Development of AntiRetroviral Therapy in Africa (DART) study post hoc safety data analysis comparing safety outcomes of study participants with baseline creatinine clearance of 30-49 mL/min vs participants with creatinine clearance of ≥50 mL/min

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Not applicable
• If ‘Not applicable’, further details on the study type:
  Post hoc analysis of specific safety outcomes obtained from the previously completed interventional Medical Research Council Sponsored DART study
• If ‘other’, further details on the scope of the study:
  Post-hoc analyses of 96 week safety outcome comparison of study participants with baseline creatinine clearance (CLcr) of 30-49 mL/min vs participants with CLcr of ≥50 mL/min from the open-label Development of AntiRetroviral Therapy in Africa trial

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  LAMIVUDINE

  ZIDOVUDINE

  ABACAVIR

  NEVIRAPINE

  TENOFOVIR
• Medical condition to be studied:
  HIV infection

Population studied

• Short description of the study population:
  Patients aged 18 years or older with HIV infection in Africa.; Inclusion criteria: ; 1. Documentation of HIV-1 infection: antibody positive serology by ELISA test (confirmed by licensed second ELISA or Western Blot). ; 2. Age > 18 years ; 3. Symptomatic WHO stage 2, 3 or 4 HIV disease and CD4 < 200 cells/mm3; 4. ART naïve (except for ART use during pregnancy for the prevention of mother-to-child HIV transmission). ; 5. Agreement and documented informed consent to be randomised to CMO or LCM and to STI or continuous ART, if eligible. ; 6. Life expectancy of at least 3 months; ; Exclusion criteria:; 1. Cannot, or unlikely to attend regularly (e.g. usual residence too far from Study Centre) ; 2. Likelihood of poor compliance ; 3. Presence of acute infection (e.g. malaria, acute hepatitis, pneumococcal pneumonia, non-typhoid salmonella septicaemia, cryptococcal meningitis). Patients may be admitted after recovery of an acute infection. Patients with tuberculosis (TB) will not be enrolled while on the intensive phase of anti-tuberculosis therapy, but should be re-evaluated after the intensive phase and a decision made then about starting ART. Patients starting ART whilst on anti-tuberculosis therapy after the intensive phase will not receive NVP, nor will they be randomised into the NORA substudy. ; 4. On chemotherapy for malignancy ; 5. Laboratory abnormalities which are a contra-indication for the patient to start ART (e.g. Haemoglobin <8g/dl, neutrophils <0.50x109/l, AST or ALT >5 x the upper limit of normal (ULN), grade 3 renal dysfunction - creatinine >360 mol/l and/or urea >5 x ; ULN). ; 6. Pregnancy or breast-feeding
• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Immunocompromised

  Other
• Special population of interest, other:
  Patients with HIV infection
• Estimated number of subjects:
  3316

Study design details

• Main study objective:
  To describe the post-hoc analyses for the 96 week safety outcome comparison of study participants with baseline creatinine clearance (CLcr) of 30-49 mL/min vs participants with CLcr of ≥50 mL/min from the open-label Development of AntiRetroviral Therapy in Africa trial (DART).
• Outcomes:
  Safety events, effect of ART initiation on renal function over 96 weeks.
• Data analysis plan:
  Descriptive statistics were used to compare safety outcomes over a period of 96 weeks for study participants that entered the study with baseline renal function of CLcr 30-49 mL/min to those with baseline CLcr ≥50 mL/min. The adverse event rates for common adverse events for participants treated with any antiretroviral drug with baseline CLcr 30-49 mL/min and those with baseline CLcr ≥50 mL/min) were evaluated and the relative risk and 95% confidence intervals were presented. This was not a powered study and no multiple comparisons were adjusted.