Cost-effectiveness of broadly neutralizing antibodies for infant HIV prophylaxis in settings with high HIV burdens: a simulation modeling study

Abstract

Introduction: Approximately 130 000 infants acquire HIV annually despite global maternal antiretroviral therapy scale-up. We evaluated the potential clinical impact and cost-effectiveness of offering long-acting, anti-HIV broadly neutralizing antibody (bNAb) prophylaxis to infants in three distinct settings.

Methods: We simulated infants in Côte d'Ivoire, South Africa, and Zimbabwe using the Cost-Effectiveness of Preventing AIDS Complications-Pediatric (CEPAC-P) model. We modeled strategies offering a three-bNAb combination in addition to WHO-recommended standard-of-care oral prophylaxis to infants: a) with known, WHO-defined high-risk HIV exposure at birth (HR-HIVE); b) with known HIV exposure at birth (HIVE); or c) with or without known HIV exposure (ALL). Modeled infants received 1-dose, 2-doses, or Extended (every 3 months through 18 months) bNAb dosing. Base case model inputs included 70% bNAb efficacy (sensitivity analysis range: 10-100%), 3-month efficacy duration/dosing interval (1-6 months), and $20/dose cost ($5-$100/dose). Outcomes included pediatric HIV infections, life expectancy, lifetime HIV-related costs, and incremental cost-effectiveness ratios (ICERs, in US$/year-of-life-saved [YLS], assuming a ≤50% GDP per capita cost-effectiveness threshold).

Results: The base case model projects that bNAb strategies targeting HIVE and ALL infants would prevent 7-26% and 10-42% additional pediatric HIV infections, respectively, compared to standard-of-care alone, ranging by dosing approach. HIVE-Extended would be cost-effective (cost-saving compared to standard-of-care) in Côte d'Ivoire and Zimbabwe; ALL-Extended would be cost-effective in South Africa (ICER: $882/YLS). BNAb strategies targeting HR-HIVE infants would result in greater lifetime costs and smaller life expectancy gains than HIVE-Extended. Throughout most bNAb efficacies and costs evaluated in sensitivity analyses, targeting HIVE infants would be cost-effective in Côte d'Ivoire and Zimbabwe, and targeting ALL infants would be cost-effective in South Africa.

Discussion: Adding long-acting bNAbs to current standard-of-care prophylaxis would be cost-effective, assuming plausible efficacies and costs. The cost-effective target population would vary by setting, largely driven by maternal antenatal HIV prevalence and postpartum incidence.

Figure 1.. Base case number of model-projected HIV infections prevented by bNAb strategies, by country

The number of model-estimated pediatric HIV infections (i.e., before 36 months) prevented by each broadly neutralizing antibody (bNAb) strategy, compared to the standard-of-care alone, is presented for Côte d’Ivoire (Panel A), South Africa (Panel B), and Zimbabwe (Panel C). The axes on each panel are different due to the different number of projected infections in the standard-of-care alone. Abbreviations: HIVE, bNAb strategy targeting infants with known HIV exposure; ALL, bNAb strategy targeting all infants; mo., month.

Figure 2.. Breakdown of base case model-projected postnatal vertical HIV transmissions occurring in each exposure group, by country

The number of postnatal pediatric HIV infections (i.e., before 36 months) occurring in each of four exposure groups assessed at birth (i.e., among infants who are initially unexposed, infants who are unrecognized to be HIV-exposed, infants with known low-risk exposure, or infants with known high-risk exposure) is presented for Côte d’Ivoire (Panel A), South Africa (Panel B), and Zimbabwe (Panel C). The “Hybrid” strategy (i.e., ALL–1-dose plus HIVE–Extended) offers one dose of broadly neutralizing antibodies (bNAbs) to all infants with or without HIV exposure, and an additional bNAbs dose every three months to infants with known HIV exposure at birth for up to 18 months while breastfeeding. The estimated number of infants at risk of HIV acquisition in each exposure group varies by country. In Côte d’Ivoire, an estimated 6500 infants have known, high-risk HIV exposure at birth; 14 700 infants have known, low-risk HIV exposure at birth; 1100 infants have unrecognized HIV exposure at birth; and 400 infants are first exposed postnatally. In South Africa, an estimated 65 600 infants have known, high-risk HIV exposure at birth; 294 500 infants have known, low-risk HIV exposure at birth; 18 400 infants have unrecognized HIV exposure at birth; and 9700 infants are first exposed postnatally. In Zimbabwe, an estimated 11 500 infants have known, high-risk HIV exposure at birth; 35 400 infants have known, low-risk HIV exposure at birth; 3600 infants have unrecognized HIV exposure at birth; and 2100 infants are first exposed postnatally. Abbreviations: HR-HIVE, bNAb strategy targeting infants with known, high-risk HIV exposure; HIVE, bNAb strategy targeting infants with known HIV exposure; ALL, bNAb strategy targeting all infants; SOC, standard-of-care; 1d, one dose; 2d, two dose; Ext, extended; mo., month.

Figure 3.. Cost-effectiveness results of a three-way sensitivity analysis assessing bNAb efficacy, cost, and maternal HIV prevalence/incidence, by country

We conducted a three-way sensitivity analysis on the impact of bNAb cost per dose (vertical axis), efficacy per dose (horizontal axis), and maternal HIV prevalence (left to right panels) on the cost-effective bNAb strategy in the three countries examined: Côte d’Ivoire (Panels A-C), South Africa (Panels D-F), and Zimbabwe (Panels G-I). To simulate low (left-most panels) and high (right-most panels) maternal prevalence scenarios, we used the lowest and highest subnational maternal prevalence point estimates reported in survey data as inputs.^,, Maternal prevalence at the time of delivery is inclusive of chronic HIV infection and incident infection during pregnancy. Postpartum maternal HIV incidence was also decreased (Côte d’Ivoire: 0.001%/month, South Africa: 0.107%/month, Zimbabwe: 0.022%/month) or increased (Côte d’Ivoire: 0.005%/month, South Africa: 0.331%/month, Zimbabwe: 0.116%/month) proportional to the change in prevalence. BNAb strategies targeting only high-risk infants known to be HIV-exposed at birth (HR-HIVE) are depicted in shades of green. Strategies targeting all infants known to be HIV-exposed (HIVE) are depicted in shades of blue, and strategies targeting all infants irrespective of HIV exposure (ALL) are depicted in shades of purple. The hybrid strategy offering one dose of bNAbs at birth to all infants irrespective of HIV exposure and extended bNAb doses to infants known to be HIV-exposed (Hybrid) is depicted in red. Eligible infants would receive either one dose, two doses, or a dose of bNAbs every three months while breastfeeding for up to 18 months (i.e., extended dosing). The cost-effective bNAb strategy was defined as per the methods. The white “X” in each panel reflects the base case assumptions of 70% bNAb efficacy at a cost of $20/dose. Abbreviations: bNAb, broadly neutralizing antibody; mo., month.