Addressing Pediatric HIV Pretreatment Drug Resistance and Virologic Failure in Sub-Saharan Africa: A Cost-Effectiveness Analysis of Diagnostic-Based Strategies in Children ≥3 Years Old
Abstract
:1. Introduction
2. Materials and Methods
2.1. Overview
2.2. HIV Model
2.3. ART Regimen Assumptions
2.4. Health and Economic Outcomes
2.5. Sensitivity Analyses
2.6. Scenario Analyses
3. Results
3.1. Health Outcomes
3.2. Costs
3.3. Cost-Effectiveness
3.4. Sensitivity Analyses
3.5. Scenario Analyses
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Boerma, R.S.; Sigaloff, K.C.; Akanmu, A.S.; Inzaule, S.; Boele van Hensbroek, M.; Rinke de Wit, T.F.; Calis, J.C. Alarming increase in pretreatment HIV drug resistance in children living in sub-Saharan Africa: A systematic review and meta-analysis. J. Antimicrob. Chemother. 2017, 72, 365–371. [Google Scholar] [CrossRef] [Green Version]
- Kityo, C.; Boerma, R.S.; Sigaloff, K.C.E.; Kaudha, E.; Calis, J.C.J.; Musiime, V.; Balinda, S.; Nakanjako, R.; Boender, T.S.; Mugyenyi, P.N.; et al. Pretreatment HIV drug resistance results in virological failure and accumulation of additional resistance mutations in Ugandan children. J. Antimicrob. Chemother. 2017, 72, 2587–2595. [Google Scholar] [CrossRef] [Green Version]
- WHO. Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection: Recommendations for a Public Health Approach; World Health Organization: Geneva, Switezerland, 2013. [Google Scholar]
- Violari, A.; Lindsey, J.C.; Hughes, M.D.; Mujuru, H.A.; Barlow-Mosha, L.; Kamthunzi, P.; Chi, B.H.; Cotton, M.F.; Moultrie, H.; Khadse, S.; et al. Nevirapine versus ritonavir-boosted lopinavir for HIV-infected children. N. Engl. J. Med. 2012, 366, 2380–2389. [Google Scholar] [CrossRef] [PubMed]
- Palumbo, P.; Lindsey, J.C.; Hughes, M.D.; Cotton, M.F.; Bobat, R.; Meyers, T.; Bwakura-Dangarembizi, M.; Chi, B.H.; Musoke, P.; Kamthunzi, P.; et al. Antiretroviral treatment for children with peripartum nevirapine exposure. N. Engl. J. Med. 2010, 363, 1510–1520. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kanthula, R.; Rossouw, T.M.; Feucht, U.D.; van Dyk, G.; Beck, I.A.; Silverman, R.; Olson, S.; Salyer, C.; Cassol, S.; Frenkel, L.M. Persistence of HIV drug resistance among South African children given nevirapine to prevent mother-to-child-transmission. AIDS 2017, 31, 1143–1148. [Google Scholar] [CrossRef] [PubMed]
- Jain, V.; Sucupira, M.C.; Bacchetti, P.; Hartogensis, W.; Diaz, R.S.; Kallas, E.G.; Janini, L.M.; Liegler, T.; Pilcher, C.D.; Grant, R.M.; et al. Differential persistence of transmitted HIV-1 drug resistance mutation classes. J. Infect. Dis. 2011, 203, 1174–1181. [Google Scholar] [CrossRef] [Green Version]
- Carlucci, J.G.; Liu, Y.; Friedman, H.; Pelayo, B.E.; Robelin, K.; Sheldon, E.K.; Clouse, K.; Vermund, S.H. Attrition of HIV-exposed infants from early infant diagnosis services in low- and middle-income countries: A systematic review and meta-analysis. J. Int. Aids Soc. 2018, 21, e25209. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- UNAIDS. Global HIV & AIDS Statistics—2020 Fact Sheet. Available online: https://www.unaids.org/en/resources/fact-sheet (accessed on 15 December 2020).
- Adedimeji, A.; Edmonds, A.; Hoover, D.; Shi, Q.; Sinayobye, J.D.; Nduwimana, M.; Lelo, P.; Nash, D.; Anastos, K.; Yotebieng, M. Characteristics of HIV-Infected Children at Enrollment into Care and at Antiretroviral Therapy Initiation in Central Africa. PLoS ONE 2017, 12, e0169871. [Google Scholar] [CrossRef] [Green Version]
- Davies, M.A.; Phiri, S.; Wood, R.; Wellington, M.; Cox, V.; Bolton-Moore, C.; Timmerman, V.; Moultrie, H.; Ndirangu, J.; Rabie, H.; et al. Temporal trends in the characteristics of children at antiretroviral therapy initiation in southern Africa: The IeDEA-SA Collaboration. PLoS ONE 2013, 8, e81037. [Google Scholar] [CrossRef] [Green Version]
- Fatti, G.; Bock, P.; Eley, B.; Mothibi, E.; Grimwood, A. Temporal trends in baseline characteristics and treatment outcomes of children starting antiretroviral treatment: An analysis in four provinces in South Africa, 2004-2009. J. Acquir. Immune Defic. Syndr. 2011, 58, e60–e67. [Google Scholar] [CrossRef] [Green Version]
- Sutcliffe, C.G.; Bolton-Moore, C.; van Dijk, J.H.; Cotham, M.; Tambatamba, B.; Moss, W.J. Secular trends in pediatric antiretroviral treatment programs in rural and urban Zambia: A retrospective cohort study. BMC Pediatr. 2010, 10, 54. [Google Scholar] [CrossRef] [Green Version]
- WHO. Update of Recommendations on First- and Second-Line Antiretroviral Regimens; World Health Organization: Geneva, Switzerland, 2019. [Google Scholar]
- Bollen, P.D.J.; Moore, C.L.; Mujuru, H.A.; Makumbi, S.; Kekitiinwa, A.R.; Kaudha, E.; Parker, A.; Musoro, G.; Nanduudu, A.; Lugemwa, A.; et al. Simplified dolutegravir dosing for children with HIV weighing 20 kg or more: Pharmacokinetic and safety substudies of the multicentre, randomised ODYSSEY trial. Lancet HIV 2020, 7, e533–e544. [Google Scholar] [CrossRef]
- Jesson, J.; Desmonde, S.; Yiannoutsos, C.T.; Patten, G.; Malateste, K.; Duda, S.N.; Kumarasamy, N.; Yotebieng, M.; Davies, M.A.; Musick, B.; et al. Weight-for-age distributions among children with HIV on antiretroviral therapy in the International epidemiology Databases to Evaluate AIDS (IeDEA) multiregional consortium. BMC Res. Notes 2020, 13, 249. [Google Scholar] [CrossRef]
- WHO. Considerations for Introducing New Antiretroviral Drug Formulations for Children: Policy Brief; World Health Organization: Geneva, Switzerland, 2020. [Google Scholar]
- The Lancet HIV. End resistance to dolutegravir roll-out. Lancet HIV 2020, 7, e593. [CrossRef]
- Inzaule, S.C.; Ondoa, P.; Peter, T.; Mugyenyi, P.N.; Stevens, W.S.; de Wit, T.F.R.; Hamers, R.L. Affordable HIV drug-resistance testing for monitoring of antiretroviral therapy in sub-Saharan Africa. Lancet Infect. Dis. 2016, 16, e267–e275. [Google Scholar] [CrossRef]
- Phillips, A.N.; Cambiano, V.; Nakagawa, F.; Revill, P.; Jordan, M.R.; Hallett, T.B.; Doherty, M.; De Luca, A.; Lundgren, J.D.; Mhangara, M.; et al. Cost-effectiveness of public-health policy options in the presence of pretreatment NNRTI drug resistance in sub-Saharan Africa: A modelling study. Lancet HIV 2018, 5, e146–e154. [Google Scholar] [CrossRef] [Green Version]
- Phillips, A.N.; Cambiano, V.; Miners, A.; Revill, P.; Pillay, D.; Lundgren, J.D.; Bennett, D.; Raizes, E.; Nakagawa, F.; De Luca, A.; et al. Effectiveness and cost-effectiveness of potential responses to future high levels of transmitted HIV drug resistance in antiretroviral drug-naive populations beginning treatment: Modelling study and economic analysis. Lancet HIV 2014, 1, e85–e93. [Google Scholar] [CrossRef] [Green Version]
- Nichols, B.E.; Sigaloff, K.C.; Kityo, C.; Hamers, R.L.; Baltussen, R.; Bertagnolio, S.; Jordan, M.R.; Hallett, T.B.; Boucher, C.A.; de Wit, T.F.; et al. Increasing the use of second-line therapy is a cost-effective approach to prevent the spread of drug-resistant HIV: A mathematical modelling study. J. Int. Aids Soc. 2014, 17, 19164. [Google Scholar] [CrossRef]
- Duarte, H.A.; Babigumira, J.B.; Enns, E.A.; Stauffer, D.C.; Shafer, R.W.; Beck, I.A.; Garrison, L.P., Jr.; Chung, M.H.; Frenkel, L.M.; Bendavid, E. Cost-effectiveness analysis of pre-ART HIV drug resistance testing in Kenyan women. EClinicalMedicine 2020, 22, 100355. [Google Scholar] [CrossRef]
- WHO. HIV Drug Resistance Report 2019; World Health Organization: Geneva, Switzerland, 2019. [Google Scholar]
- Hamers, R.L.; Schuurman, R.; Sigaloff, K.C.; Wallis, C.L.; Kityo, C.; Siwale, M.; Mandaliya, K.; Ive, P.; Botes, M.E.; Wellington, M.; et al. Effect of pretreatment HIV-1 drug resistance on immunological, virological, and drug-resistance outcomes of first-line antiretroviral treatment in sub-Saharan Africa: A multicentre cohort study. Lancet Infect. Dis. 2012, 12, 307–317. [Google Scholar] [CrossRef]
- Ehrenkranz, P.D.; Baptiste, S.L.; Bygrave, H.; Ellman, T.; Doi, N.; Grimsrud, A.; Jahn, A.; Kalua, T.; Nyirenda, R.K.; Odo, M.O.; et al. The missed potential of CD4 and viral load testing to improve clinical outcomes for people living with HIV in lower-resource settings. PLoS Med. 2019, 16, e1002820. [Google Scholar] [CrossRef] [Green Version]
- The Collaborative Initiative for Paediatric HIV Education; Research (CIPHER) Global Cohort Collaboration. Incidence of switching to second-line antiretroviral therapy and associated factors in children with HIV: An international cohort collaboration. Lancet HIV 2019, 6, e105–e115. [Google Scholar] [CrossRef]
- Boerma, R.S.; Boender, T.S.; Bussink, A.P.; Calis, J.C.; Bertagnolio, S.; Rinke de Wit, T.F.; Boele van Hensbroek, M.; Sigaloff, K.C. Suboptimal Viral Suppression Rates Among HIV-Infected Children in Low- and Middle-Income Countries: A Meta-analysis. Clin. Infect. Dis. 2016, 63, 1645–1654. [Google Scholar] [CrossRef] [Green Version]
- Wools-Kaloustian, K.; Marete, I.; Ayaya, S.; Sohn, A.H.; Van Nguyen, L.; Li, S.; Leroy, V.; Musick, B.S.; Newman, J.E.; Edmonds, A.; et al. Time to First-Line ART Failure and Time to Second-Line ART Switch in the IeDEA Pediatric Cohort. J. Acquir. Immune Defic. Syndr. 2018, 78, 221–230. [Google Scholar] [CrossRef]
- Davies, M.A.; Moultrie, H.; Eley, B.; Rabie, H.; Van Cutsem, G.; Giddy, J.; Wood, R.; Technau, K.; Keiser, O.; Egger, M.; et al. Virologic failure and second-line antiretroviral therapy in children in South Africa--the IeDEA Southern Africa collaboration. J. Acquir. Immune Defic. Syndr. 2011, 56, 270–278. [Google Scholar] [CrossRef] [PubMed]
- Murphy, R.A.; Court, R.; Maartens, G.; Sunpath, H. Second-Line Antiretroviral Therapy in Sub-Saharan Africa: It Is Time to Mind the Gaps. Aids Res. Hum. Retrovir. 2017, 33, 1181–1184. [Google Scholar] [CrossRef] [PubMed]
- Lecher, S.; Ellenberger, D.; Kim, A.A.; Fonjungo, P.N.; Agolory, S.; Borget, M.Y.; Broyles, L.; Carmona, S.; Chipungu, G.; De Cock, K.M.; et al. Scale-up of HIV Viral Load Monitoring—Seven Sub-Saharan African Countries. Morb. Mortal. Wkly. Rep. 2015, 64, 1287–1290. [Google Scholar] [CrossRef] [Green Version]
- Marston, M.; Becquet, R.; Zaba, B.; Moulton, L.H.; Gray, G.; Coovadia, H.; Essex, M.; Ekouevi, D.K.; Jackson, D.; Coutsoudis, A.; et al. Net survival of perinatally and postnatally HIV-infected children: A pooled analysis of individual data from sub-Saharan Africa. Int. J. Epidemiol. 2011, 40, 385–396. [Google Scholar] [CrossRef]
- Ciaranello, A.L.; Morris, B.L.; Walensky, R.P.; Weinstein, M.C.; Ayaya, S.; Doherty, K.; Leroy, V.; Hou, T.; Desmonde, S.; Lu, Z.; et al. Validation and calibration of a computer simulation model of pediatric HIV infection. PLoS ONE 2013, 8, e83389. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ciaranello, A.L.; Doherty, K.; Penazzato, M.; Lindsey, J.C.; Harrison, L.; Kelly, K.; Walensky, R.P.; Essajee, S.; Losina, E.; Muhe, L.; et al. Cost-effectiveness of first-line antiretroviral therapy for HIV-infected African children less than 3 years of age. AIDS 2015, 29, 1247–1259. [Google Scholar] [CrossRef] [Green Version]
- Department of Health and Human Services. Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Exposed and HIV-Infected Children. Panel on Opportunistic Infections in HIV-Exposed and HIV-Infected Children. J. Pediatric Infect. Dis. Soc. 2013, 2, 293–308. [Google Scholar]
- Ciaranello, A.; Lu, Z.; Ayaya, S.; Losina, E.; Musick, B.; Vreeman, R.; Freedberg, K.A.; Abrams, E.J.; Dillabaugh, L.; Doherty, K.; et al. Incidence of World Health Organization stage 3 and 4 events, tuberculosis and mortality in untreated, HIV-infected children enrolling in care before 1 year of age: An IeDEA (International Epidemiologic Databases To Evaluate AIDS) East Africa regional analysis. Pediatric Infect. Dis. J. 2014, 33, 623–629. [Google Scholar] [CrossRef] [Green Version]
- Desmonde, S.; Neilan, A.M.; Musick, B.; Patten, G.; Chokephaibulkit, K.; Edmonds, A.; Duda, S.N.; Malateste, K.; Wools-Kaloustian, K.; Ciaranello, A.L.; et al. Time-varying age- and CD4-stratified rates of mortality and WHO stage 3 and stage 4 events in children, adolescents and youth 0 to 24 years living with perinatally acquired HIV, before and after antiretroviral therapy initiation in the paediatric IeDEA Global Cohort Consortium. J. Int. Aids Soc. 2020, 23, e25617. [Google Scholar] [CrossRef] [PubMed]
- United Nations, Department of Economic and Social Affairs Population Dynamics. Population Division (2019). World Population Prospects 2019, Online Edition. Available online: https://population.un.org/wpp/Download/Standard/Population/ (accessed on 15 November 2020).
- Dugdale, C.M.; Ciaranello, A.L.; Bekker, L.G.; Stern, M.E.; Myer, L.; Wood, R.; Sax, P.E.; Abrams, E.J.; Freedberg, K.A.; Walensky, R.P. Risks and Benefits of Dolutegravir- and Efavirenz-Based Strategies for South African Women With HIV of Child-Bearing Potential: A Modeling Study. Ann. Intern. Med. 2019. [Google Scholar] [CrossRef] [PubMed]
- Boerma, R.S.; Bunupuradah, T.; Dow, D.; Fokam, J.; Kariminia, A.; Lehman, D.; Kityo, C.; Musiime, V.; Palumbo, P.; Schoffelen, A.; et al. Multicentre analysis of second-line antiretroviral treatment in HIV-infected children: Adolescents at high risk of failure. J. Int. Aids Soc. 2017, 20, 21930. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Carlucci, J.G.; Liu, Y.; Clouse, K.; Vermund, S.H. Attrition of HIV-positive children from HIV services in low and middle-income countries. AIDS 2019, 33, 2375–2386. [Google Scholar] [CrossRef] [PubMed]
- Global Fund. Global Fund Pooled Procurement Price List July 2020. Available online: https://www.theglobalfund.org/media/5813/ppm_arvreferencepricing_table_en.pdf (accessed on 1 August 2020).
- Institute for Health Metrics and Evaluation (IHME). Health Service Provision in Kenya: Assessing Facility Capacity, Costs of Care, and Patient Perspectives; IHME: Seattle, WA, USA, 2014. [Google Scholar]
- Institute for Health Metrics and Evaluation (IHME). Health Service Provision in Ghana: Assessing Facility Capacity, Costs of Care, and Patient Perspectives; IHME: Seattle, WA, USA, 2015. [Google Scholar]
- Institute for Health Metrics and Evaluation (IHME). Health Service Provision in Uganda: Assessing Facility Capacity, Costs of Care, and Patient Perspectives; IHME: Seattle, WA, USA, 2014. [Google Scholar]
- Institute for Health Metrics and Evaluation (IHME). Health Service Provision in Zambia: Assessing Facility Capacity, Costs of Care, and Patient Perspectives; IHME: Seattle, WA, USA, 2014. [Google Scholar]
- WHO-CHOICE. Estimates of Unit Costs for Patient Services for South Africa. Available online: https://www.who.int/choice/country/zaf/cost/en/ (accessed on 23 November 2019).
- Sanders, G.D.; Neumann, P.J.; Basu, A.; Brock, D.W.; Feeny, D.; Krahn, M.; Kuntz, K.M.; Meltzer, D.O.; Owens, D.K.; Prosser, L.A.; et al. Recommendations for Conduct, Methodological Practices, and Reporting of Cost-effectiveness Analyses: Second Panel on Cost-Effectiveness in Health and Medicine. JAMA 2016, 316, 1093–1103. [Google Scholar] [CrossRef]
- Drain, P.K.; Dorward, J.; Violette, L.R.; Quame-Amaglo, J.; Thomas, K.K.; Samsunder, N.; Ngobese, H.; Mlisana, K.; Moodley, P.; Donnell, D.; et al. Point-of-care HIV viral load testing combined with task shifting to improve treatment outcomes (STREAM): Findings from an open-label, non-inferiority, randomised controlled trial. Lancet HIV 2020, 7, e229–e237. [Google Scholar] [CrossRef]
- WHO Commission on Macroeconomics and Health & World Health Organization. Macroeconomics and Health: Investing in Health for Economic Development—Executive Summary; World Health Organization: Geneva, Switzerland, 2001. [Google Scholar]
- World Bank. World Bank Open Data. Available online: https://data.worldbank.org/ (accessed on 25 December 2020).
- Zheng, A.; Kumarasamy, N.; Huang, M.; Paltiel, A.D.; Mayer, K.H.; Rewari, B.B.; Walensky, R.P.; Freedberg, K.A. The cost-effectiveness and budgetary impact of a dolutegravir-based regimen as first-line treatment of HIV infection in India. J. Int. Aids Soc. 2018, 21, e25085. [Google Scholar] [CrossRef] [PubMed]
- Vitoria, M.; Hill, A.; Ford, N.; Doherty, M.; Clayden, P.; Venter, F.; Ripin, D.; Flexner, C.; Domanico, P.L. The transition to dolutegravir and other new antiretrovirals in low-income and middle-income countries: What are the issues? AIDS 2018, 32, 1551–1561. [Google Scholar] [CrossRef]
Parameter | Base-Case Estimate | Range for Sensitivity Analyses | Source |
---|---|---|---|
Probability of virologic failure a | |||
Initial ART (over 12 months) | |||
No PDR on NNRTI-based ART | 19.2% | 16.8–24.6% | Boerma et al. [28], Kityo et al. [2] |
PDR on PI-based ART | 19.2% | ||
PDR on NNRTI-based ART | 64.1% | 39.5–75.2% | |
Dolutegravir-based ART | 9.1% | Boerma et al. [28], Dugdale et al. [40] | |
Second-line ART (over 24 months) | |||
PI-based ART after NNRTI-based first-line ART | 16.4% | 13.9–19.4% | Boerma et al. [41] |
PI-based ART after DTG-based first-line ART | 16.4% | 13.9–40.0% | Assumption |
Cascade of care | |||
Status quo probability of switching to second-line ART when virologic failure is diagnosed b | 40% | Assumption | |
Probability of switching to second-line ART when virologic failure is diagnosed with improved regimen switching practices | 80% | 60.0–90.0% | |
Probability of lost to follow-up (over 5 years) c | 15% | Carlucci et al. [42] | |
Unit Costs (USD) d | |||
ART annual cost | |||
NNRTI-based ART | $123 | Global Fund [43] | |
Dolutegravir-based ART | $123 | Assumption | |
PI-based ART | $290 | $123–$400 | Global Fund [43] |
Inpatient day | $96 | $15–$400 e | IHME [44,45,46,47], WHO-CHOICE [48] |
Outpatient visit | $32 | $10–$80 | IHME [44,45,46,47], WHO-CHOICE [48] |
CD4 testing | $12 | $6–$24 | Duarte et al. [23] |
Viral load testing | $54 | $10–$80 | Duarte et al. [23] |
Resistance testing | $125 | $30–$250 | Duarte et al. [23] |
Status Quo | Improved Switching | PDR Testing | DTG | DTG Improved Switching | |
---|---|---|---|---|---|
Health outcomes | |||||
Proportion of children with suppressed viral load at 5 years after ART initiation a | 63.7% | 66.2% | 65.0% | 67.4% | 68.3% |
Proportion of children alive at 5 years after ART initiation b | 69.3% | 71.2% | 71.0% | 71.4% | 72.1% |
ART outcomes | |||||
Proportion of children on PI-based ART c | 17% | 21% | 26% | 5% | 7% |
Person-months of ART use (per person) d | 82.3 | 84.1 | 83.5 | 84.4 | 85.0 |
Person-months of PI-based ART use (per person) d | 13.7 | 17.4 | 22.5 | 4.5 | 5.7 |
Undiscounted Cost (USD) | Undiscounted LYs | ||
Status quo | 1,938,996 | 7203 | |
Improved switching | 2,025,987 | 7358 | |
PDR testing | 2,203,694 | 7318 | |
DTG | 1,838,619 | 7378 | |
DTG + improved switching | 1,868,298 | 7430 | |
Discounted Cost (USD) | Discounted LYs | ICER (USD/LY gained) | |
Status quo | 1,697,253 | 6301 | N/A |
Improved switching | 1,772,844 | 6432 | 579 a |
PDR testing | 1,944,011 | 6399 | N/A |
DTG | 1,610,327 | 6448 | N/A |
DTG + improved switching | 1,636,073 | 6491 | 591 b |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Siriruchatanon, M.; Liu, S.; Carlucci, J.G.; Enns, E.A.; Duarte, H.A. Addressing Pediatric HIV Pretreatment Drug Resistance and Virologic Failure in Sub-Saharan Africa: A Cost-Effectiveness Analysis of Diagnostic-Based Strategies in Children ≥3 Years Old. Diagnostics 2021, 11, 567. https://doi.org/10.3390/diagnostics11030567
Siriruchatanon M, Liu S, Carlucci JG, Enns EA, Duarte HA. Addressing Pediatric HIV Pretreatment Drug Resistance and Virologic Failure in Sub-Saharan Africa: A Cost-Effectiveness Analysis of Diagnostic-Based Strategies in Children ≥3 Years Old. Diagnostics. 2021; 11(3):567. https://doi.org/10.3390/diagnostics11030567
Chicago/Turabian StyleSiriruchatanon, Mutita, Shan Liu, James G. Carlucci, Eva A. Enns, and Horacio A. Duarte. 2021. "Addressing Pediatric HIV Pretreatment Drug Resistance and Virologic Failure in Sub-Saharan Africa: A Cost-Effectiveness Analysis of Diagnostic-Based Strategies in Children ≥3 Years Old" Diagnostics 11, no. 3: 567. https://doi.org/10.3390/diagnostics11030567