12 research outputs found
Is a HIV vaccine a viable option and at what price? An economic evaluation of adding HIV vaccination into existing prevention programs in Thailand
<p>Abstract</p> <p>Background</p> <p>This study aims to determine the maximum price at which HIV vaccination is cost-effective in the Thai healthcare setting. It also aims to identify the relative importance of vaccine characteristics and risk behavior changes among vaccine recipients to determine how they affect this cost-effectiveness.</p> <p>Methods</p> <p>A semi-Markov model was developed to estimate the costs and health outcomes of HIV prevention programs combined with HIV vaccination in comparison to the existing HIV prevention programs without vaccination. The estimation was based on a lifetime horizon period (99 years) and used the government perspective. The analysis focused on both the general population and specific high-risk population groups. The maximum price of cost-effective vaccination was defined by using threshold analysis; one-way and probabilistic sensitivity analyses were performed. The study employed an expected value of perfect information (EVPI) analysis to determine the relative importance of parameters and to prioritize future studies.</p> <p>Results</p> <p>The most expensive HIV vaccination which is cost-effective when given to the general population was 12,000 Thai baht (US$1 = 34 Thai baht in 2009). This vaccination came with 70% vaccine efficacy and lifetime protection as long as risk behavior was unchanged post-vaccination. The vaccine would be considered cost-ineffective at any price if it demonstrated low efficacy (30%) and if post-vaccination risk behavior increased by 10% or more, especially among the high-risk population groups. The incremental cost-effectiveness ratios were the most sensitive to change in post-vaccination risk behavior, followed by vaccine efficacy and duration of protection. The EVPI indicated the need to quantify vaccine efficacy, changed post-vaccination risk behavior, and the costs of vaccination programs.</p> <p>Conclusions</p> <p>The approach used in this study differentiated it from other economic evaluations and can be applied for the economic evaluation of other health interventions not available in healthcare systems. This study is important not only for researchers conducting future HIV vaccine research but also for policy decision makers who, in the future, will consider vaccine adoption.</p
Systematic comparison of HIV-1 Envelope-specific IgG responses induced by different vaccination regimens: Can we steer IgG recognition towards regions of viral vulnerability?
Immunogens and vaccination regimens can influence patterns of immune-epitope recognition, steering them towards or away from epitopes of potential viral vulnerability. HIV-1 envelope (Env)-specific antibodies targeting variable region 2 (V2) or 3 (V3) correlated with protection during the RV144 trial, however, it was suggested that the immunodominant V3 region might divert antibody responses away from other relevant sites. We mapped IgG responses against linear Env epitopes in five clinical HIV vaccine trials, revealing a specific pattern of Env targeting for each regimen. Notable V2 responses were only induced in trials administering CRF01_AE based immunogens, but targeting of V3 was seen in all trials, with the soluble, trimeric CN54gp140 protein eliciting robust V3 recognition. Strong V3 targeting was linked to greater overall response, increased number of total recognised antigenic regions, and where present, stronger V2 recognition. Hence, strong induction of V3-specific antibodies did not negatively impact the targeting of other linear epitopes in this study, suggesting that the induction of antibodies against V3 and other regions of potential viral vulnerability need not be necessarily mutually exclusive
Molecular Evolution of the HIV-1 Thai Epidemic between the Time of RV144 Immunogen Selection to the Execution of the Vaccine Efficacy Trial
The RV144 HIV-1 vaccine trial (Thailand, 2003 to 2009), using immunogens genetically matched to the regional epidemic, demonstrated the first evidence of efficacy for an HIV-1 vaccine. Here we studied the molecular evolution of the HIV-1 epidemic from the time of immunogen selection to the execution of the efficacy trial. We studied HIV-1 genetic diversity among 390 volunteers who were deferred from enrollment in RV144 due to preexisting HIV-1 infection using a multiregion hybridization assay, full-genome sequencing, and phylogenetic analyses. The subtype distribution was 91.7% CRF01_AE, 3.5% subtype B, 4.3% B/CRF01_AE recombinants, and 0.5% dual infections. CRF01_AE strains were 31% more diverse than the ones from the 1990s Thai epidemic. Sixty-nine percent of subtype B strains clustered with the cosmopolitan Western B strains. Ninety-three percent of B/CRF01_AE recombinants were unique; recombination breakpoint analysis showed that these strains were highly embedded within the larger network that integrates recombinants from East/Southeast Asia. Compared to Thai sequences from the early 1990s, the distance to the RV144 immunogens increased 52% to 68% for CRF01_AE Env immunogens and 12% to 29% for subtype B immunogens. Forty-three percent to 48% of CRF01_AE sequences differed from the sequence of the vaccine insert in Env variable region 2 positions 169 and 181, which were implicated in vaccine sieve effects in RV144. In conclusion, compared to the molecular picture at the early stages of vaccine development, our results show an overall increase in the genetic complexity of viruses in the Thai epidemic and in the distance to vaccine immunogens, which should be considered at the time of the analysis of the trial results
Antibody to HSV gD peptide induced by vaccination does not protect against HSV-2 infection in HSV-2 seronegative women
<div><p>Background</p><p>In the HIV-1 vaccine trial RV144, ALVAC-HIV prime with an AIDSVAX<sup>Ā®</sup> B/E boost reduced HIV-1 acquisition by 31% at 42 months post first vaccination. The bivalent AIDSVAX<sup>Ā®</sup> B/E vaccine contains two gp120 envelope glycoproteins, one from the subtype B HIV-1 MN isolate and one from the subtype CRF01_AE A244 isolate. Each envelope glycoprotein harbors a highly conserved 27-amino acid HSV-1 glycoprotein D (gD) tag sequence that shares 93% sequence identity with the HSV-2 gD sequence. We assessed whether vaccine-induced anti-gD antibodies protected females against HSV-2 acquisition in RV144.</p><p>Methods</p><p>Of the women enrolled in RV144, 777 vaccine and 807 placebo recipients were eligible and randomly selected according to their pre-vaccination HSV-1 and HSV-2 serostatus for analysis. Immunoglobulin G (IgG) and IgA responses to gD were determined by a binding antibody multiplex assay and HSV-2 serostatus was determined by Western blot analysis.</p><p>Ninety-three percent and 75% of the vaccine recipients had anti-gD IgG and IgA responses two weeks post last vaccination, respectively. There was no evidence of reduction in HSV-2 infection by vaccination compared to placebo recipients over 78 weeks of follow-up. The annual incidence of HSV-2 infection in individuals who were HSV-2 negative at baseline or HSV-1 positive and HSV-2 indeterminate at baseline were 4.38/100 person-years (py) and 3.28/100 py in the vaccine and placebo groups, respectively. Baseline HSV-1 status did not affect subsequent HSV-2 acquisition. Specifically, the estimated odds ratio of HSV-2 infection by Week 78 for female placebo recipients who were baseline HSV-1 positive (n = 422) vs. negative (n = 1120) was 1.14 [95% confidence interval 0.66 to 1.94, p = 0.64)]. No evidence of reduction in the incidence of HSV-2 infection by vaccination was detected.</p><p>Conclusions</p><p>AIDSVAX<sup>Ā®</sup> B/E containing gD did not confer protection from HSV-2 acquisition in HSV-2 seronegative women, despite eliciting anti-gD serum antibodies.</p></div
IgG and IgA responses and percentage of responders to the gD protein measured at week 26 by binding antibody multiplex array for the n = 85 HIV-1-uninfected female participants in the RV144 case-control study [26] (75 vaccine and 10 placebo recipients).
<p>IgG and IgA responses and percentage of responders to the gD protein measured at week 26 by binding antibody multiplex array for the n = 85 HIV-1-uninfected female participants in the RV144 case-control study [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0176428#pone.0176428.ref026" target="_blank">26</a>] (75 vaccine and 10 placebo recipients).</p
Comparison of HSV-2 infection rates by week 78 (Vaccine vs. Placebo Female Recipients) (HSV-2 Infection = Positive or Indeterminate at Week 78).
<p>Comparison of HSV-2 infection rates by week 78 (Vaccine vs. Placebo Female Recipients) (HSV-2 Infection = Positive or Indeterminate at Week 78).</p
Comparison of the sequence of the gD tag expressed on the AIDSVAX<sup>Ā®</sup> B/E gp120 envelope glycoprotein antigens (Global Solutions for Infectious Diseases) with the corresponding published HSV-1 and HSV-2 sequences (retrieved from GenBank on 06/24/15).
<p>The amino acid sequences are shown in weblogos, depicting the different variants at each position as stacked symbols, with the height of each symbol indicating its relative frequency. Asterisks highlight the main differences between HSV-1 and HSV-2. Weblogos were constructed using [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0176428#pone.0176428.ref040" target="_blank">40</a>].</p
HSV-2 infection rates by baseline behavioral HIV-1 risk score (Primary Cohort).
<p>HSV-2 infection rates by baseline behavioral HIV-1 risk score (Primary Cohort).</p
Distribution of age (ā¤20, 21ā25, ā„26)<sup>*</sup> and baseline self-reported behavioral risk score (Percent Low, Medium, High)<sup>**</sup> for female RV144 participants with HSV measurements included in the study.
<p>Distribution of age (ā¤20, 21ā25, ā„26)<sup><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0176428#t001fn001" target="_blank">*</a></sup> and baseline self-reported behavioral risk score (Percent Low, Medium, High)<sup><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0176428#t001fn002" target="_blank">**</a></sup> for female RV144 participants with HSV measurements included in the study.</p