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Journal Article > ResearchFull Text

Monitoring of antiretroviral therapy and mortality in HIV programmes in Malawi, South Africa and Zambia: mathematical modelling study

PLOS One. 28 February 2013; Volume 8 (Issue 2); e57611.; DOI:10.1371/journal.pone.0057611
Estill J, Egger M, Johnson LF, Gsponer T, Wandeler G,  et al.
PLOS One. 28 February 2013; Volume 8 (Issue 2); e57611.; DOI:10.1371/journal.pone.0057611
OBJECTIVES
Mortality in patients starting antiretroviral therapy (ART) is higher in Malawi and Zambia than in South Africa. We examined whether different monitoring of ART (viral load [VL] in South Africa and CD4 count in Malawi and Zambia) could explain this mortality difference.

DESIGN
Mathematical modelling study based on data from ART programmes.

METHODS
We used a stochastic simulation model to study the effect of VL monitoring on mortality over 5 years. In baseline scenario A all parameters were identical between strategies except for more timely and complete detection of treatment failure with VL monitoring. Additional scenarios introduced delays in switching to second-line ART (scenario B) or higher virologic failure rates (due to worse adherence) when monitoring was based on CD4 counts only (scenario C). Results are presented as relative risks (RR) with 95% prediction intervals and percent of observed mortality difference explained.

RESULTS
RRs comparing VL with CD4 cell count monitoring were 0.94 (0.74-1.03) in scenario A, 0.94 (0.77-1.02) with delayed switching (scenario B) and 0.80 (0.44-1.07) when assuming a 3-times higher rate of failure (scenario C). The observed mortality at 3 years was 10.9% in Malawi and Zambia and 8.6% in South Africa (absolute difference 2.3%). The percentage of the mortality difference explained by VL monitoring ranged from 4% (scenario A) to 32% (scenarios B and C combined, assuming a 3-times higher failure rate). Eleven percent was explained by non-HIV related mortality.

CONCLUSIONS
VL monitoring reduces mortality moderately when assuming improved adherence and decreased failure rates.
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Journal Article > ResearchFull Text

Viral load versus CD4⁺ monitoring and 5-year outcomes of antiretroviral therapy in HIV-positive children in Southern Africa: a cohort-based modelling study

AIDS. 23 October 2014; Volume 28 (Issue 16); 2451-60.; DOI:10.1097/qad.0000000000000446
Salazar-Vizcaya L, Keiser O, Technau KG, Davies MA, Haas AD,  et al.
AIDS. 23 October 2014; Volume 28 (Issue 16); 2451-60.; DOI:10.1097/qad.0000000000000446
OBJECTIVES
Many paediatric antiretroviral therapy (ART) programmes in Southern Africa rely on CD4⁺ to monitor ART. We assessed the benefit of replacing CD4⁺ by viral load monitoring.

DESIGN
A mathematical modelling study.

METHODS
A simulation model of HIV progression over 5 years in children on ART, parameterized by data from seven South African cohorts. We simulated treatment programmes with 6-monthly CD4⁺ or 6- or 12-monthly viral load monitoring. We compared mortality, second-line ART use, immunological failure and time spent on failing ART. In further analyses, we varied the rate of virological failure, and assumed that the rate is higher with CD4⁺ than with viral load monitoring.

RESULTS
About 7% of children were predicted to die within 5 years, independent of the monitoring strategy. Compared with CD4⁺ monitoring, 12-monthly viral load monitoring reduced the 5-year risk of immunological failure from 1.6 to 1.0% and the mean time spent on failing ART from 6.6 to 3.6 months; 1% of children with CD4⁺ compared with 12% with viral load monitoring switched to second-line ART. Differences became larger when assuming higher rates of virological failure. When assuming higher virological failure rates with CD4⁺ than with viral load monitoring, up to 4.2% of children with CD4⁺ compared with 1.5% with viral load monitoring experienced immunological failure; the mean time spent on failing ART was 27.3 months with CD4⁺ monitoring and 6.0 months with viral load monitoring. Conclusion: Viral load monitoring did not affect 5-year mortality, but reduced time on failing ART, improved immunological response and increased switching to second-line ART.
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Journal Article > ResearchFull Text

Viral Load Monitoring of Antiretroviral Therapy, cohort viral load and HIV transmission in Southern Africa: A Mathematical Modelling Analysis

AIDS. 20 March 2012; Volume 26 (Issue 11); DOI:10.1097/QAD.0b013e3283536988
Estill J, Aubriere C, Egger M, Johnson LF, Wood R,  et al.
AIDS. 20 March 2012; Volume 26 (Issue 11); DOI:10.1097/QAD.0b013e3283536988
In low-income settings, treatment failure is often identified using CD4 cell count monitoring. Consequently, patients remain on a failing regimen, resulting in a higher risk of transmission. We investigated the benefit of routine viral load monitoring for reducing HIV transmission.More