6
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Projected effectiveness and added value of HIV vaccination campaigns in South Africa: A modeling study

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Promising multi-dose HIV vaccine regimens are being tested in trials in South Africa. We estimated the potential epidemiological and economic impact of HIV vaccine campaigns compared to continuous vaccination, assuming that vaccine efficacy is transient and dependent on immune response. We used a dynamic economic mathematical model of HIV transmission calibrated to 2012 epidemiological data to simulate vaccination with anticipated antiretroviral treatment scale-up in South Africa. We estimate that biennial vaccination with a 70% efficacious vaccine reaching 20% of the sexually active population could prevent 480,000–650,000 HIV infections (13.8–15.3% of all infections) over 10 years. Assuming a launch price of $15 per dose, vaccination was found to be cost-effective, with an incremental cost-effectiveness ratio of $13,746 per quality-adjusted life-year as compared to no vaccination. Increasing vaccination coverage to 50% will prevent more infections but is less likely to achieve cost-effectiveness. Campaign vaccination is consistently more effective and costs less than continuous vaccination across scenarios. Results suggest that a partially effective HIV vaccine will have substantial impact on the HIV epidemic in South Africa and offer good value if priced less than $105 for a five-dose series. Vaccination campaigns every two years may offer greater value for money than continuous vaccination reaching the same coverage level.

          Related collections

          Most cited references33

          • Record: found
          • Abstract: found
          • Article: not found

          Increased HIV-1 vaccine efficacy against viruses with genetic signatures in Env-V2

          Summary The RV144 trial demonstrated 31% vaccine efficacy (VE) at preventing HIV-1 infection 1 . Antibodies against the HIV-1 envelope variable loops 1 and 2 (V1/V2) domain correlated inversely with infection risk 2 . We hypothesized that vaccine-induced immune responses against V1/V2 would selectively impact, or sieve, HIV-1 breakthrough viruses. 936 HIV-1 genome sequences from 44 vaccine and 66 placebo recipients were examined. We show that vaccine-induced immune responses were associated with two signatures in V1/V2 at amino-acid positions 169 and 181. VE against viruses matching the vaccine at position 169 was 48% (CI: 18 to 66%; p=0.0036), whereas VE against viruses mismatching the vaccine at position 181 was 78% (CI: 35% to 93%; p=0.0028). Residue 169 is in a cationic glycosylated region recognized by broadly neutralizing and RV144-derived antibodies. The predicted distance between the two signatures sites (21±7 Å), and their match/mismatch dichotomy, suggest that multiple factors may be involved in the protection observed in RV144. Genetic signatures of RV144 vaccination in V2 complement the finding of an association between high V1/V2 binding antibodies and reduced risk of HIV-1 acquisition and provide evidence that vaccine-induced V2 responses plausibly played a role in the partial protection conferred by the RV144 regimen.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Immune correlates of vaccine protection against HIV-1 acquisition

            The partial efficacy reported in the RV144 HIV vaccine trial in 2009 has driven the HIV vaccine field to define correlates of risk associated with HIV-1 acquisition and connect these functionally to preventing HIV infection. Immunological correlates, mainly including CD4(+) T cell responses to the HIV envelope and Fc-mediated antibody effector function, have been connected to reduced acquisition. These immunological correlates place immunological and genetic pressure on the virus. Indeed, antibodies directed at conserved regions of the V1V2 loop and antibodies that mediate antibody-dependent cellular cytotoxicity to HIV envelope in the absence of inhibiting serum immunoglobulin A antibodies correlated with decreased HIV risk. More recently, researchers have expanded their search with nonhuman primate studies using vaccine regimens that differ from that used in RV144; these studies indicate that non-neutralizing antibodies are associated with protection from experimental lentivirus challenge as well. These immunological correlates have provided the basis for the design of a next generation of vaccine regimens to improve upon the qualitative and quantitative degree of magnitude of these immune responses on HIV acquisition.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical models

              New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per μL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral therapy accordingly. We aimed to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy and expanded treatment coverage. We used several independent mathematical models in four settings-South Africa (generalised epidemic, moderate antiretroviral therapy coverage), Zambia (generalised epidemic, high antiretroviral therapy coverage), India (concentrated epidemic, moderate antiretroviral therapy coverage), and Vietnam (concentrated epidemic, low antiretroviral therapy coverage)-to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy under scenarios of existing and expanded treatment coverage, with results projected over 20 years. Analyses assessed the extension of eligibility to include individuals with CD4 counts of 500 cells per μL or less, or all HIV-positive adults, compared with the previous (2010) recommendation of initiation with CD4 counts of 350 cells per μL or less. We assessed costs from a health-system perspective, and calculated the incremental cost (in US$) per disability-adjusted life-year (DALY) averted to compare competing strategies. Strategies were regarded very cost effective if the cost per DALY averted was less than the country's 2012 per-head gross domestic product (GDP; South Africa: $8040; Zambia: $1425; India: $1489; Vietnam: $1407) and cost effective if the cost per DALY averted was less than three times the per-head GDP. In South Africa, the cost per DALY averted of extending eligibility for antiretroviral therapy to adult patients with CD4 counts of 500 cells per μL or less ranged from $237 to $1691 per DALY averted compared with 2010 guidelines. In Zambia, expansion of eligibility to adults with a CD4 count threshold of 500 cells per μL ranged from improving health outcomes while reducing costs (ie, dominating the previous guidelines) to $749 per DALY averted. In both countries results were similar for expansion of eligibility to all HIV-positive adults, and when substantially expanded treatment coverage was assumed. Expansion of treatment coverage in the general population was also cost effective. In India, the cost for extending eligibility to all HIV-positive adults ranged from $131 to $241 per DALY averted, and in Vietnam extending eligibility to patients with CD4 counts of 500 cells per μL or less cost $290 per DALY averted. In concentrated epidemics, expanded access for key populations was also cost effective. Our estimates suggest that earlier eligibility for antiretroviral therapy is very cost effective in low-income and middle-income settings, although these estimates should be revisited when more data become available. Scaling up antiretroviral therapy through earlier eligibility and expanded coverage should be considered alongside other high-priority health interventions competing for health budgets. Bill & Melinda Gates Foundation, WHO. Copyright © 2014 Eaton et al. Open Access article distributed under the terms of CC BY-NC-ND. Published by .. All rights reserved.
                Bookmark

                Author and article information

                Contributors
                ddimitro@fredhutch.org
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                17 April 2018
                17 April 2018
                2018
                : 8
                : 6066
                Affiliations
                [1 ]ISNI 0000 0001 2173 6322, GRID grid.411418.9, CHU Sainte-Justine Research Centre, ; Montreal, Canada
                [2 ]ISNI 0000 0001 2292 3357, GRID grid.14848.31, School of Public Health, , University of Montreal, ; Montreal, Canada
                [3 ]ISNI 0000000122986657, GRID grid.34477.33, The Comparative Health Outcomes, Policy, and Economics (CHOICE) Institute, , School of Pharmacy, University of Washington, ; Seattle, WA USA
                [4 ]ISNI 0000 0001 2180 1622, GRID grid.270240.3, Vaccine and Infectious Disease Division, , Fred Hutchinson Cancer Research Center, ; Seattle, USA
                [5 ]ISNI 0000000122986657, GRID grid.34477.33, Department of Applied Mathematics, , University of Washington, ; Seattle, Washington USA
                Article
                24268
                10.1038/s41598-018-24268-4
                5904131
                29666455
                710ff110-7159-40fa-9ec4-1c3bdcf98fb7
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 4 October 2017
                : 26 March 2018
                Categories
                Article
                Custom metadata
                © The Author(s) 2018

                Uncategorized
                Uncategorized

                Comments

                Comment on this article