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A cluster randomized trial of routine HIV-1 viral load monitoring in Zambia: study design, implementation, and baseline cohort characteristics.

Koethe JR, Westfall AO, Luhanga DK, Clark GM, Goldman JD, Mulenga PL, Cantrell RA, Chi BH, Zulu I, Saag MS, Stringer JS - PLoS ONE (2010)

Bottom Line: The benefit of routine HIV-1 viral load (VL) monitoring of patients on antiretroviral therapy (ART) in resource-constrained settings is uncertain because of the high costs associated with the test and the limited treatment options.The study was powered to detect a 36% reduction in mortality at 18 months.Measured baseline characteristics did not differ significantly between the study arms.

View Article: PubMed Central - PubMed

Affiliation: Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.

ABSTRACT

Background: The benefit of routine HIV-1 viral load (VL) monitoring of patients on antiretroviral therapy (ART) in resource-constrained settings is uncertain because of the high costs associated with the test and the limited treatment options. We designed a cluster randomized controlled trial to compare the use of routine VL testing at ART-initiation and at 3, 6, 12, and 18 months, versus our local standard of care (which uses immunological and clinical criteria to diagnose treatment failure, with discretionary VL testing when the two do not agree).

Methodology: Dedicated study personnel were integrated into public-sector ART clinics. We collected participant information in a dedicated research database. Twelve ART clinics in Lusaka, Zambia constituted the units of randomization. Study clinics were stratified into pairs according to matching criteria (historical mortality rate, size, and duration of operation) to limit the effect of clustering, and independently randomized to the intervention and control arms. The study was powered to detect a 36% reduction in mortality at 18 months.

Principal findings: From December 2006 to May 2008, we completed enrollment of 1973 participants. Measured baseline characteristics did not differ significantly between the study arms. Enrollment was staggered by clinic pair and truncated at two matched sites.

Conclusions: A large clinical trial of routing VL monitoring was successfully implemented in a dynamic and rapidly growing national ART program. Close collaboration with local health authorities and adequate reserve staff were critical to success. Randomized controlled trials such as this will likely prove valuable in determining long-term outcomes in resource-constrained settings.

Trial registration: Clinicaltrials.gov NCT00929604.

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Related in: MedlinePlus

Detectable hazard ratio as a consequence of utilizing routine HIV-1 viral load monitoring at varying between-clinic coefficients of variation.Calculation assumes a historical 18 month post-ART mortality rate of 15.6 per 100 years (140 patients remaining per clinic).
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pone-0009680-g002: Detectable hazard ratio as a consequence of utilizing routine HIV-1 viral load monitoring at varying between-clinic coefficients of variation.Calculation assumes a historical 18 month post-ART mortality rate of 15.6 per 100 years (140 patients remaining per clinic).

Mentions: The study was powered to detect a hazard ratio of 0.64 or lower as a consequence of utilizing routine VL monitoring in clinical care, which represented a 36% reduction in mortality (15.6 per 100 person-years versus 10.0 per 100 person years). Matching clinics will permit the use of a matched k in future analyses, which should be lower than the unmatched k and may improve study power. Using our estimated unmatched k (0.14) as a conservative estimate of the matched k, 1680 participants (140 per clinic; alive or deceased) will need to remain in the study after 18 months of follow-up to maintain the sample size assumed in the power calculations. [20] Figure 2 shows the detectable hazard ratio (alpha of 0.05 and beta of 0.20) at different coefficients of variation.


A cluster randomized trial of routine HIV-1 viral load monitoring in Zambia: study design, implementation, and baseline cohort characteristics.

Koethe JR, Westfall AO, Luhanga DK, Clark GM, Goldman JD, Mulenga PL, Cantrell RA, Chi BH, Zulu I, Saag MS, Stringer JS - PLoS ONE (2010)

Detectable hazard ratio as a consequence of utilizing routine HIV-1 viral load monitoring at varying between-clinic coefficients of variation.Calculation assumes a historical 18 month post-ART mortality rate of 15.6 per 100 years (140 patients remaining per clinic).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2837376&req=5

pone-0009680-g002: Detectable hazard ratio as a consequence of utilizing routine HIV-1 viral load monitoring at varying between-clinic coefficients of variation.Calculation assumes a historical 18 month post-ART mortality rate of 15.6 per 100 years (140 patients remaining per clinic).
Mentions: The study was powered to detect a hazard ratio of 0.64 or lower as a consequence of utilizing routine VL monitoring in clinical care, which represented a 36% reduction in mortality (15.6 per 100 person-years versus 10.0 per 100 person years). Matching clinics will permit the use of a matched k in future analyses, which should be lower than the unmatched k and may improve study power. Using our estimated unmatched k (0.14) as a conservative estimate of the matched k, 1680 participants (140 per clinic; alive or deceased) will need to remain in the study after 18 months of follow-up to maintain the sample size assumed in the power calculations. [20] Figure 2 shows the detectable hazard ratio (alpha of 0.05 and beta of 0.20) at different coefficients of variation.

Bottom Line: The benefit of routine HIV-1 viral load (VL) monitoring of patients on antiretroviral therapy (ART) in resource-constrained settings is uncertain because of the high costs associated with the test and the limited treatment options.The study was powered to detect a 36% reduction in mortality at 18 months.Measured baseline characteristics did not differ significantly between the study arms.

View Article: PubMed Central - PubMed

Affiliation: Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.

ABSTRACT

Background: The benefit of routine HIV-1 viral load (VL) monitoring of patients on antiretroviral therapy (ART) in resource-constrained settings is uncertain because of the high costs associated with the test and the limited treatment options. We designed a cluster randomized controlled trial to compare the use of routine VL testing at ART-initiation and at 3, 6, 12, and 18 months, versus our local standard of care (which uses immunological and clinical criteria to diagnose treatment failure, with discretionary VL testing when the two do not agree).

Methodology: Dedicated study personnel were integrated into public-sector ART clinics. We collected participant information in a dedicated research database. Twelve ART clinics in Lusaka, Zambia constituted the units of randomization. Study clinics were stratified into pairs according to matching criteria (historical mortality rate, size, and duration of operation) to limit the effect of clustering, and independently randomized to the intervention and control arms. The study was powered to detect a 36% reduction in mortality at 18 months.

Principal findings: From December 2006 to May 2008, we completed enrollment of 1973 participants. Measured baseline characteristics did not differ significantly between the study arms. Enrollment was staggered by clinic pair and truncated at two matched sites.

Conclusions: A large clinical trial of routing VL monitoring was successfully implemented in a dynamic and rapidly growing national ART program. Close collaboration with local health authorities and adequate reserve staff were critical to success. Randomized controlled trials such as this will likely prove valuable in determining long-term outcomes in resource-constrained settings.

Trial registration: Clinicaltrials.gov NCT00929604.

Show MeSH
Related in: MedlinePlus