Background: HIV antiretroviral therapy (ART) is often managed without routine laboratory monitoring in Africa; however, the effect of this approach is unknown. This trial investigated whether routine toxicity and efficacy monitoring of HIV-infected patients receiving ART had an important long-term effect on clinical outcomes in Africa. Methods: In this open, non-inferiority trial in three centres in Uganda and one in Zimbabwe, 3321 symptomatic, ART-naive, HIV-infected adults who had CD4 counts less than 200 cells per μL and were starting ART were randomly assigned to laboratory and clinical monitoring (LCM; n=1659) or clinically driven monitoring (CDM; n=1662) by a computer-generated list. Haematology, biochemistry, and CD4 cell counts were done every 12 weeks. In the LCM group, results were available to clinicians; in the CDM group, results (apart from CD4-cell count) could be requested if clinically indicated and grade 4 toxicities were available. Participants switched to second-line ART after new or recurrent WHO stage 4 events (in both groups), or CD4 count less than 100 cells per μL (LCM only). Co-primary endpoints were new WHO stage 4 HIV events or death, and serious adverse events. Non-inferiority was defined as the upper 95% confidence limit for the hazard ratio (HR) for new WHO stage 4 events or death being no greater than 1·18. Analyses were by intention to treat. This study is registered, number ISRCTN13968779. Findings: Two participants assigned to CDM and three to LCM were excluded from analyses. 5-year survival was 87% (95% CI 85—88) in the CDM group and 90% (88—91) in the LCM group, and 122 (7%) and 112 (7%) participants, respectively, were lost to follow-up over a median of 4·9 years of follow-up. 459 (28%) participants receiving CDM versus 356 (21%) LCM had a new WHO stage 4 event or died (6·94 [95% CI 6·33—7·60] vs 5·24 [4·72—5·81] per 100 person-years; absolute difference 1·70 per 100 person-years [0·87—2·54]; HR 1·31 [1·14—1·51]; p=0·0001). Differences in disease progression occurred from the third year on ART, whereas higher rates of switch to second-line treatment occurred in LCM from the second year. 283 (17%) participants receiving CDM versus 260 (16%) LCM had a new serious adverse event (HR 1·12 [0·94—1·32]; p=0·19), with anaemia the most common (76 vs 61 cases). Interpretation: ART can be delivered safely without routine laboratory monitoring for toxic effects, but differences in disease progression suggest a role for monitoring of CD4-cell count from the second year of ART to guide the switch to second-line treatment.
The Lancet (2010) 375 (9709) 123-131 [doi:10.1016/S0140-6736(09)62067-5]