Utility of routine viral load, CD4 cell count, and clinical monitoring among adults with HIV receiving antiretroviral therapy in Uganda: randomised trial

Abstract

Objective: To evaluate the use of routine laboratory monitoring in terms of clinical outcomes among patients receiving antiretroviral therapy (ART) in Uganda.

Design: Randomised clinical trial

Setting: A home based ART programme in rural Uganda.

Participants: All participants were people with HIV who were members of the AIDS Support Organisation. Participants had CD4 cell counts <250 cells × 10(6)/L or World Health Organization stage 3 or 4 disease.

Interventions: Participants were randomised to one of three different monitoring arms: a viral load arm (clinical monitoring, quarterly CD4 counts, and viral load measurements), CD4 arm (clinical monitoring and CD4 counts), or clinical arm (clinical monitoring alone).

Main outcome measures: Serious morbidity (newly diagnosed AIDS defining illness) and mortality.

Results: 1094 participants started ART; median CD4 count at baseline was 129 cells × 10(6)/L. Median follow-up was three years. In total, 126 participants died (12%), 148 (14%) experienced new AIDS defining illnesses, and 61(6%) experienced virological failure, defined as two consecutive viral loads >500 copies/mL occurring more than three months after the start of ART. After adjustment for age, sex, baseline CD4 count, viral load, and body mass index, the rate of new AIDS defining events or death was higher in the clinical arm than the viral load arm (adjusted hazard ratio 1.83, P = 0.002) or the CD4 arm (1.49, P = 0.032). There was no significant difference between the CD4 arm and the viral load arm (1.23, P = 0.31).

Conclusion: In patients receiving ART for HIV infection in Uganda, routine laboratory monitoring is associated with improved health and survival compared with clinical monitoring alone. Trial registration Clinical Trials NCT00119093.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: JM, JPE, WW, RD, RB, FK, RD, PS, LNA, JT, DMM had support from the US Center for Disease Control for the submitted work. AC received no direct support for this study; DMM also received support from the Canadian Institutes for Health Research through a New Investigator Award; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Ethical approval: The studies were approved by the Institutional Review Boards of the Centers for Disease Control and Prevention and the Uganda Virus Research Institute and informed consent was given by all patients.

Figures

Fig 1 Trial profile of participants with HIV enrolled and followed up in study monitoring efficacy of ART, Tororo and Busia Districts, Uganda, 2003-7

Fig 2 Time to first event of severe morbidity or mortality, intention to treat analysis, Tororo and Busia Districts, Uganda, 2003-7 (log rank P=0.067). P=0.02 for viral load v clinical, P=0.22 for CD4 v clinical, P=0.26 for viral load v CD4

Fig 3 Time to first severe morbidity event or death, per protocol analysis excluding first 90 days of ART, Tororo and Busia Districts, Uganda, 2003-7 (log rank P<0.009). P=0.004 for viral load v clinical, P=0.034 for CD4 v clinical, P=0.46 for viral load v CD4