Laboratory monitoring to guide switching antiretroviral therapy in resource-limited settings: clinical benefits and cost-effectiveness

Abstract

Background: As second-line antiretroviral therapy (ART) availability increases in resource-limited settings, questions about the value of laboratory monitoring remain. We assessed the outcomes and cost-effectiveness (CE) of laboratory monitoring to guide switching ART.

Methods: We used a computer model to project life expectancy and costs of different strategies to guide ART switching in patients in Côte d'Ivoire. Strategies included clinical assessment, CD4 count, and HIV RNA testing. Data were from clinical trials and cohort studies from Côte d'Ivoire and the literature. Outcomes were compared using the incremental CE ratio. We conducted multiple sensitivity analyses to assess uncertainty in model parameters.

Results: Compared with first-line ART only, second-line ART increased life expectancy by 24% with clinical monitoring only, 46% with CD4 monitoring, and 61% with HIV RNA monitoring. The incremental CE ratio of switching based on clinical monitoring was $1670 per year of life gained (YLS) compared with first-line ART only; biannual CD4 monitoring was $2120 per YLS. The CE ratio of biannual HIV RNA testing ranged from $2920 ($87/test) to $1990 per YLS ($25/test). If second-line ART costs were reduced, the CE of HIV RNA monitoring improved.

Conclusions: In resource-limited settings, CD4 count and HIV RNA monitoring to guide switching to second-line ART improve survival and, under most conditions, are cost-effective.

Figure A1. Percent time on antiretroviral therapy, by virologic suppression status and type of monitoring strategy

This figure depicts the percent of undiscounted life expectancy on 1^st- and 2^nd-line ART, by virologic suppression status and type of monitoring. Each bar reflects a representative clinical (failure criterion: 1 WHO stage III-IV event, excluding tuberculosis and invasive bacterial diseases), immunologic (failure criterion: 50% decrease in peak on-treatment CD4), or virologic (failure criterion: 1 log₁₀ increase in or return to pre-treatment HIV RNA level, immediate switch) monitoring strategy. Time on suppressed and virologically failed 1^st-line ART is shown dark red ( ) and dark purple ( ), respectively. Time on suppressed and virologically failed 2^nd-line ART is shown in lighter red ( ) and lighter purple ( ), respectively. Detecting ART failure earlier — as occurs when using HIV RNA monitoring — resulted in a shorter duration on virologically failed 1^st-line ART and longer total duration on 2^nd-line ART. ART: antiretroviral therapy.

Figure A2. 20-year survival, by type of monitoring strategy

This figure depicts time (x-axis) and survivorship (y-axis) for a treatment-eligible cohort entering care with mean CD4 140 cells/μL (standard deviation 116 cells/μL) for patients relying on clinical- (small dashed line), CD4- (solid line), or HIV RNA- (large dashed line) based switching strategies. Median survivals, indicated by the dotted line, were 12.79, 16.13, and 18.96 years, respectively. At approximately 2 years, the proportion of the initial cohort surviving and receiving HIV RNA monitoring began to diverge from the proportion of the cohort surviving and receiving clinical and CD4 count monitoring. By 5 years, the proportion of the initial cohort surviving and receiving CD4 count monitoring diverged from the proportion of the initial cohort surviving and receiving clinical monitoring.

Figure 1

Sensitivity analysis: incremental cost-effectiveness of virologic monitoring. This figure depicts the results of sensitivity analyses on the incremental cost-effectiveness of virologic monitoring with HIV RNA test costs of $50 (Upper Panel) and $87 (Lower Panel). The horizontal axis shows variations in the incremental cost-effectiveness ratio (US$ per YLS) due to changes in values of select model variables listed on the vertical axis. Late failure refers to the monthly risk of virological failure for virologically suppressed patients. “Resistance penalty” refers to the decrease in 2^nd-line ART efficacy due to time on virologically failed 1^st-line ART (see Methods for details). Values in parentheses specify the upper and lower bounds assessed for each variable. The vertical broken line indicates the incremental cost-effectiveness ratio of virologic monitoring at an HIV RNA test cost of either $50 (upper) or $87 (lower). ICER: incremental cost-effectiveness ratio; ART: antiretroviral therapy; YLS: year of life gained.

Figure 1

Sensitivity analysis: incremental cost-effectiveness of virologic monitoring. This figure depicts the results of sensitivity analyses on the incremental cost-effectiveness of virologic monitoring with HIV RNA test costs of $50 (Upper Panel) and $87 (Lower Panel). The horizontal axis shows variations in the incremental cost-effectiveness ratio (US$ per YLS) due to changes in values of select model variables listed on the vertical axis. Late failure refers to the monthly risk of virological failure for virologically suppressed patients. “Resistance penalty” refers to the decrease in 2^nd-line ART efficacy due to time on virologically failed 1^st-line ART (see Methods for details). Values in parentheses specify the upper and lower bounds assessed for each variable. The vertical broken line indicates the incremental cost-effectiveness ratio of virologic monitoring at an HIV RNA test cost of either $50 (upper) or $87 (lower). ICER: incremental cost-effectiveness ratio; ART: antiretroviral therapy; YLS: year of life gained.

Figure 2

Cost-effectiveness of switching to 2^nd-line antiretroviral therapy: the efficient frontier. This figure shows 4 strategies considered to be efficient, including Clinical A (clinical monitoring with a failure criterion of WHO Stage III-IV event (excluding tuberculosis and invasive bacterial diseases)), CD4 count (immunologic monitoring with 1^st-line ART failure criteria based on CD4 declines of 50% or 25% from peak on-treatment CD4 count), and HIV RNA test (virologic monitoring with failure criteria based on a log₁₀ increase in or return to pre-treatment HIV RNA). All other strategies shown are more costly and less effective (i.e., strongly dominated), or more costly and less cost-effective (i.e., weakly dominated). Where applicable, an HIV RNA test cost of $87 was assumed.