The basic concept underlying our method.

<p>The basic concept underlying our method.</p

Cost effectiveness analyses.

<p>Footnotes:</p><p>All costs are in US$.</p>a<p>TDF dominant over ZDV because of lower costs and higher QALYs.</p

Summary of key variables and main influences in model.

<p>Effects of vaccine are illustrated in grey.</p

Characteristics of the population up to and at baseline (year 2025).^*

<p>*all values relate to 2025 unless stated.</p><p>Characteristics of the population up to and at baseline (year 2025).^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107214#nt101" target="_blank">*</a>}</p

This plots hypothetical pathways of resistance emergence against zidovudine (1A) or tenofovir (1B & 1C) used in this simulation.

<p>The transition probabilities given next to arrows are per 3 months spent on a failing treatment with an (unmeasured) HIV RNA >500 copies/mL. Due to scarcity of resistance data of failing tenofovir regimens from developing settings two separate pathways were tested in the simulation. The base scenario (1B) was derived from a limited set of sequences from tenofovir failures and does not include the multidrug resistance pattern Q151M. The pessimistic scenario (1C) is based on estimations from sequences obtained after virological failure with stavudine and allows for extensive multidrug (i.e. Q151M) resistance emergence. Also note that the multidrug resistance patterns in the zidovudine pathway were not observed in the data (enframed by dashed lines), but were assumed to occur at low frequency. Abbreviations: ZDV, Zidovudine; TDF, tenofovir; S, susceptible; I, intermediate resistant; R, fully resistant.</p

Uncertainty bounds of incremental cost effectiveness (ICER) estimates, % of ICER estimates suggesting dominance of the tenofovir (TDF) treatment strategy and % of ICER estimates below the WHO threshold for high cost-effectiveness.

<p>Results were obtained by repeatedly drawing one simulation with TDF as the initial strategy and one simulation with zidovudine (ZDV) in the initial treatment. From this pair of simulations the incremental cost effectiveness ratio was calculated. Dominance was defined by lower costs and higher quality adjusted life year estimates for a specific treatment. By repeating this process 1000 times we obtained an estimate for how frequently the TDF strategy was dominant. Analogous calculations were performed to check how often the ICER estimates were below the WHO threshold for high cost effectiveness (annual per capita gross domestic product of US$ 2154). Uncertainty bounds reflect ranges that include 95% of all ICER estimates.</p><p>Abbreviations: ICER, incremental cost effectiveness ratio; TDF, tenofovir; WHO, World Health Organization.</p

Selected model input parameters.

<p>Selected model input parameters.</p

Multivariable uncertainty analysis based on 500 runs.

<p>Variation in effect of vaccine on HIV incidence under parameter variation, sampling from distributions of parameter values given in Supplementary Methods and Results in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107214#pone.0107214.s001" target="_blank">File S1</a>.</p><p>Multivariable uncertainty analysis based on 500 runs.</p

Shows different outcomes of first-line therapy by type of initial combination antiretroviral therapy (either including zidovudine [ZDV] or tenofovir [TDF]).

<p>For individuals starting with TDF, resistance emergence was modelled by two different scenarios (also see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042834#pone-0042834-g001" target="_blank">Figures 1B and 1C</a>): a base scenario (red symbols) and a pessimistic scenario (blue symbols). Abbreviations: cART, combination antiretroviral therapy; WHO, World Health Organization.</p

Predicted outcomes 2025–2060 of eight vaccine introduction scenarios in 2025.

<p>(i) prevention efficacy 0.0, viral load efficacy 0.0 log₁₀, (ii) prevention efficacy 30%, viral load efficacy 0.0 log₁₀, (iii) prevention efficacy 50%, viral load efficacy 0.0 log₁₀, (iv) prevention efficacy 90%, viral load efficacy 0.0 log₁₀, (v) prevention efficacy 0.0, viral load efficacy 1.0 log₁₀, (vi) prevention efficacy 0.0, viral load efficacy 2.0 log₁₀, (vii) prevention efficacy 50%, viral load efficacy 1.0 log₁₀, (viii) prevention efficacy 90%, viral load efficacy 2.0 log₁₀. All in the context of vaccination at 15, with a rate of vaccination per 3 months of 0.3 amongst those age 15–17 (and a 5 year catch-up program amongst adults age 18–30 covering 50% of the population of that age), with a maximum coverage (in 15–17 year olds) of 70%, and with regular boosters every 5 years (the assumed duration of vaccine effect) with 80% of people being adherent to these boosts.</p