pg 186) |
| Allocation concealment (selection bias) |
Unclear risk |
No information was provided about how allocation was handled |
| Selective reporting (reporting bias) |
Unclear risk |
No protocol available; although it appears that everything was reported it is difficult to determine this without a protocol |
| Other bias |
Unclear risk |
Study population already had 98.5% adherence ‐ raises doubts regarding selection of subjects. There is no mention of the study site, whether all patients were offered participation. Also, adherence level is not included as an inclusion criterion |
| Blinding of outcome assessment (detection bias)
Adherence measure |
Unclear risk |
(PRIMARY) MEMS ‐ Open‐label study. Not clear who were involved in collecting data, but the data download was done remotely. Insufficient information. There is insufficient information to permit judgment of 'Low risk' or 'High risk' |
| Blinding of outcome assessment (detection bias)
Patient outcome |
Low risk |
(PRIMARY) VIRAL LOAD ‐ This is an objective measure of outcome |
| Blinding of participants (performance bias)
Adherence measure |
High risk |
(PRIMARY) MEMS ‐ No mention of patient blinding. Blinding of patient/participant attempted, but likely that the blinding could have been broken, and the outcome is likely to be influenced by lack of blinding |
| Blinding of participants (performance bias)
Patient outcome |
Low risk |
(PRIMARY) VIRAL LOAD ‐ This is an objective measure of outcome |
| Blinding of personnel (performance bias)
Adherence measure |
Unclear risk |
(PRIMARY) MEMS ‐ No information on blinding given. There is insufficient information to permit judgment of 'Low risk' or 'High risk' |
| Blinding of personnel (performance bias)
Patient outcome |
Low risk |
(PRIMARY) VIRAL LOAD ‐ This is an objective measure of outcome |
| Incomplete outcome data (attrition bias)
Adherence measure |
Low risk |
(PRIMARY) MEMS ‐ Missing outcome balanced across groups |
| Incomplete outcome data (attrition bias)
Patient outcome |
Low risk |
(PRIMARY) VIRAL LOAD ‐ Missing outcome balanced across groups |
