First-line antiretroviral therapy after single-dose nevirapine exposure in South Africa: a cost-effectiveness analysis of the OCTANE trial

Abstract

Background: The OCTANE trial reports superior outcomes of lopinavir/ritonavir vs. nevirapine-based antiretroviral therapy (ART) among women previously exposed to single-dose nevirapine to prevent mother-to-child HIV transmission. However, lopinavir/ritonavir is 12 times costlier than nevirapine.

Methods: We used a computer model, with OCTANE and local data, to simulate HIV-infected, single-dose nevirapine-exposed women in South Africa. Outcomes of three alternative ART sequences were projected: no ART (for comparison), first-line nevirapine, and first-line lopinavir/ritonavir. OCTANE data included mean age (31 years) and CD4 cell count (135/μl); median time since single-dose nevirapine (17 months); and 24-week viral suppression efficacy for first-line ART (nevirapine: 85%, lopinavir/ritonavir: 97%). Outcomes included life expectancy, per-person costs (2008 US$), and incremental cost-effectiveness ratios.

Results: With no ART, projected life expectancy was 1.6 years and per-person cost was $2980. First-line nevirapine increased life expectancy (15.2 years) and cost ($13 990; cost-effectiveness ratio: $810/year of life saved versus no ART). First-line lopinavir/ritonavir further increased life expectancy to 16.3 years and cost to $15 630 (cost-effectiveness ratio: $1520/year of life saved versus first-line nevirapine). First-line lopinavir/ritonavir cost-effectiveness was sensitive to prevalence of nevirapine-resistant virus at ART initiation, time from single-dose nevirapine exposure to ART initiation (6-12, 12-24, or >24 months), second-line ART efficacies, and outcomes after 24 weeks on ART.

Conclusions: First-line lopinavir/ritonavir-based ART is very cost-effective in single-dose nevirapine-exposed, South African women similar to OCTANE participants. Lopinavir/ritonavir should be initiated in women with known nevirapine resistance or single-dose nevirapine exposure less than 12 months prior, or in whom such information is unknown.

Figure 1

NVP: nevirapine; ART: antiretroviral therapy; LPV/r: lopinavir/ritonavir; ICER: incremental cost-effectiveness ratio; YLS: year of life saved A “tornado diagram” summarizes the results of a series of 1-way sensitivity analyses. Key model parameters are listed on the vertical axis. For each parameter, the value used in the base case analysis and the range examined in sensitivity analyses are listed in parentheses. The horizontal axis represents cost-effectiveness ratios for 1^st-line LPV/r compared to 1^st-line NVP. Each horizontal bar represents the range of cost-effectiveness ratios produced by varying model parameter across the ranges shown. The solid vertical line denotes the base case cost-effectiveness ratio estimate ($1,520/YLS, and the dashed vertical line denotes the cost-effectiveness ratio of $5,700 (2008 South African GDP) per YLS. Numbers in parentheses above each horizontal bar indicate the threshold value of each parameter at which the cost-effectiveness ratio for 1^st-line LPV/r compared to nevirapine becomes <$5,700/YLS. The horizontal axis should be understood to extend to the right beyond $60,000/YLS and to include instances when 1^st-line LPV/r costs more and dominates 1^st-line NVP (as is the case when 2^nd-line LPV/r efficacy is ≥90%). Bars abutting the far left margin indicate situations in which 1^st-line LPV/r costs less and confers more life-years than 1^st-line NVP, or in which 1^st-line NVP is dominated (see Table 4, footnote b).

Figure 2

ICER: incremental cost-effectiveness ratio; LPV/r: lopinavir/ritonavir; NVP: nevirapine; YLS: year of life saved; GDP: gross domestic product; NNRTI: non-nucleoside reverse transcriptase inhibitor; ART: antiretroviral therapy. Two-way sensitivity analyses depicting the simultaneous impact of the prevalence of NNRTI resistance at baseline and the efficacy of the 2^nd-line ART in suppressing HIV RNA to <400 copies/ml at 24 weeks. In both panels, the vertical axis indicates the cost-effectiveness ratio for 1^st-line LPV/r compared to 1^st-line NVP in $/YLS. The vertical axis should be understood to extend beyond the $18,000/YLS mark, to include situations in which 1^st-line LPV/r is “dominated” by 1^st-line NVP. The shaded regions indicate a cost-effectiveness ratio of <$5,700/YLS. In panel A, the horizontal axis represents varying values for 2^nd-line NVP efficacy. The green line indicates the OCTANE cohort in whom no NNRTI resistance was detected by standard genotypic resistance testing at the time of ART initiation. In this group, 2^nd-line NVP efficacy must be ≥44% (square) for the 1^st-line LPV/r cost-effectiveness ratio to fall below $5,700. The blue line indicates the base case scenario for the entire OCTANE cohort, in whom the prevalence of NNRTI resistance at baseline was 14%. For this group, 2^nd-line NVP efficacy must be ≥13% (circle) for the 1^st-line LPV/r cost-effectiveness ratio to fall below $5,700. The purple line indicates the OCTANE cohort in whom NNRTI resistance was detected at baseline. For this group, 1^st-line LPV/r is economically preferred to 1^st-line NVP at all values of 2^nd-line NVP efficacy, due to “extended dominance” (purple line). The cost-effectiveness ratios of LPV/r compared to no antiretroviral therapy are displayed in the Figure. In panel B, the horizontal axis represents values for 2^nd-line LPV/r efficacy. In the OCTANE cohort in whom no baseline NNRTI resistance was detected (green line) 2^nd-line LPV/r efficacy must be ≤73% (square) for the 1^st-line LPV/r cost-effectiveness ratio to fall below $5,700. In the entire OCTANE cohort (14% baseline resistance, blue line), 2^nd-line LPV/r efficacy must be ≤87% (circle) for the 1^st-line LPV/r cost-effectiveness ratio to fall below $5,700. For the group in whom NNRTI resistance was detected at baseline (purple line), 1^st-line LPV/r is again economically preferred to 1^st-line NVP at all values of 2^nd-line LPV/r efficacy, due to “extended dominance” (purple line). The cost-effectiveness ratio of LPV/r compared to no ART are displayed in the Figure.

Figure 2

ICER: incremental cost-effectiveness ratio; LPV/r: lopinavir/ritonavir; NVP: nevirapine; YLS: year of life saved; GDP: gross domestic product; NNRTI: non-nucleoside reverse transcriptase inhibitor; ART: antiretroviral therapy. Two-way sensitivity analyses depicting the simultaneous impact of the prevalence of NNRTI resistance at baseline and the efficacy of the 2^nd-line ART in suppressing HIV RNA to <400 copies/ml at 24 weeks. In both panels, the vertical axis indicates the cost-effectiveness ratio for 1^st-line LPV/r compared to 1^st-line NVP in $/YLS. The vertical axis should be understood to extend beyond the $18,000/YLS mark, to include situations in which 1^st-line LPV/r is “dominated” by 1^st-line NVP. The shaded regions indicate a cost-effectiveness ratio of <$5,700/YLS. In panel A, the horizontal axis represents varying values for 2^nd-line NVP efficacy. The green line indicates the OCTANE cohort in whom no NNRTI resistance was detected by standard genotypic resistance testing at the time of ART initiation. In this group, 2^nd-line NVP efficacy must be ≥44% (square) for the 1^st-line LPV/r cost-effectiveness ratio to fall below $5,700. The blue line indicates the base case scenario for the entire OCTANE cohort, in whom the prevalence of NNRTI resistance at baseline was 14%. For this group, 2^nd-line NVP efficacy must be ≥13% (circle) for the 1^st-line LPV/r cost-effectiveness ratio to fall below $5,700. The purple line indicates the OCTANE cohort in whom NNRTI resistance was detected at baseline. For this group, 1^st-line LPV/r is economically preferred to 1^st-line NVP at all values of 2^nd-line NVP efficacy, due to “extended dominance” (purple line). The cost-effectiveness ratios of LPV/r compared to no antiretroviral therapy are displayed in the Figure. In panel B, the horizontal axis represents values for 2^nd-line LPV/r efficacy. In the OCTANE cohort in whom no baseline NNRTI resistance was detected (green line) 2^nd-line LPV/r efficacy must be ≤73% (square) for the 1^st-line LPV/r cost-effectiveness ratio to fall below $5,700. In the entire OCTANE cohort (14% baseline resistance, blue line), 2^nd-line LPV/r efficacy must be ≤87% (circle) for the 1^st-line LPV/r cost-effectiveness ratio to fall below $5,700. For the group in whom NNRTI resistance was detected at baseline (purple line), 1^st-line LPV/r is again economically preferred to 1^st-line NVP at all values of 2^nd-line LPV/r efficacy, due to “extended dominance” (purple line). The cost-effectiveness ratio of LPV/r compared to no ART are displayed in the Figure.