Optimizing infant HIV diagnosis with additional screening at immunization clinics in three sub-Saharan African settings: a cost-effectiveness analysis

Abstract

Introduction: Uptake of early infant HIV diagnosis (EID) varies widely across sub-Saharan African settings. We evaluated the potential clinical impact and cost-effectiveness of universal maternal HIV screening at infant immunization visits, with referral to EID and maternal antiretroviral therapy (ART) initiation.

Methods: Using the CEPAC-Pediatric model, we compared two strategies for infants born in 2017 in Côte d'Ivoire (CI), South Africa (SA), and Zimbabwe: (1) existing EID programmes offering six-week nucleic acid testing (NAT) for infants with known HIV exposure (EID), and (2) EID plus universal maternal HIV screening at six-week infant immunization visits, leading to referral for infant NAT and maternal ART initiation (screen-and-test). Model inputs included published Ivoirian/South African/Zimbabwean data: maternal HIV prevalence (4.8/30.8/16.1%), current uptake of EID (40/95/65%) and six-week immunization attendance (99/74/94%). Referral rates for infant NAT and maternal ART initiation after screen-and-test were 80%. Costs included NAT ($24/infant), maternal screening ($10/mother-infant pair), ART ($5 to 31/month) and HIV care ($15 to 190/month). Model outcomes included mother-to-child transmission of HIV (MTCT) among HIV-exposed infants, and life expectancy (LE) and mean lifetime per-person costs for children with HIV (CWH) and all children born in 2017. We calculated incremental cost-effectiveness ratios (ICERs) using discounted (3%/year) lifetime costs and LE for all children. We considered two cost-effectiveness thresholds in each country: (1) the per-capita GDP ($1720/6380/2150) per year-of-life saved (YLS), and (2) the CEPAC-generated ICER of offering 2 versus 1 lifetime ART regimens (e.g. offering second-line ART; $520/500/580/YLS).

Results: With EID, projected six-week MTCT was 9.3% (CI), 4.2% (SA) and 5.2% (Zimbabwe). Screen-and-test decreased total MTCT by 0.2% to 0.5%, improved LE by 2.0 to 3.5 years for CWH and 0.03 to 0.07 years for all children, and increased discounted costs by $17 to 22/child (all children). The ICER of screen-and-test compared to EID was $1340/YLS (CI), $650/YLS (SA) and $670/YLS (Zimbabwe), below the per-capita GDP but above the ICER of 2 versus 1 lifetime ART regimens in all countries.

Conclusions: Universal maternal HIV screening at immunization visits with referral to EID and maternal ART initiation may reduce MTCT, improve paediatric LE, and be of comparable value to current HIV-related interventions in high maternal HIV prevalence settings like SA and Zimbabwe.

Keywords: Early infant diagnosis; HIV; HIV-exposed infants; immunization; paediatric HIV testing; prevention of mother-to-child HIV transmission.

Figure 1

Mechanisms of HIV detection among children ever infected with HIV at 1 year from birth in the screen‐and‐test strategy in Côte d’Ivoire. Bar graph representing mechanisms of HIV detection among simulated infants with the proposed screen‐and‐test strategy. The left bar represents the proportions alive and dead at 1 year from birth of all infants who had acquired HIV by that time; results are reported separately for infants who acquired HIV during the IU/IP (dark green) vs. PP (light green) periods. The bottom right (IU/IP) and top right (PP) bars provide further details about the proportion of infants alive at 12 months of age who are undetected or were detected by an OI, existing EID programmes, or the screen‐and‐test programme. Similar results were observed in South Africa and Zimbabwe (see Appendix Table S3). Abbreviations: EID, early infant diagnosis; IP, intrapartum; IU, intrauterine; OI, opportunistic infection; PP, postpartum.

Figure 2

Univariate sensitivity analysis examining the impact of key input parameters on the cost‐effectiveness of screen‐and‐test compared to EID in (A) Côte d’Ivoire, (B) South Africa and (C) Zimbabwe. Univariate sensitivity analyses describing the impact of key input parameters on cost‐effectiveness results. The horizontal axis shows the incremental cost‐effectiveness ratio of screen‐and‐test compared to EID. The range through which each parameter is varied is shown in parentheses (value leading to the lowest shown ICER first, followed by value leading to the greatest shown ICER, with base‐case value after the semicolon). The length of each bar reflects the degree to which cost‐effectiveness is sensitive to variations in each parameter, with longest bars (greatest impact) at the top. Dark blue bars represent parameters for which published data ranges were available (data‐informed parameters, evaluated to understand the impact of parameter uncertainty on model outcomes); grey bars represent parameters for which no detailed data ranges were available (and thus wide ranges were evaluated to identify thresholds at which policy conclusions would change). The cost‐effectiveness criteria used are as follows: (1) the ICER of 2 versus 1 lifetime ART regimens (Côte d’Ivoire: $520/YLS; South Africa: $500/YLS; Zimbabwe: $580/YLS), and 2) the per‐capita GDP/YLS (Côte d’Ivoire: $1720/YLS; South Africa: $6380/YLS; Zimbabwe: $2150/YLS). Maternal HIV prevalence and incidence were varied together, holding the ratio of incidence to prevalence constant (0.008), to capture plausible variation in severity of the HIV epidemic. Several parameters did not influence the ICER of screen‐and‐test versus EID and thus are not shown here: In Côte d’Ivoire, the ICER of screen‐and‐test compared to EID was not sensitive to 3 parameters varied through data‐informed ranges (maternal HIV incidence [when varied alone], immunization coverage and the cost of infant NAT) and 1 parameter varied through wide ranges (acute OI care costs). In South Africa, the ICER of screen‐and‐test compared to EID was not sensitive to five parameters varied through data‐informed ranges (maternal HIV prevalence, maternal HIV incidence [when varied alone], immunization coverage, maternal ART coverage during pregnancy/breastfeeding and the cost of infant NAT) and 2 parameters varied through wide ranges (infant linkage to care after EID and acute OI care costs). In Zimbabwe, the ICER of screen‐and‐test compared to EID was not sensitive to 3 parameters varied through data‐informed ranges (maternal HIV incidence [when varied alone], maternal ART coverage during pregnancy/breastfeeding and the cost of infant NAT) and 1 parameter varied through wide ranges (infant linkage to care after detection by OI). All other input parameters shown in Table 1 were not influential on the ICER of screen‐and‐test versus EID in any country setting. Abbreviations: ART, antiretroviral therapy; EID, early infant diagnosis; ICER, incremental cost‐effectiveness ratio; NAT, nucleic test; YLS, year‐of‐life saved

Figure 3

Multivariate analyses examining the impact of simultaneously varying maternal HIV prevalence and maternal knowledge of HIV status (top three panels), and infant linkage to NAT after maternal screening and the cost of the screening programme (bottom three panels) in Côte d’Ivoire, South Africa and Zimbabwe. Multivariate sensitivity analyses describing the joint impacts of maternal HIV prevalence and maternal awareness of HIV status (top three panels), and infant linkage to NAT after screen‐and‐test and the cost of the screening programme (bottom three panels) on cost‐effectiveness results. The cost‐effectiveness criteria used are as follows: (1) the ICER of 2 versus 1 lifetime ART regimens (Côte d’Ivoire: $520/YLS; South Africa: $500/YLS; Zimbabwe: $580/YLS), and 2) the per‐capita GDP/YLS (Côte d’Ivoire: $1720/YLS; South Africa: $6380/YLS; Zimbabwe: $2150/YLS). Red portions of the figure represent conditions where screen‐and‐test is not cost‐effective by either cost‐effectiveness criteria (the ICER of screen‐and‐test compared to EID is greater than the ICER of 2 versus 1 lifetime ART regimens and greater than the per‐capita GDP/YLS). Light green shading represents an ICER greater than the ICER of 2 versus 1 lifetime ART regimens but less than the per‐capita GDP/YLS. Dark green shading represents an ICER less than the ICER of 2 versus 1 lifetime ART regimens and less than the per‐capita GDP/YLS. Abbreviations: ART, antiretroviral therapy; ICER, incremental cost‐effectiveness ratio; NAT, nucleic acid test.