The COMBREX Project: Design, Methodology, and Initial Results

© 2013 Brian P. et al.Prior to the “genomic era,” when the acquisition of DNA sequence involved significant labor and expense, the sequencing of genes was strongly linked to the experimental characterization of their products. Sequencing at that time directly resulted from the need to understand an experimentally determined phenotype or biochemical activity. Now that DNA sequencing has become orders of magnitude faster and less expensive, focus has shifted to sequencing entire genomes. Since biochemistry and genetics have not, by and large, enjoyed the same improvement of scale, public sequence repositories now predominantly contain putative protein sequences for which there is no direct experimental evidence of function. Computational approaches attempt to leverage evidence associated with the ever-smaller fraction of experimentally analyzed proteins to predict function for these putative proteins. Maximizing our understanding of function over the universe of proteins in toto requires not only robust computational methods of inference but also a judicious allocation of experimental resources, focusing on proteins whose experimental characterization will maximize the number and accuracy of follow-on predictions.COMBREX is funded by a GO grant from the National Institute of General Medical Sciences (NIGMS) (1RC2GM092602-01).Peer Reviewe

Impact and Cost of the HIV/AIDS National Strategic Plan for Mozambique, 2015-2019--Projections with the Spectrum/Goals Model.

IntroductionMozambique continues to face a severe HIV epidemic and high cost for its control, largely born by international donors. We assessed feasible targets, likely impact and costs for the 2015-2019 national strategic HIV/AIDS plan (NSP).MethodsThe HIV epidemic and response was modelled in the Spectrum/Goals/Resource Needs dynamical simulation model, separately for North/Center/South regions, fitted to antenatal clinic surveillance data, household and key risk group surveys, program statistics, and financial records. Intervention targets were defined in collaboration with the National AIDS Council, Ministry of Health, technical partners and implementing NGOs, considering existing commitments.ResultsImplementing the NSP to meet existing coverage targets would reduce annual new infections among all ages from 105,000 in 2014 to 78,000 in 2019, and reduce annual HIV/AIDS-related deaths from 80,000 to 56,000. Additional scale-up of prevention interventions targeting high-risk groups, with improved patient retention on ART, could further reduce burden to 65,000 new infections and 51,000 HIV-related deaths in 2019. Program cost would increase from US$273 million in 2014, to US$ 433 million in 2019 for 'Current targets', or US$ 495 million in 2019 for 'Accelerated scale-up'. The 'Accelerated scale-up' would lower cost per infection averted, due to an enhanced focus on behavioural prevention for high-risk groups. Cost and mortality impact are driven by ART, which accounts for 53% of resource needs in 2019. Infections averted are driven by scale-up of interventions targeting sex work (North, rising epidemic) and voluntary male circumcision (Center & South, generalized epidemics).ConclusionThe NSP could aim to reduce annual new HIV infections and deaths by 2019 by 30% and 40%, respectively, from 2014 levels. Achieving incidence and mortality reductions corresponding to UNAIDS' 'Fast track' targets will require increased ART coverage and additional behavioural prevention targeting key risk groups

Infections averted (among all ages) from coverage scale-up over 2015–2019, relative to resource needs over 2015–2019, by intervention, in the ‘Accelerated scale-up’ scenario.

<p>Both costs and infections averted are discounted, at 3% per year. Abbreviations in Fig 5: ART = Antiretroviral therapy; Sex work = behavioural prevention for Female Sex Workers and their clients; HTC = HIV Testing and Counselling; MSM = Men having sex with men; IDU = Intravenous drug users; PMTCT = Prevention of Mother-to-Child Transmission; VMMC = voluntary medical male circumcision; Youth = behavioural prevention for youth in and out of schools.</p

<i>Goals</i> model fit to historical HIV prevalence trends, 3 regions of Mozambique.

<p>Surveillance/AIM represents the statistical estimates of epidemic trends as of 2014 using the Spectrum/AIM version 5.1, beta 34.</p

Service delivery unit costs (in US$).

<p>Legend to Table 2: All values in stated in $US, using a MZN conversion factor of 32 over 2014–2019. Unless indicated, unit costs are assumed to be the same across the 3 regions; changes from 2014 to 2019 in unit costs are linear, unless indicated. For costs estimated from PEPFAR expenditures, unit costs excluded USG program management and overheads. Abbreviations: ART = Antiretroviral therapy; ARV = antiretroviral; AZT = azithromycin; FSW = Female Sex Workers; IBBS = Integrated Bio-Behavioural Survey; IEC = Information, Education and Communication; MSM = Men having sex with men; NASA = National AIDS Spending Assessment; IDU = Intravenous drug users; NASA = National AIDS Spending Assessment; PMTCT = Prevention of Mother-to-Child Transmission; NVP = nevirapine; TDF = tenofovir; 3TC = lamivudine; EFV = efavirenz.</p><p>Service delivery unit costs (in US$).</p

Costs and cost drivers of the Mozambique NSP 2015–2019: a) Resource needs, by scenario and intervention; b) PLWH on first-line and second-line ART, ‘Accelerated scale-up’ scenario; c) ART cost break-down, ‘Accelerated scale-up’ scenario.

<p>In (a), the dashed line represents resources available and committed from within the national government, other Mozambican implementers, the Global Fund, PEPFAR and other donors–as of January 2015.</p

Intervention coverage, and corresponding condom usage and partner numbers, in 2019, by NSP scenario and region of Mozambique.

<p>Legend to Table 1: Scenarios: A = constant coverage at 2014 levels; B = current targets; C = Accelerated scale-up (see: Methods).</p><p>Interventions kept constant at 2014 proportional coverage across all 3 scenarios are: Peer education in the workplace (3%); cotrimoxazole prophylaxis for HIV-infected children (73%), Transfusion blood units effectively screened for HIV (95%; no health impact modelled); and STI treatment (70%; no health impact modelled).</p><p>*Condom usage and numbers of partners are calculated as a function of levels of those behaviours at the 2014 baseline, and the targeted coverage and assumed effectiveness of community mobilization, mass media, HIV testing and counselling, condom promotion, and outreach/behavioural prevention for youth, sex workers, MSM and IDU, according to the Goals impact matrix [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142908#pone.0142908.ref013" target="_blank">13</a>].</p><p>Abbreviations: ART = Antiretroviral therapy; FSW = Female Sex Workers; IBBS = Integrated Bio-Behavioural Survey; IEC = Information, Education and Communication; MSM = Men having sex with men; IDU = Intravenous drug users; PMTCT = Prevention of Mother-to-Child Transmission.</p><p>Intervention coverage, and corresponding condom usage and partner numbers, in 2019, by NSP scenario and region of Mozambique.</p