However, the DART Trial Team study also found that 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.
ART is often managed without routine laboratory monitoring in Africa; however, the effect of this approach is unknown. In this study, the authors investigated whether routine toxicity and efficacy monitoring of HIV-infected patients receiving ART had an important long-term effect on clinical outcomes in Africa.
This randomised trial took place in three centres in Uganda and one in Zimbabwe. A total of 3321 symptomatic, ART-naive, HIV-infected adults with CD4 counts less than 200 starting ART were randomly assigned to laboratory and clinical monitoring or clinically driven monitoring.
In total, 3316 of these patients were included in the analysis. Haematology, biochemistry, and CD4-cell counts were done every 12 weeks. In the laboratory group, all laboratory results were available to clinicians; in the clinic group, results (apart from CD4-cell count) could be requested if clinically indicated and in the event of serious (grade 4) toxicity events occurring.
Participants switched to second-line ART after new or recurrent WHO clinical stage 4 events in both groups, or CD4 count less than 100.
The authors found that 5-year survival was 87% in the clinic group and 90% in the laboratory group, and 7% of participants in both groups were lost during the median follow-up of almost five years.
459 (28%) participants receiving clinic monitoring versus 356 (21%) laboratory monitoring had a new WHO stage 4 event or died. Differences in disease progression occurred from the third year on ART, whereas higher rates of switch to second-line treatment occurred in laboratory from the second year. 283 (17%) participants receiving clinic monitoring versus 260 (16%) receiving laboratory monitoring had a new serious adverse event, with anaemia being the most common (76 vs 61 cases).
President of the Southern Africa HIV Clinicians Society Dr Francois Venter said the trial came at exactly the right time, as funding restrictions start to threaten treatment programmes. ‘We need to critically look at everything we do, so as to ensure maximum access,’ he said.
Venter expressed one relative concern regarding this study ‘ ‘it was very well done, but used highly trained health care workers. It could be argued that in a less well monitored environment, we actually need lab monitoring to catch the patients who get missed by the clinicians.’
AIDS advocate Gregg Gonsalves said the DART study confirmed that antiretroviral therapy in Africa can be delivered effectively without high tech laboratory monitoring.
‘At a time when President Obama and other world leaders are considering cutting back on their commitment to AIDS treatment in the developing world, the DART study reminds us that ART can be delivered successfully in Africa and saves lives – only the lack of political will stands between life and death for millions of Africans,’ he said.
The authors confirmed that the results clearly showed that first-line ART can be delivered safely without routine biochemistry and haematology monitoring for toxic effects, but that routine CD4-cell count monitoring has a small but significant benefit in terms of disease progression and mortality, probably owing to slightly earlier switching to second-line ART.
‘DART results have major implications for ART programmes in Africa at a time when there is uncertainty about long-term funding and sustainability and when most people still cannot access treatment. We have shown that routine laboratory monitoring for toxic effects in HIV patients receiving ART has no benefit. ART can be delivered safely with good quality clinical care, allowing treatment delivery to be decentralised,’ they said.
They concluded that small differences in disease progression suggest a role for CD4-cell testing from the second year on ART to guide the switch to second-line ART and should encourage accelerated development of simpler, cheaper, point-of-care CD4 tests.
Laboratories will remain important for assessment of eligibility for ART, in terms of CD4-cell count and contraindications for specific drugs, and for diagnosis and management of opportunistic infections and clinical toxicity.
With less need to provide routine monitoring, particularly for toxicity, funding can be focused on drug procurement, strengthening of diagnostic laboratory services, and training and supervision for health-care workers to foster quality clinical monitoring, to support scale-up of ART rollout to rural Africa where 60% of the HIV-infected population live.