Top

International Journal of Public Health

Published in:

Open Access 01-07-2019 | Vaccination | Original article

The future of a partially effective HIV vaccine: assessing limitations at the population level

Authors: Christian Selinger, Dobromir T. Dimitrov, Philip A. Welkhoff, Anna Bershteyn

Published in: International Journal of Public Health | Issue 6/2019

Abstract

Objectives

Mathematical models have unanimously predicted that a first-generation HIV vaccine would be useful and cost-effective to roll out, but that its overall impact would be insufficient to reverse the epidemic. Here, we explore what factors contribute most to limiting the impact of such a vaccine.

Methods

Ranging from a theoretical ideal to a more realistic regimen, mirroring the one used in the currently ongoing trial in South Africa (HVTN 702), we model a nested hierarchy of vaccine attributes such as speed of scale-up, efficacy, durability, and return rates for booster doses.

Results

The predominant reasons leading to a substantial loss of vaccine impact on the HIV epidemic are the time required to scale up mass vaccination, limited durability, and waning of efficacy.

Conclusions

A first-generation partially effective vaccine would primarily serve as an intermediate milestone, furnishing correlates of immunity and platforms that could serve to accelerate future development of a highly effective, durable, and scalable next-generation vaccine capable of reversing the HIV epidemic.

Available only for authorised users

Adamson B, Dimitrov D, Devine B, Barnabas R (2017) The potential cost-effectiveness of HIV vaccines: a systematic review. Pharmacoecon Open 1(1):1–12. https://doi.org/10.1007/s41669-016-0009-9 CrossRefPubMedPubMedCentral

Andersson KM, Stover J (2011) The potential impact of a moderately effective HIV vaccine with rapidly waning protection in South Africa and Thailand. Vaccine 29(36):6092–9. https://doi.org/10.1016/j.vaccine.2011.06.060 CrossRefPubMed

Attia S, Egger M, Müller M, Zwahlen M, Low N (2009) Sexual transmission of HIV according to viral load and antiretroviral therapy: systematic review and meta-analysis. AIDS 23(11):1397–404. https://doi.org/10.1097/QAD.0b013e32832b7dca CrossRefPubMed

Beauclair R, Hens N, Delva W (2018) The role of age-mixing patterns in HIV transmission dynamics: novel hypotheses from a field study in Cape Town, South Africa. Epidemics 25:61–71. https://doi.org/10.1016/j.epidem.2018.05.006 CrossRefPubMed

Bershteyn A, Klein DJ, Wenger E, Eckhoff PA (2012) Description of the EMOD-HIV Model v0.7. ArXiv e-prints 1206.3720

Bershteyn A, Klein DJ, Eckhoff PA (2013) Age-dependent partnering and the HIV transmission chain: a microsimulation analysis. J R Soc Interface 10(88):20130613. https://doi.org/10.1098/rsif.2013.0613 CrossRefPubMedPubMedCentral

Bershteyn A, Mutai KK, Akullian AN, Klein DJ, Jewell BL, Mwalili SM (2018) The influence of mobility among high-risk populations on HIV transmission in Western Kenya. Infect Dis Model 3:97–106. https://doi.org/10.1016/j.idm.2018.04.001 CrossRefPubMedPubMedCentral

CDC (2016) Vaccination coverage among adults in the United States, National Health Interview Survey. https://www.cdc.gov/vaccines/imz-managers/coverage/adultvaxview/pubs-resources/NHIS-2016.html

Celum CL, Delany-Moretlwe S, McConnell M, van Rooyen H, Bekker LG, Kurth A, Bukusi E, Desmond C, Morton J, Baeten JM (2015) Rethinking HIV prevention to prepare for oral PrEP implementation for young African women. J Int AIDS Soc 18(4 Suppl 3):20227PubMedPubMedCentral

ClinicalTrails (2017) Pivotal phase 2b/3 ALVAC/bivalent gp120/MF59 HIV vaccine prevention safety and efficacy study in South Africa. https://clinicaltrials.gov/ct2/show/NCT02968849. Accessed 2017-03-31

Coffee M, Lurie MN, Garnett GP (2007) Modelling the impact of migration on the HIV epidemic in South Africa. AIDS 21(3):343–350. https://doi.org/10.1097/qad.0b013e328011dac9 CrossRefPubMed

Connolly C, Simbayi LC, Shanmugam R, Nqeketo A (2008) Male circumcision and its relationship to HIV infection in South Africa: results of a national survey in 2002. S Afr Med J 98(10):789–94PubMed

de Montigny S, Adamson BJS, Mâsse BR, Garrison LP, Kublin JG, Gilbert PB, Dimitrov DT (2018) Projected effectiveness and added value of HIV vaccination campaigns in South Africa: a modeling study. Sci Rep 8(1):6066. https://doi.org/10.1038/s41598-018-24268-4 CrossRefPubMedPubMedCentral

de Oliveira T, Kharsany ABM, Gräf T, Cawood C, Khanyile D, Grobler A, Puren A, Madurai S, Baxter C, Karim QA, Karim SSA (2017) Transmission networks and risk of HIV infection in KwaZulu-Natal, South Africa: a community-wide phylogenetic study. Lancet HIV 4(1):e41–e50. https://doi.org/10.1016/S2352-3018(16)30186-2 CrossRefPubMed

Delany-Moretlwe S, Kelley KF, James S, Scorgie F, Subedar H, Dlamini NR, Pillay Y, Naidoo N, Chikandiwa A, Rees H (2018) Human papillomavirus vaccine introduction in South Africa: implementation lessons from an evaluation of the national school-based vaccination campaign. Glob Health Sci Pract 6(3):425–438. https://doi.org/10.9745/ghsp-d-18-00090 CrossRefPubMedPubMedCentral

Dobra A, Bärnighausen T, Vandormael A, Tanser F (2017) Space-time migration patterns and risk of HIV acquisition in rural South Africa. AIDS 31(1):137–145. https://doi.org/10.1097/qad.0000000000001292 CrossRefPubMed

Donnell D, Baeten JM, Kiarie J, Thomas KK, Stevens W, Cohen CR, McIntyre J, Lingappa JR, Celum C (2010) Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis. Lancet 375(9731):2092–8. https://doi.org/10.1016/S0140-6736(10)60705-2 CrossRefPubMedPubMedCentral

Eaton LA, Kalichman S (2007) Risk compensation in HIV prevention: implications for vaccines, microbicides, and other biomedical HIV prevention technologies. Curr HIV/AIDS Rep 4(4):165–172CrossRefPubMedPubMedCentral

Eaton JW, Menzies NA, Stover J, Cambiano V, Chindelevitch L, Cori A, Hontelez JAC, Humair S, Kerr CC, Klein DJ, Mishra S, Mitchell KM, Nichols BE, Vickerman P, Bakker R, Brnighausen T, Bershteyn A, Bloom DE, Boily MC, Chang ST, Cohen T, Dodd PJ, Fraser C, Gopalappa C, Lundgren J, Martin NK, Mikkelsen E, Mountain E, Pham QD, Pickles M, Phillips A, Platt L, Pretorius C, Prudden HJ, Salomon JA, van de Vijver DAMC, de Vlas SJ, Wagner BG, White RG, Wilson DP, Zhang L, Blandford J, Meyer-Rath G, Remme M, Revill P, Sangrujee N, Terris-Prestholt F, Doherty M, Shaffer N, Easterbrook PJ, Hirnschall G, Hallett TB (2013) Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical models. Lancet Glob Health 2(1):23–34. https://doi.org/10.1016/S2214-109X(13)70172-4 CrossRefPubMedPubMedCentral

Eaton JW, Bacar N, Bershteyn A, Cambiano V, Cori A, Dorrington RE, Fraser C, Gopalappa C, Hontelez JAC, Johnson LF, Klein DJ, Phillips AN, Pretorius C, Stover J, Rehle TM, Hallett TB (2015) Assessment of epidemic projections using recent HIV survey data in South Africa: a validation analysis of ten mathematical models of HIV epidemiology in the antiretroviral therapy era. Lancet Glob Health 3(10):e598–608. https://doi.org/10.1016/S2214-109X(15)00080-7 CrossRefPubMed

Garnett GP, Hallett TB, Takaruza A, Hargreaves J, Rhead R, Warren M, Nyamukapa C, Gregson S (2016) Providing a conceptual framework for HIV prevention cascades and assessing feasibility of empirical measurement with data from east Zimbabwe: a case study. Lancet HIV 3(7):e297–306. https://doi.org/10.1016/S2352-3018(16)30039-X CrossRefPubMedPubMedCentral

Hankins CA, Glasser JW, Chen RT (2011) Modeling the impact of RV144-like vaccines on HIV transmission. Vaccine 29(36):6069–71. https://doi.org/10.1016/j.vaccine.2011.07.001 CrossRefPubMedPubMedCentral

Harling G, Tanser F, Mutevedzi T, Bärnighausen T (2015) Assessing the validity of respondents’ reports of their partners’ ages in a rural South African population-based cohort. BMJ Open 5(3):e005638. https://doi.org/10.1136/bmjopen-2014-005638 CrossRefPubMedPubMedCentral

Harmon TM, Fisher KA, McGlynn MG, Stover J, Warren MJ, Teng Y, Nveke A (2016) Exploring the potential health impact and cost-effectiveness of AIDS vaccine within a comprehensive HIV/AIDS response in low- and middle-income countries. PLoS ONE 11(1):e0146387. https://doi.org/10.1371/journal.pone.0146387 CrossRefPubMedPubMedCentral

Hontelez JAC, Nagelkerke N, Bärnighausen T, Bakker R, Tanser F, Newell ML, Lurie MN, Baltussen R, de Vlas SJ (2011) The potential impact of RV144-like vaccines in rural South Africa: a study using the STDSIM microsimulation model. Vaccine 29(36):6100–6. https://doi.org/10.1016/j.vaccine.2011.06.059 CrossRefPubMedPubMedCentral

Johnson LF, Dorrington RE, Moolla H (2017a) HIV epidemic drivers in South Africa: a model-based evaluation of factors accounting for inter-provincial differences in HIV prevalence and incidence trends. S Afr J HIV Med. https://doi.org/10.4102/sajhivmed.v18i1.695 CrossRef

Johnson LF, Dorrington RE, Moolla H (2017b) Progress towards the 2020 targets for HIV diagnosis and antiretroviral treatment in South Africa. S Afr J HIV Med. https://doi.org/10.4102/sajhivmed.v18i1.694 CrossRef

Keeling MJ, Shattock A (2012) Optimal but unequitable prophylactic distribution of vaccine. Epidemics 4(2):78–85. https://doi.org/10.1016/j.epidem.2012.03.001 CrossRefPubMedPubMedCentral

Klein DJ (2012) Relationship formation and flow control algorithms for generating age-structured networks in HIV modeling. In: 2012 IEEE 51st IEEE conference on decision and control (CDC). IEEE. https://doi.org/10.1109/cdc.2012.6426573

Klein DJ, Bershteyn A, Eckhoff PA (2014) Dropout and re-enrollment: implications for epidemiological projections of treatment programs. AIDS 28(Suppl 1):S47–S59. https://doi.org/10.1097/QAD.0000000000000081 CrossRefPubMed

MacPhail CL, Sayles JN, Cunningham W, Newman PA (2012) Perceptions of sexual risk compensation following posttrial HIV vaccine uptake among young South Africans. Qual Health Res 22(5):668–678. https://doi.org/10.1177/1049732311431944 CrossRefPubMedPubMedCentral

Marconi VC, Grandits G, Okulicz JF, Wortmann G, Ganesan A, Crum-Cianflone N, Polis M, Landrum M, Dolan MJ, Ahuja SK, Agan B, Kulkarni H (2011) Cumulative viral load and virologic decay patterns after antiretroviral therapy in HIV-infected subjects influence CD4 recovery and AIDS. PLoS ONE 6(5):e17956. https://doi.org/10.1371/journal.pone.0017956 CrossRefPubMedPubMedCentral

Medlock J, Pandey A, Parpia AS, Tang A, Skrip LA, Galvani AP (2017) Effectiveness of UNAIDS targets and HIV vaccination across 127 countries. Proc Natl Acad Sci USA 114(15):4017–4022. https://doi.org/10.1073/pnas.1620788114 CrossRefPubMed

Moodley N, Gray G, Bertram M (2016a) Projected economic evaluation of the national implementation of a hypothetical HIV vaccination program among adolescents in South Africa, 2012. BMC Public Health 16:330. https://doi.org/10.1186/s12889-016-2959-3 CrossRefPubMedPubMedCentral

Moodley N, Gray G, Bertram M (2016b) The case for adolescent HIV vaccination in South Africa: a cost-effectiveness analysis. Medicine 95(4):e2528. https://doi.org/10.1097/MD.0000000000002528 CrossRefPubMedPubMedCentral

Mugglin C, Wandeler G, Estill J, Egger M, Bender N, Davies MA, Keiser O (2013) Retention in care of HIV-infected children from HIV test to start of antiretroviral therapy: systematic review. PLoS ONE 8(2):e56446. https://doi.org/10.1371/journal.pone.0056446 CrossRefPubMedPubMedCentral

Ott MQ, Bärnighausen T, Tanser F, Lurie MN, Newell ML (2011) Age-gaps in sexual partnerships: seeing beyond ’sugar daddies’. AIDS 25(6):861–3. https://doi.org/10.1097/QAD.0b013e32834344c9 CrossRefPubMedPubMedCentral

Pettifor A, Bekker LG, Hosek S, DiClemente R, Rosenberg M, Bull SS, Allison S, Delany-Moretlwe S, Kapogiannis BG, Cowan F (2013) Preventing HIV among young people: research priorities for the future. J Acquir Immune Defic Syndr 63(2 Suppl):S155–S160. https://doi.org/10.1097/QAI.0b013e31829871fb CrossRefPubMedPubMedCentral

Phillips AN, Cambiano V, Nakagawa F, Ford D, Lundgren JD, Roset-Bahmanyar E, Roman F, Effelterre TV (2014) Potential future impact of a partially effective HIV vaccine in a southern African setting. PLoS ONE 9(9):e107214. https://doi.org/10.1371/journal.pone.0107214 CrossRefPubMedPubMedCentral

Rehle T, Shisana O, Pillay V, Zuma K, Puren A, Parker W (2007) National HIV incidence measures-new insights into the South African epidemic. S Afr Med J 97(3):194–9PubMed

Robb ML, Rerks-Ngarm S, Nitayaphan S, Pitisuttithum P, Kaewkungwal J, Kunasol P, Khamboonruang C, Thongcharoen P, Morgan P, Benenson M, Paris RM, Chiu J, Adams E, Francis D, Gurunathan S, Tartaglia J, Gilbert P, Stablein D, Michael NL, Kim JH (2012) Risk behaviour and time as covariates for efficacy of the HIV vaccine regimen ALVAC-HIV (vCP1521) and AIDSVAX B/E: a post-hoc analysis of the Thai phase 3 efficacy trial RV 144. Lancet Infect Dis 12(7):531–7. https://doi.org/10.1016/S1473-3099(12)70088-9 CrossRefPubMedPubMedCentral

Rubincam C, Newman PA, Atujuna M, Bekker LG (2018) ‘Why would you promote something that is less percent safer than a condom?’ Perspectives on partially effective HIV prevention technologies among key populations in South Africa. SAHARA J J Soc Asp HIV/AIDS 15(1):179–186. https://doi.org/10.1080/17290376.2018.1536561 CrossRef

Russell ND, Marovich MA (2016) Pox-protein public private partnership program and upcoming HIV vaccine efficacy trials. Curr Opin HIV AIDS 11(6):614–619. https://doi.org/10.1097/COH.0000000000000322 CrossRefPubMed

Sayles JN, Macphail CL, Newman PA, Cunningham WE (2009) Future HIV vaccine acceptability among young adults in South Africa. Health Educ Behav 37(2):193–210. https://doi.org/10.1177/1090198109335654 CrossRefPubMedPubMedCentral

Selinger C, Bershteyn A, Dimitrov D, Hallett TB, Bekker LG, Rees H, Gray G (2017) Population-level impact and cost-effectiveness of an HIV vaccine in South Africa. In: CROI2017, Seattle, WA. http://www.croiconference.org/sessions/population-level-impact-and-cost-effectiveness-hiv-vaccine-south-africa. Accessed 1 Apr 2019

Selinger C, Bershteyn A, Dimitrov DT, Adamson BJ, Revill P, Hallett TB, Phillips A, Bekker LG, Rees H, Gray G (2019) Targeting and vaccine durability are key for population-level impact and cost-effectiveness of a pox-protein HIV vaccine regimen in South Africa. Vaccine 37(16):2258–2267. https://doi.org/10.1016/j.vaccine.2019.02.073 CrossRefPubMed

Shisana O, Simbayi L (2002) Nelson Mandela/HSRC study of HIV/AIDS: South African national HIV prevalence, behavioural risks and mass media: household survey 2002. HSRC Press, Cape Down

Shisana O, Rehle T, Simbayi L, Zuma K, Jooste S, Pillay-Van Wyk V, Mbelle N, Van Zyl J, Parker W, Zungu N, Pezi S, Implementation Team SABSSMIII (2010) South African national HIV prevalence, incidence, behaviour and communication survey 2008: a turning tide among teenagers?. HSRC Press, Cape Town

Shisana O, Rehle T, Simbayi LC, Zuma K, Jooste S, Zungu N, Labadarios D, Onoya D, Wabiri N (2014) South African national HIV prevalence, incidence and behaviour survey 2012. HSRC Press, Cape Town. http://www.hsrc.ac.za/uploads/pageContent/4565/SABSSM IV LEO final.pdf. Accessed 1 Apr 2019

Smith JA, Anderson SJ, Harris KL, McGillen JB, Lee E, Garnett GP, Hallett TB (2016) Maximising HIV prevention by balancing the opportunities of today with the promises of tomorrow: a modelling study. Lancet HIV 3(7):e289–96. https://doi.org/10.1016/S2352-3018(16)30036-4 CrossRefPubMedPubMedCentral

South African National AIDS Council (2016) South African HIV and TB investment case. http://sanac.org.za/wp-content/uploads/2016/03/1603-Investment-Case-Report-LowRes-18-Mar.pdf. Accessed 2017-05-10

Statistics South Africa (2014) Mortality and causes of death in South Africa, 2012: findings from death notification. Statistics South Africa, Pretoria

Unaids (2016) Global AIDS update 2016. http://www.unaids.org/sites/default/files/media_asset/global-AIDS-update-2016_en.pdf. Accessed 2017-05-09

Unaids (2018) Global AIDS update 2018. http://www.unaids.org/sites/default/files/media_asset/unaids-data-2018_en.pdf. Accessed 2018-12-12

UnitedNations (2016) World population prospects. Population Division, United Nations. http://esa.un.org/unpd/wpp/DVD/. Accessed 1 Apr 2019

Voeten HACM, Vissers DCJ, Gregson S, Zaba B, White RG, de Vlas SJ, Habbema JDF (2009) Strong association between in-migration and HIV prevalence in Urban Sub-Saharan Africa. Sex Transm Dis. https://doi.org/10.1097/olq.0b013e3181c3f2d0 CrossRef

Title: The future of a partially effective HIV vaccine: assessing limitations at the population level
Authors: Christian Selinger
Dobromir T. Dimitrov
Philip A. Welkhoff
Anna Bershteyn
Publication date: 01-07-2019
Publisher: Springer International Publishing
Keywords: Vaccination
Human Immunodeficiency Virus
Published in: International Journal of Public Health / Issue 6/2019
Print ISSN: 1661-8556
Electronic ISSN: 1661-8564
DOI: https://doi.org/10.1007/s00038-019-01234-z

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

The future of a partially effective HIV vaccine: assessing limitations at the population level

Abstract

Objectives

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Objectives

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 6/2019

Direct healthcare costs of spinal disorders in Brazil

Urban–rural differentials in age-related biological risk among middle-aged and older Chinese

Association between human papillomavirus and chlamydia trachomatis infection risk in women: a systematic review and meta-analysis

Clusters of risk behaviors for noncommunicable diseases in the Brazilian adult population

Status of birth and pregnancy outcome capture in Health Demographic Surveillance Sites in 13 countries

Correction to: Attendance to cervical cancer screening among Roma and non-Roma women living in North-Western region of Romania