Background

Since 2010, 1.4 million new HIV infections in children have been averted worldwide, while HIV mortality among children has halved [1, 2]. Despite this progress, 150,000 children were newly infected in 2019, falling short of the 2018 target to reduce new HIV infections in children to 40,000 [3]. In addition, HIV treatment coverage among children is significantly lower than among adults, likely due to higher levels of under-diagnosis [4]. Furthermore, many children present to clinical services and start antiretroviral therapy (ART) in older childhood and adolescence when they have developed advanced disease, with consequent poorer outcomes [5]. Notably, adolescents are the only age-group in whom HIV-related mortality has not declined [5,6,7,8]. HIV testing and counselling approaches aimed at the timely diagnosis and linkage to care of children and adolescents in high HIV prevalence settings are therefore urgently needed.

Index-linked testing refers to screening family, household or other contacts of a case for a disease. Index-linked HIV testing has been widely used to identify higher risk individuals, and thus a high-yielding strategy for HIV testing [9]. In sub-Saharan Africa children and adolescents living in households with known HIV-positive adults are more likely to be HIV-positive, and are often untested and untreated [9,10,11]. Index-linked HIV testing (ILHIVT), whereby children living with adults with HIV are targeted for testing, has the potential to identify high-risk, difficult to access children and adolescents, and to improve yield [9, 12, 13].

While WHO guidelines recommend offering testing to children of HIV-positive adults, countries in Eastern and Southern Africa have yet to integrate this policy into routine service delivery [9, 12, 14]. The paucity of data on effectiveness, cost and cost-effectiveness of ILHIVT may be one factor preventing its scale up. As there are no costing studies of ILHIVT within sub-Saharan Africa, the cost implications and cost-effectiveness of including this strategy within HIV service delivery programs is unknown.

The Bridging the Gap in HIV testing and care for Children in Zimbabwe (B-GAP) study assessed the effectiveness and cost of a multi-option ILHIVT strategy in both urban and rural settings in Zimbabwe [14]. This paper is the cost analysis of B-GAP estimating the cost of providing standard of care (SoC) HIV testing –voluntary, facility based HIV testing and counselling (HTC) – comparing to the incremental cost of different ILHIVT strategies.

Methods

B-GAP HIV testing intervention

In the B-GAP study, individuals with HIV enrolled in and attending care at study clinics, i.e. indexes, were offered HIV testing for any children and adolescents (aged 2–18 years) of unknown HIV status in their household by study staff. Indexes could choose one of three testing options for the child (ren)/adolescent(s): Clinic-based diagnostic testing using a rapid test; home-based rapid diagnostic testing by a healthcare provider; or home-based, caregiver-provider testing using an oral mucosal transudate (OMT) test. All participants diagnosed with HIV were linked to care at their nearest healthcare facility.

Study setting

ILHIVT was provided at 9 of the 36 primary health care facilities in Bulawayo and Mangwe district in Matebeleland South province in Zimbabwe, (6 urban, 3 rural) selected based on size and accessibility [14]. Adult HIV prevalence in both these provinces is approximately 20% [14]. The facilities do not routinely employ ILHIVT. Cost data collection took place at 2 urban facilities in Bulawayo, and 1 rural facility located in the Mangwe, sampled by convenience (Table 1).

Table 1 Characteristics of costing study facilities, as of Sept 2018
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Costing methods

We estimated the provider cost of facility level HIV testing and the provision of index-linked testing, following the Global Health Cost Consortium costing guidelines [15]. A combination of bottom-up and top-down costing was employed. First, we estimated the full cost of testing and diagnosis of children and adolescents through SoC facility testing for a 4-month time period before the B-GAP intervention (May– August 2018). We then estimated the incremental cost of ILHIVT and diagnosis of participants (September– December 2018) at the same 3 clinics, provided by the three modalities: clinic, health-care worker testing in the household, and caregiver-testing in the household. Costs estimated included personnel, consumables, overheads, building, equipment, training, start-up and transaction costs, but excluded any research related costs.

To gauge personnel time, we undertook a combination of direct observation and face-to-face interviews with clinic and B-GAP staff to quantify resources utilized to deliver all HIV testing models. We used prospective time-tracking diaries and direct observation to measure human resource time spent on different activities. Appendix 1 provides a summarized breakdown of time spent on ILHIVT activities. Prices of test kits were taken from the National Pharmaceutical Corporation of Zimbabwe (NatPharm), as specified by the centralized Matebeleland South pharmacy system. Overheads and other shared clinic costs were allocated to the testing activities based on area of the clinic utilized by each department and patient load depending on the line item.

All resources used were converted into costs using financial data collected from B-GAP project accounts, Bulawayo City Council and the district and provincial medical offices in Matebeleland South. Salaries of study staff who conducted ILHIVT, were substituted with those of facility primary care counsellors who would carry out this work in routine clinical settings. Equipment, building, training and start-up costs were annualized using expected length of life determined by WHO cost effectiveness and strategic planning prices for tradable goods, and discounted at a rate of 3% [16]. Due to the instability of the Zimbabwean currency, we estimated costs in US dollars. We converted all real-time gross settlement (RTGS) dollars, the Zimbabwean currency, into USD using the exchange rate at the time when the financial data was provided, using the Reserve Bank of Zimbabwe exchange rates [17]. All costs were converted to 2019 constant USD using the GDP deflator for the United States [18]. A detailed description of the cost data collection methods is provided in Appendix 2 and 3.

Healthcare outputs

We used clinic registers to determine the outputs of the standard facility-based HIV testing service including numbers of: tests administered; HIV positive test results; tests administered to 2–18 year olds; positive test results among 2–18 year olds. We used B-GAP study data to determine the outputs of the three ILHIVT modalities, including the number of: index cases screened; children and adolescents identified through index cases; children and adolescents tested by the three modalities; HIV-positive children and adolescents diagnosed.

Data analysis

Unit cost per SoC HIV test in clinics, and per diagnosis at each clinic were calculated by dividing the total 4 month costs of testing at each clinic by the total number of people tested, and the number identified as positive, respectively. As no additional resources were consumed at clinics to test children/adolescents we assumed the cost per test to be the same as for adults.

The incremental cost of ILHIVT was calculated by assessing the additional personnel time and resources to follow-up cases and test them. To obtain the incremental cost per test, the incremental cost was divided by the total number of children and adolescents who were tested using the respective modality. The cost per diagnosis of a positive child/adolescent was calculated as the incremental cost per test divided by the number who tested positive. The relationship between uptake and unit cost was explored by plotting the incremental ILHIVT cost per test, against uptake per modality.

Sensitivity analysis

A univariate sensitivity analysis was performed on input variables for which there was a degree of uncertainty, or that constituted a significant portion of the total costs including the exchange rate and transaction costs. The impact of the RTGS conversion rate used (1USD:4 RTGS) was assessed by varying the conversion rate to the highest (1USD:1 RTGS) and lowest (1USD: 50 RTGS) observed rates during the study period. The impact of assumptions made around resource use items such as staff salaries (±5–10%,), building (±10–20%), equipment (±10–20%) and overhead costs (±10–20%) and the frequency of the refresher training (1/year – 4/year) were also tested. In addition, HIV prevalence of clinic attendees was varied from 5 to 20%, while yield of ILHIVT was varied from 2 to 7%. Finally, transaction costs defined as management costs incurred through non-governmental organization (NGO) supervision of intervention activities (for study staff), was varied (±10–20%).

Scenario analysis

HIV self-testing is recommended by the WHO as an alternative HIV testing strategy for scale-up [19,20,21], and qualitative work conducted after the conclusion of the ILHIVT intervention indicated that lack of exposure to, and acceptability of caregiver-provided testing affected the uptake of this modality across all sites. We explored variations in the uptake of index-linked caregiver provided HIV testing to reflect potential real-world acceptability and implementation scenarios: 1.) equal uptake of all 3 modalities; 2.) a 50–50 split between facility based testing and testing performed by caregivers; 3.) 100% uptake of caregiver-provided testing at all clinics. Additionally, we compared the efficiency of home-based and caregiver-provided testing (i.e. non facility-based options) by identifying the uptake of caregiver provided tests required to match the unit cost of home-based ILHIVT performed by health care workers.

Results

Cost composition

Table 2 presents recurrent and capital costs for SoC HIV testing and the three ILHIVT modalities. The total monthly cost of providing SoC testing ranged from US$997 to US$1410. Across these facilities, personnel costs accounted for 56.9 to 70.9% of total costs; testing-specific consumables accounted for 27.9 to 35.7%; overheads from 1.2 to 9.8%, and less than 1% of total costs were attributable to capital resource items. The total incremental monthly cost of providing ILHIVT ranged from $379 to $400 in clinic; $359 to $420 for home-based testing; $255 to $288 for caregiver-provided testing. Across all three clinics and modalities; personnel costs accounted for 39.7 to 62.4% of total costs; testing-specific consumables accounted for 4.5 to 23.1%; transaction costs from 17.6 to 29.1%; capital resource items for 2.6 to 6.4%.

Table 2 Monthly cost breakdown of providing: 1.) Full SoC HTS at 2 urban and 1 rural clinic in Bulawayo and Mangwe District in Matebeleland South Province, Zimbabwe; 2.) Incremental ILHIVT according to 3 modalities – clinic, home-based and caregiver – at the same 3 clinics
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HIV testing outcomes

From May 2018 to August 2018, 2317 clinic based SoC HIV tests were administered (Table 3). The test yield (proportion of test results that were positive), was 12.9% (299/2317 total tested). Across the 3 clinics 11.5% (267/2317) of those tested were 2–18 years of age, and the yield was 3.7% (10/267).

Table 3 Unit cost of the various HIV testing modalities across all three costing study clinics, over a 4 month time-period
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The 3 clinics screened 2087 index-cases, identified 1708 eligible children and adolescents of unknown HIV status, and of those, tested 1263 (74%); 41% in clinic, 48% via home-based testing, and 10% through assisted testing. Uptake of each modality varied by clinic; home-based testing was the preferred option at urban clinics A (45.7%) and B (65.9%), while clinic testing was the preferred option at rural clinic C (56.2%). The yield of ILHIVT at Clinics A, B and C was 0.6% (3/505), 0.3% (1/290) and 1.5% (7/468) respectively. Yield by modality is as follows: 1.3% (7/523) via clinic; 0.5% (3/611) via home-based; 0.8% (1/129) via caregiver-assisted testing (Table 3).

Unit costs

The cost per child/adolescent tested through SoC ranged from US$5.90 to US$7.15. The cost per positive SoC test result ranged from US$ 35.92 to US$61.61. The costs per HIV-positive child or adolescent, 2–18 years of age identified through SoC were US$166.69, US$139.76, US$197.80 at Clinic A, B and C respectively (Table 3).

The average incremental cost per child/adolescent tested through ILHIVT at the clinic ranged from US$10.56 (urban clinic A) to US$25.47 (rural clinic C). The incremental cost per modality across all clinics ranged as follows: clinic – US$5.36 (clinic C) to US$31.08 (clinic B); home-based testing by health care worker – US$6.69 (clinic A) to US$8.65 (clinic C); caregiver-provided testing – US$17.59 (clinic A) to US$62.40 (clinic C). The cost per diagnosis of an HIV positive child/adolescent through ILHIVT ranged from US$352.59 to US$1492.02 for clinic based ILHIVT and US$817.21 to US$1545.41 via home-based testing by health care worker. Clinic C had the only positive test result from caregiver-provided testing, which cost US$998.41 (Table 3). The uptake of ILHIVT via modality and associated incremental cost per test indicates that costs are likely dependent on quantity: the fewer tests administered via modality, the higher the associated incremental unit cost per test, and vice versa (Fig. 1).

Fig. 1
figure 1

Uptake of Index-Linked HIV Testing vs associated Incremental Cost per Test, according to modality: Clinic; Caregiver; Home-Based

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Sensitivity analysis

All 4 HIV testing unit costs (SoC and ILHIVT via 3 modalities) were most sensitive to changes in the conversion rate. Figures 2a – d present the results of the sensitivity analysis performed on the remaining variables. With regards to resource use inputs, personnel salaries had the largest influence on SoC unit costs (±3–7%), followed by overheads and the addition of up to 4 refresher trainings. Changes to capital resource inputs had a negligible effect on SoC unit costs. When considering the resource use inputs for ILHIVT across all three modalities, the unit cost per test was most sensitive to changes in clinic attendee HIV prevalence (±9–13%), followed by personnel salaries for all 3 modalities .

Fig. 2
figure 2

a. Tornado plot of model parameters varied in univariate sensitivity analysis of Adolescent SoC HTS and impact on Cost per Test. b. Tornado plot of model parameters varied in univariate sensitivity analysis of Index-Linked Testing via Clinic modality and impact on Cost per Test. c. Tornado plot of model parameters varied in univariate sensitivity analysis of Index-Linked Testing via Home-Based modality and impact on Cost per Test. d. Tornado plot of model parameters varied in univariate sensitivity analysis of Index-Linked Testing via Caregiver modality and impact on Cost per Test

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The impact of changing the parameters on cost per diagnosis unit costs are presented in Supplementary Fig. 1. Cost per diagnoses were most sensitive to changes in the conversion rate. Of the resource use inputs, personnel costs had the largest influence on SoC unit costs, while changes to clinic attendee HIV prevalence as well as testing yield, had the largest influence on ILHIVT related unit costs.

Scenario analysis

The results of varying modality uptake and the subsequent impact on unit cost per test, compared to observed unit costs for the 4-month period in this study are presented in Table 4. If all 3 modalities have equal uptake, the unit cost of home-based testing increases and caregiver-provided testing becomes cheaper than clinic testing at urban clinics. If clinic and caregiver-provided testing have equal uptake, the unit cost of clinic testing decreases at both urban clinics but increases at the rural clinic, while unit costs of caregiver-provided testing at all three clinics decrease substantially. If all index-linked testing is via caregiver-provided testing, the cost per test at Clinic A, B and C respectively, are as follows: US$2.12, US$6.52, US$5.32.

Table 4 Scenario analysis of varying index-linked modality preference/uptake across all clinics: change in Unit Cost – Cost per Test
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In order for the caregiver – provided testing incremental unit cost per test to equate to that of ILHIVT via the home-based testing modality observed in the same 4-month time period, 163, 241 and 177 caregiver-provided tests would need to be administered at clinics A, B and C respectively. If all participants at clinics A and C who chose home-based testing had opted for caregiver-provided testing instead, it might have been possible to observe the lower situational caregiver – provided testing unit cost per test.

Discussion

Our findings show that 6 times more children/adolescents were tested via ILHIVT compared to SoC HIV testing over the observed period. HIV prevalence among children/adolescents accessing SoC HIV testing (4%), was much higher than children/adolescents (0.7%) tested via ILHIVT. The cost of SoC HIV testing was lower in urban than rural settings, due to a greater number of tests administered at the urban clinics (44–71% more) and larger catchment populations. The cost of ILHIVT modalities were dependent on, and varied according to uptake. Costs involved in delivering SoC HTS were primarily driven by personnel followed by consumables. Whereas personnel followed by transaction costs were the largest drivers of ILHIVT costs at both urban and rural clinics. While management costs will be an important component of ensuring quality as well as accountability in strategies such as this that rely on identifying potential cases and outreach to the community, the management of this type of service delivery may need to be streamlined in an effort to keep transaction costs low.

The cost of delivering HIV testing through standard clinic-based services in this study ranged from US$5.90 to US$7.15, and is comparable to recent STAR project estimates from Malawi, Zambia and Zimbabwe (2016 US$4.24 to US$7.65) [22], yet higher compared to the results of a systematic review evaluating the cost of HTC in South Africa (2017/2018 US$3.62) [23]. The cost per positive diagnosis through standard clinic services in this study was lower than STAR estimates (US$73.63 to US$178.92) and likely reflects the higher HIV prevalence of those accessing testing among our study population (13%), compared to the STAR project (7%) [22].

In contrast, the high cost per diagnosis associated with ILHIVT was due to a low prevalence of HIV among index-linked children. An estimated > 90% of children living with HIV are vertically infected; those who were born prior to the scale up of prevention of mother to child transmission (PMTCT) programs are now likely to be adolescents and would therefore be diagnosed only when symptomatic, resulting in worse outcomes than those diagnosed and initiated on treatment in infancy [13, 24]. SoC HIV testing is likely to diagnose children with advanced disease, whereas asymptomatic children may not be brought to the clinic. Other studies of the same age-group in Zimbabwe found higher prevalence (2.6–15%) [11, 25], and index-linked testing of sexual partners and biological children in 3 rural provinces found a 30% HIV prevalence [12]. A study in Cameroon where only 46.2% of indexes consented to have their children tested, diagnosed HIV infection in 6.8% of children tested [24], while another index-linked study in Lesotho found an HIV prevalence of 1.8% among biological children of indexes [26]. The low HIV prevalence among index cases at the B-GAP clinics is likely attributable to recent HIV testing campaigns potentially resulting in saturation of testing, including a large Population Services International testing campaign operating in the area and exclusion of children/adolescents tested > 6 months prior to B-Gap screening.

HIV case finding will become more costly as knowledge of HIV status and treatment coverage increase. Alternative community based HIV testing strategies such as home-based testing and HIV Self-Test have been evaluated using costing studies [19, 27, 28], but this is the first costing study to evaluate index-linked testing, a strategy proposed by the WHO in order to expand HTC [29]. Our results provide the first unit costs of the different ILHVIT modalities for sub-Saharan Africa but they do not provide information on the cost-effectiveness of the strategy. While a full economic evaluation is necessary to accurately estimate the cost-effectiveness of ILHIVT, Phillips et al. (2019) have shown that cost per diagnosis can be used as a proxy for cost-effectiveness of HIV testing programs, and estimated a value for the cost-effectiveness threshold (2018) US$315 per HIV diagnosis [30]. By this definition, none of the index-linked modalities in our analysis would be considered cost-effective as the lowest cost per diagnosis estimated was US$385.35. However, our sensitivity analysis illustrated that when ILHIVT yield was increased from 0.7 to 7%, (as observed in Cameroon [24]), all but two modalities (clinic testing at an urban clinic, and rural caregiver-provided testing), resulted in cost per diagnoses below that US$315 threshold. ILHIVT cost per diagnosis would be more cost-effective if targeted to a higher-prevalence population. For example, a more efficient solution for scaling up ILHIVT could be to test the entire household; costs would be shared across a greater number of tests and yield would likely increase as adults have a higher prevalence of HIV compared to children/adolescents – although measures would need to be in place to ensure services screen out those previously diagnosed and on ART [27], and those testing are effectively linked to HIV treatment or prevention. A scale-up of any version of ILHIVT – in its current format, or expanded to the entire household – to either the regional or national level, requires careful consideration of the implications of potential (dis) economies of scale as well as other cost drivers. While this study explored drivers of cost at the facility level, and expected uptake is critical to this setting, physical capacity and infrastructure investment costs necessitate scrutiny at the regional or national level [31]. Furthermore, costs involved in geographical variability with regards to transport, training, management, monitoring and evaluation, quality assurance, as well as socio-cultural variability and acceptability affecting demand, must be considered [32].

HIV self-testing has the advantages of convenience, discretion and confidentiality, compared to clinic based HTS [33, 34]. HIV self-test has shown high acceptability and uptake elsewhere which resulted in WHO guidelines recommending scale-up [19,20,21]. In this study ‘self-test’ however referred to caregiver assisted testing of a child/adolescent. Caregiver uncertainty about correctly administering the test to a child without the aid of a health care professional, as well as fear of how to counsel a child with a positive result, could be factors accounting for the low levels of uptake within this study [35]. SoC clinic based HIV testing, when supplemented with HIV self-testing, can be a cost-effective testing option in a population with a high HIV prevalence and has the capacity to extend coverage rates, and therefore diagnoses [28, 33]. In this study, because assisted-testing had very low uptake, the incremental unit costs were 3.0 times greater than the cheapest modality (home–based) in an urban setting, and 11.6 times higher than the cheapest modality (clinic) in a rural setting. This low uptake raises questions around the differences of administering a self-test to someone else, compared to self-administration. Exploration into the dynamics and differences between HIV self-test and assisted self-test are needed.

To our knowledge, this study is the first to estimate the cost of ILHIVT in any setting. A limitation is that only 3 clinics were included. Although both urban and rural clinics are represented, showing that the cost and efficiency of each modality varies according to setting, it should be noted that the urban and rural clinics were located in different districts. While Bulawayo is an entirely urban district, and Mangwe an entirely rural district, there may be unique structural and/or district level factors which also influence unit costs. Additionally, the study was conducted within an economically unstable context. Zimbabwe dollarized its economy in 2008 following hyperinflation. In 2018 it introduced its own currency (RTGS), which triggered rapid inflation. In this study all RTGS amounts were converted to USD at the prevailing rate. Costs were highly sensitive to conversion rate as a result of the rapid inflation of RTGS against the US dollar.

Conclusion

Innovative and alternative HIV testing strategies above SoC approaches are necessary in order to reach children and adolescents, given the additional barriers they face in order to get tested. The results of our study confirm that both costs and uptake of ILHIVT vary with setting. In addition, while ILHIVT allows for greater access of this difficult to reach population, compared to the standard method, uptake is a key driver of the cost per test. To ensure efficiency when scaling up ILHIVT, acceptability of testing modality needs to be considered and alternative index linked testing solutions that increase yield such as ILHIVT of the entire household, as opposed to solely targeting children/adolescents, need to be explored. Additionally, there is potential to benefit from economies of scope by integrating ILHIVT with other activities, however this would require further consideration and research.