TECHNICAL UPDATE
HIV DRUG RESISTANCE
HIV DRUG RESISTANCE SURVEILLANCE GUIDANCE: 2015 UPDATE DECEMBER 2015
TECHNICAL UPDATE
HIV DRUG RESISTANCE SURVEILLANCE GUIDANCE: 2015 UPDATE DECEMBER 2015
WHO Library Cataloguing-in-Publication Data HIV drug resistance surveillance guidance – 2015 update. 1.Anti-HIV Agents – therapeutic use. 2.Drug Resistance, Viral. 3.HIV Infections – epidemiology. 4.HIV Infections – drug therapy. 5.Population Surveillance. I.World Health Organization. ISBN 978 92 4 151009 7 (NLM classification: WC 503.2)
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TABLE OF CONTENTS Acronyms and abbreviations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Introduction .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Main components. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 1. EWI of HIVDR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4 5 5 6 7 7
2. Surveillance of HIVDR: high-priority activities.
2.1 Surveillance of PDR in populations initiating ART .. 2.2 Surveillance of ADR in populations receiving ART.
3. Surveillance of HIVDR: activities for specific circumstances.
3.1 Surveillance of HIVDR among treatment-naive infant less than 18 months old. .
Use of data for ART programme optimization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 EWI of HIVDR. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8 8 8 8
Surveillance of PDR in populations initiating ART. Surveillance of ADR in populations receiving ART.
Surveillance of HIVDR among infants less than 18 months old ..
Annex: Generic budgets. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Table A1. Estimated budget for PDR surveillance among ART initiators. Table A2. Generic budget for ADR surveillance (12-month time point). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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10 11 12 13 14
Table A3. Generic budget for ADR surveillance (48+ month time point).
Table A4. Generic budget for ADR surveillance (combined 12 month and 48+ month time point). Table A5. Generic budget for combined PDR and ADR surveillance. .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Table A6. Generic budget for surveillance of HIVDR among treatment-naive infant less than 18 months old.
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ACRONYMS AND ABBREVIATIONS ADR ART DBS EID EWI Acquired HIV drug resistance Antiretroviral therapy Dried blood spot Early infant diagnosis Early warning indicators HIV drug resistance Pre-treatment HIV drug resistance World Health Organization
HIVDR PDR
WHO
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INTRODUCTION Unprecedented scale-up of antiretroviral therapy (ART) has been observed over the past decade: at the end of 2015, 16 million people were receiving ART in low- and middleincome countries. However, the emergence of HIV drug resistance (HIVDR) can compromise the effectiveness of antiretroviral drugs, thereby jeopardizing the efficacy of ART to further reduce HIV incidence and HIV-associated morbidity and mortality. HIVDR emerges when HIV replicates in the presence of antiretroviral drugs. If HIVDR becomes widespread, the drugs used to treat HIV infection may become ineffective. To date, levels of HIVDR in countries scaling up ART remain manageable; however, they are slowly increasing. For example, in East Africa, resistance rates to non-nucleoside drugs (such as nevirapine and efavirenz) have recently been reported as above 10%. Although new ART recommendations (“treat all”) and the scale-up of pre-exposure prophylaxis using antiretroviral drugs are likely to further increase levels of HIVDR, concerns about resistant virus should not preclude adoption of a treat-all approach. To minimize the emergence and spread of HIVDR, the World Health Organization (WHO) recommends HIV treatment scale-up be accompanied by measures to monitor and improve the quality of ART delivery and surveillance of HIVDR1,2. At country level, the strategy endorses: 1. country ownership through a. formation of a national HIVDR working group; b. integration of the national HIVDR strategy into the National Strategic HIV Plan; and c. integration of HVDR activities into routine Monitoring and Evaluation function. 2. HIVDR assessments including a. surveillance of HIVDR; and b. annual monitoring of early warning indicators (EWI) of HIVDR 3. leveraging of enablers a. use of WHO-designated laboratory for HIVDR testing; and b. identification and allocation of resources 4. use of all available information to minimize the emergence and transmission of drug-resistant HIV; and 5. timely dissemination of information Recommendations include the following priority assessment activities: 1. monitoring EWI of HIVDR; 2. surveillance of pre-treatment HIV drug resistance (PDR) in populations initiating ART; and 3. surveillance of acquired HIV drug resistance (ADR) in populations receiving ART 3. Due to greater operational complexity, WHO no longer recommends the routine implementation of surveys of transmitted HIVDR among recently infected populations. However, in limited circumstances, if the results will influence a planned public health intervention, surveys of transmitted HIVDR may add value by documenting transmission of drug-resistant virus in specific populations or geographic areas. Countries considering surveillance of transmitted HIVDR are encouraged to contact WHO to discuss its relevance and proposed methodology. This update provides an overview of the essential elements that programme managers should include in programme planning to prevent and monitor the emergence of HIVDR. It also describes programmatic relevance and use of data.
1 Consolidated strategic information guidelines for HIV in the health sector. World Health Organization. World Health Organization, Geneva, Switzerland. 2015. Available at: http://who.int/hiv/pub/guidelines/strategic-information-guidelines/en/ 2 Global Health Sector Strategy on HIV, 2016–2021. World Health Organization. World Health Organization, Geneva, Switzerland. 2016. Available at: http://www.who.int/ hiv/strategy2016-2021/en/ 3 When countries reach optimal coverage of VL testing for routine patient monitoring, remnant VL specimens can be used to inform HIVDR surveillance, if specimens are accessible for genotyping and no major biases are identified.
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MAIN COMPONENTS 1. EWI of HIVDR The first and most important step is to assess whether ART programmes deliver services with the quality required to minimize the emergence of HIVDR. This assessment is achieved through the use of a set of indicators known as “EWI of HIVDR”. These indicators should be integrated into the routine monitoring and evaluation systems of ART programmes. Results should be used to identify gaps in service delivery, for which corrective actions may be taken at the ART clinic or programme level to optimize overall programme performance. EWI monitoring assesses retention on ART, drug supply continuity, adherence to prescribed ART, viral load suppression, and coverage of viral load testing. Standardized definitions and performance targets have been developed for each EWI, along with a colour-based scorecard system, in which “red” signals situations that require corrective action and “green” signals satisfactory performance. It is recommended that EWI be monitored annually at all treatment sites. If this is not feasible, EWI may be monitored through a nationally representative sample of clinics, with the goal to progressively add more clinics in subsequent years until all of them are included. This approach will generate a reliable overview of a national programme’s performance. EWI monitoring should be integrated into routine monitoring and evaluation systems, to minimize costs and strengthen existing data collection and reporting processes.1 If EWI data are not routinely available, the following costs should be taken into account when planning for their abstraction: 1. sensitization of staff at treatment sites to the relevance of measuring performance against a series of standardized indicators, and how these can be used to improve service delivery; 2. organization of data abstraction and data entry (i.e. training and salaries for data abstraction and data entry to ensure high-quality data are obtained); 3. supervisory costs related to data quality assurance (e.g. travel to sites, per diem costs, etc.); 4. data analysis (e.g. data manager, statistician, etc.); and 5. report writing and dissemination, and use of data for clinic and programme optimization. Responsibility for data abstraction can be assigned to existing clinic staff or, alternatively, new staff may be recruited for this task for a limited time. Abstraction costs depend on the number and location of sites, the size of the patient population, whether records are paper- or electronic-based, and ultimately whether abstraction is integrated with other routine monitoring activities. Past experience monitoring EWI suggests that data abstraction in sites working exclusively with paper records
Table 1: Recommended high-priority activities for the surveillance of HIVDR Type of survey PDR Population of interest Individuals initiating ART Outcome measure Nationally representative estimate of HIVDR among individuals about to start ART Nationally representative estimates of viral load suppression and levels /patterns of HIVDR in individuals who have been on ART for 12 (±3) months and/or ≥ 48 months Programmatic relevance Presence of resistance prior to ART initiation can compromise both the therapeutic and prevention benefits of first-line ART. Results inform the choice of drugs to be included in first-line treatment, as well as pre- and postexposure prophylaxis. Recommended periodicity Priority element. To be repeated every 3 years
ADR
Individuals receiving ART for (a) 12 (±3) months and (b) at least 48 months
Viral load suppression is a strong indicator of regimen and Priority element. programme performance. To be repeated every 3 years ADR may compromise the effectiveness of secondand third-line ART, as well as pre- and post-exposure prophylaxis. Adult and paediatric ADR surveys should be conducted separately.
1 The retention, viral load suppression, and drug stock-out indicators are WHOrecommended global indicators to the health sector response. Estimates of viral load coverage and adherence to ART can be measured by data abstraction from routinely recorded information in patient records.
5 may take two to three days per site at an average cost of US$ 500 per clinic. To support EWI implementation, a data abstraction tool can be found at: http://www.who.int/hiv/pub/ meetingreports/ewi_meeting_report/en/. Conducting this survey requires the following: • identification of a representative sample of 15–40 clinics from a list of all clinics initiating ART in the country; and • HIVDR genotypes from patients initiating ART on or after a predefined survey start date. The number of patients to be included in the survey will vary according to a number of factors, such as the number of sites, but will typically fall within the range of 300–500. It is recommended that the duration of patient enrolment be limited to six months to ensure results are available in a timely fashion. Operationally, individuals initiating ART at the selected clinics will be enrolled in the survey regardless of their prior exposure to antiretroviral drugs. However, information on prior antiretroviral drug exposure must be obtained upon enrolment, and will be used at the data analysis stage to distinguish prevalence of HIVDR among initiators with and without prior exposure to antiretroviral drugs. WHO recommends the implementation of PDR surveillance every three years. To estimate the cost of implementing a PDR survey, the following six main budget categories should be considered: 1. protocol development and training; 2. survey coordination; 3. site support visits; 4. laboratory (e.g. cost of genotyping and shipment of specimens); 5. technical support (e.g. protocol adaptation and analysis); and 6. report production, printing and distribution. Assuming a sample size of 460 specimens from 20 sites, and genotyping costs of US$ 150 per specimen, the estimated budget is approximately US$ 240 000 (see Table A1 in the Annex). All figures should be adapted to reflect
2. Surveillance of HIVDR: high-priority activities WHO recommends that countries use the methods listed in Tables 1 and 2 for the surveillance of HIVDR. Table 1 lists high-priority activities and Table 2 lists activities to be considered in specific circumstances. As a matter of national policy, some countries provide routine viral load and HIVDR testing to individuals initiating or failing ART. WHO is currently in the process of developing guidance for these countries on how to use such routinely collected data to inform public health decision-making. Due to greater operational complexity, WHO no longer recommends the routine implementation of surveys of transmitted HIVDR among recently infected populations. However, in limited circumstances, where results are likely to directly influence a planned public health intervention, implementation of these surveys may be warranted. 2
2.1. Surveillance of PDR in populations initiating ART In 2014, WHO and partners developed and published new methods to assess PDR. The WHO-recommended PDR survey method generates a nationally representative prevalence estimate of HIVDR among populations initiating ART. Its main objective is to inform the selection of optimal regimens for first-line treatment and post-exposure prophylaxis (and, when used, pre-exposure prophylaxis).
Table 2: Activities that should be considered in specific circumstances Type of survey HIVDR among infant less than 18 months old Population of interest HIV-positive infant < 18 months old newly diagnosed with HIV and treatmentnaive Outcome measure Programmatic relevance Recommended periodicity Implementation recommended prior to the update of paediatric ART guidelines at the national level Nationally representative Results inform the choice of first- and second- line estimate of HIVDR among paediatric ART regimens infants newly diagnosed with HIV using EID
2 Countries considering implementation of surveys of transmitted HIVDR are encouraged to contact WHO to discuss methodology and anticipated public health action or ART programme actions.
6 the local context and costs. Several laboratories in the HIVResNet network offer genotyping at no or considerably reduced cost. Countries that can use these laboratories can significantly reduce survey costs. A generic concept note for the surveillance of PDR has been developed and is available for country adaptation (http:// www.who.int/hiv/pub/drugresistance/pretreatment_ drugresistance/en/). As well as providing a technical description of the survey method, the concept note addresses various issues related to survey implementation. Separate surveys should be conducted among adult and paediatric populations, as different ART regimens are used in each group. To estimate the cost of an ADR survey, the same budget categories described for the PDR survey should be considered. For the early time point (12 ±3 months) – assuming a sample size of 460 specimens collected from 20 sites, and viral load and genotyping costs of US$ 60 and US$ 150 per specimen, respectively – the generic estimated budget is approximately US$ 205 000 (see Table A2 in the Annex). For the late time point ( ≥ 48 months) – assuming a sample size of 560 specimens from 20 sites, and similar genotyping and viral load costs – the generic estimated budget is around US$ 230 000 (see Table A3 in the Annex). Due to the overlap of certain survey implementation costs (e.g. training, protocol development, on-site supervision), countries are strongly encouraged to include both time points when designing and implementing ADR surveys. This combined approach increases the amount of data collected, while optimizing the use of resources and capacity. The combined implementation of both time points, assuming similar sample sizes obtained from 35 sites, is estimated to cost approximately US$ 335 000 (see Table A4 in the Annex). Further optimization of resources and capacity may be achieved by simultaneous implementation of a survey of PDR and surveys of ADR at both time points. This option provides the maximum amount of information. The combined implementation of a survey of PDR and surveys of ADR at both the 12 (± 3) and 48+ month time points, assuming sampling from a total of 30 sites (20 in operation for 48+ months and 10 in operation for less than 48 months) is estimated to cost approximately US$ 373 300 (see Table A5 in the Annex). All figures should be adapted to reflect the local context and costs. Several designated laboratories within the HIVResNet network offer genotyping at no or considerably reduced cost. Countries that can use these laboratories can significantly reduce survey costs.
2.2 Surveillance of ADR in populations receiving ART The ADR survey methodology is designed to yield nationally representative point prevalence estimates of: 1. programme-level viral load suppression; and 2. the prevalence of HIVDR in populations receiving ART for 12 (±3) months and populations receiving ART for at least 48 months. The level of viral load suppression in a population, as measured in a representative sample of treatment sites, is a strong indicator of regimen and programme performance. The description of resistance patterns in patients failing treatment informs the selection of second-line and potentially third-line regimens. Implementation of an ADR survey requires the following: • identification of a representative sample of 17–40 clinics from a list of all clinics dispensing ART in the country; and • enrolment of consecutive eligible patients who have been receiving ART for a defined time period (e.g. 12 months and/or at least 48 months) on or after a predetermined survey start date. Specimens are obtained from the sampled patients and viral load is assessed. Specimens from individuals with viral loads greater than 1000 copies/ml are subsequently genotyped. The number of patients to be included in the survey will vary according to a number of factors, but should typically fall within the range of 400–600. It is recommended that the duration of patient enrolment be limited to six months to ensure the results are available in a timely fashion. WHO recommends implementing ADR surveillance every three years.
7 A generic concept note for the surveillance of ADR has been developed and is available for country adaptation (http://www.who.int/hiv/pub/drugresistance/acquired_ drugresistance/en/). Similarly to the PDR concept note, it provides a technical description of the survey method and addresses various issues related to survey implementation. relevant in settings where many infants are exposed to or acquire HIV infection. The survey method requires the genotyping of a representative sample of remnant dried blood spots (DBS), collected for paediatric polymerase chain reaction-based HIV diagnosis, and stored at EID laboratories. If possible, all laboratories where EID is performed in the country should participate in the survey and, thus, contribute to the overall sampling. The average sample size is estimated to be approximately 500. Since the survey uses remnant specimens, most implementation costs are related to data entry, specimen shipping and handling, genotyping, technical support for analysis, and report production and distribution. Assuming an average genotype testing cost of US$ 150, the generic estimated survey cost is approximately US$ 140 000 (see Table A6 in the Annex).
3. Surveillance of HIVDR: activities for specific circumstances 3.1 Surveillance of HIVDR among treatment-naive infant less than 18 months old The purpose of this survey is to assess the prevalence of HIVDR among treatment-naive infants younger than 18 months who have been newly diagnosed with HIV using early infant diagnosis (EID). The survey is particularly
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USE OF DATA FOR ART PROGRAMME OPTIMIZATION High-quality treatment programmes are critical to minimizing the emergence of HIVDR. Monitoring EWI of HIVDR and performing surveillance of HIVDR provide countries with evidence that can be used to optimize patient and population-level treatment outcomes.
Surveillance of PDR in populations initiating ART PDR surveys are designed to be repeated every three years, with results providing evidence to support choice of nationally recommended first-line ART regimens and regimens used for pre- and post-exposure prophylaxis. For example, survey results may be used in the analysis of cost effectiveness to inform the pace of change to integrase inhibitor or boosted protease, or use of individual-level PDR testing to guide regimen selection.
EWI of HIVDR EWI monitoring uses scorecarding, which facilitates an at a glance understanding of clinic and programme performance. It also facilitates resource allocation to clinics and identifies the gaps in service delivery that require the most attention. Exploring differences in performance between clinics can lead to documentation and sharing of best practices within countries. This information can be used to allocate resources to the clinics most in need and to address the most pressing gaps in service delivery. EWI monitoring is designed to be implemented annually at all clinics, or to be scaled up in a representative fashion over time. It facilitates a local- and national-level understanding of key factors correlated with treatment optimization and minimization of resistant HIV. Examples of actions that may be taken based on EWI results include: • strengthening of general clinic and pharmacy recordkeeping to facilitate future rounds of reporting; • strengthening of communication and integration between pharmacy and clinic records to identify patients at risk of HIVDR due to missed pill pickups; • engagement of defaulter tracing mechanisms to support retention on ART; • support for and strengthening of supply chain management; and • advocacy for high levels of coverage for viral load testing.
Surveillance of ADR in populations receiving ART ADR surveys support choice of nationally recommended second- and third-line ART regimens. Their implementation, generally contemporaneously with PDR surveys on a rolling three-year cycle, not only provides HIVDR information, but also facilitates trend analysis and allows for nationally representative estimates of retention and viral load suppression.
Surveillance of HIVDR among infants less than 18 months old Although not a high priority, this survey provides results that inform the choice of first- and second-line paediatric regimens. This survey is most useful when implemented prior to national updates of recommended paediatric ART guidelines. Results may be used to support rapid uptake of recommended protease inhibitor-based first-line ART regimens in infants younger than 18 months. Also, by estimating the level of resistance to non-nucleoside reverse transcriptase inhibitor, results will help guide usefulness of these antiretroviral drugs as a component of second- and third-line regimens.
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ANNEX: GENERIC BUDGETS The tables below provide generic estimated budgets for implementing the different surveys of HIVDR described in this document. All figures should be adapted to reflect the local context and costs. All costs are given in US dollars.
Table A1: Estimated budget for PDR surveillance among ART initiators Number of sites: 20 Sample size: 460 Protocol development and training Number of staff per site Transportation costs Per diem cost Number of nights Total
Training of site staff (1 day training) Production of protocol and training materials Survey coordination
2
$200.00
$150.00
1 Subtotal
$14 000.00 $15 000.00 $29 000.00 Total
Number of staff
Cost per staff/ month
Number of months
Number of sites
Site coordination Nurse incentive National coordination Data manager Site support visits
1 2 1 1
$300.00 $50.00 $1,000.00 $800.00
8 8 8 6
20 20 1 1 Subtotal
$48 000.00 $16 000.00 $8 000.00 $4 800.00 $76 800.00 Total
Study coordinator and driver Fuel Air tickets to remote sites Local transportation Laboratory
Note: 2 days per visit, USD 50 per diem, 2 visits Note: for six months Note: 5 flights, USD 200 each Subtotal Per unit
$8 000.00 $2 000.00 $1 000.00 $1 000.00 $12 000.00 Total
Blood collection DBS preparation and storage Genotyping Laboratory labor cost for genotyping Shipment of specimens Technical support
$3.00 $5.00 $150.00 Note: US$ 100 per site for national shipping, US$ 250 for international Subtotal
$1 380.00 $2 300.00 $69 000.00 $2 500.00 $2 250.00 $77 430.00 Total
Consultant (US$ 500 daily fee, US$ 200 per diem, 14 days) and flight Statistical support for analysis and interpretation Subtotal
$1 800.00 $10 000.00 $22 800.00 Total
Report production, printing and distribution
Report production and distribution Workshop to dicuss policy implication and actions required (15 outside participants, 15 local) Subtotal
$10 000.00 $10 500.00 $20 500.00 $238 530.00 TOTAL
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Table A2: Generic budget for ADR surveillance (12-month time point) Number of sites: 20 Sample size (12 months): 460 Estimated % with VL>1000 (12 months): 5% 12(±3) months Protocol development and training Number of staff per site Transportation costs Per diem cost Number of nights Total
Training of site staff (1 day training) Production of protocol and training materials Survey coordination
2
$200.00
$150.00
1
$14 000.00 $15 000.00 Total
Number of staff
Cost per staff/ month
Number of months
Number of sites
Site coordination Nurse incentive National coordination Data manager Site support visits
1 2 1 1
$300.00 $50.00 $1 000.00 $800.00
8 8 8 4
20 20 1 1
$48 000.00 $16 000.00 $8 000.00 $3 200.00 Total
Study coordinator and driver Fuel Air tickets to remote sites Local transportation Laboratory
Note: 2 days per visit, US$ 50 per diem, 2 visits Note: for 6 months Note: 5 flights, US$ 200 each
$8 000.00 $2 000.00 $1 000.00 $1 000.00 Per unit Total
Blood collection $3.00 DBS preparation and storage $5.00 VL $60.00 Genotyping $150.00 Laboratory labor cost for genotyping and VL Note: US$ 100 per site for national shipping, US$ 250 for international Shipment of specimens Technical support
$1 380.00 $2 300.00 $27 600.00 $10 350.00 $2 500.00 $2 250.00 Total
Consultant (US$ 500 daily fee, US$ 200 per diem, 14 days) and flight Statistical Suppport for analysis and interpretation Report production, printing and distribution
$12 800.00 $10 000.00 Total
Report production and distribution Workshop to dicuss policy implication and actions required (15 outside participants, 15 local) TOTAL VL: viral load
$10 000.00 $10 500.00 $205 880.00
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Table A3: Generic budget for ADR surveillance (48+ month time point) Number of sites: 20 Sample size (48+ months): 560 Estimated % with VL>1000 (48+ months): 30% 48+ months Protocol development and training Number of staff per site Transportation costs Per diem cost Number of nights Total
Training of site staff (1 day training) Production of protocol and training materials Survey coordination
2
$200.00
$150.00
1
$14 000.00 $15 000.00 Total
Number of staff
Cost per staff/ month
Number of months
Number of sites
Site coordination Nurse incentive National coordination Data manager Site support visits
1 2 1 1
$300.00 $50.00 $1 000.00 $800.00
8 8 8 4
20 20 1 1
$48 000.00 $16 000.00 $8 000.00 $3 200.00 Total
Study coordinator and driver Fuel Air tickets to remote sites Local transportation Laboratory
Note: 2 days per visit, US$ 50 per diem, 2 visits Note: for six months Note: 5 flights, US$ 200 each
$8 000.00 $2 000.00 $1 000.00 $1 000.00 Per unit Total
Blood collection $3.00 DBS preparation and storage $5.00 VL $60.00 Genotyping $150.00 Laboratory labour cost for genotyping and VL Note: US$ 100 per site for national shipping, US$ 250 for international Shipment of specimens Technical support
$1 680.00 $2 800.00 $33 600.00 $25 200.00 $2 500.00 $2 250.00 Total
Consultant (US$ 500 daily fee, US$ 200 per diem, 14 days) and flight Statistical support for analysis and interpretation Report production, printing and distribution
$12 800.00 $10 000.00 Total
Report production and distribution Workshop to discuss policy implication and actions required (15 outside participants, 15 local) TOTAL VL: viral load
$10 000.00 $10 500.00 $227 530.00
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Table A4: Generic budget for ADR surveillance (combined 12 month and 48+ month time point) Number of sites: 35 Sample size (12 months): 460 Sample size (48+ months): 560 Estimated % with VL>1000 (12 months): 15% Estimated % with VL>1000 (48+ months): 30% Shared survey costs Protocol development and training Number of Transportation staff per site costs Per diem cost Number of nights Total
12(±3) months
48+ months
Training of site staff 2 (1 day training) Production of protocol and training materials Survey coordination Number of staff
$200.00
$150.00
1
$24 500.00 $15 000.00
Cost per staff/month
Number of months
Number of sites
Total
Site coordination Nurse incentive National coordination Data manager Site support visits
1 2 1 1
$300.00 $50.00 $1 000.00 $800.00
8 8 8 4
35 35 1 1
$84 000.00 $28 000.00 $8 000.00 $3 200.00 Total
Study coordinator and driver Fuel Air tickets to remote sites Local transportation Laboratory
Note: 2 days per visit, US$ 50 per diem, 2 visits Note: for 6 months Note: 5 flights, US$ 200 each
$14 000.00 $2 000.00 $1 000.00 $1 000.00 Per unit Total
Blood collection DBS preparation and storage VL Genotyping Laboratory labor cost for genotyping and VL Shipment of specimens Technical support
$3.00 $5.00 $60.00 $150.00 $4 000.00 $250.00 Total
$1 380.00 $2 300.00 $27 600.00 $10 350.00 $1 500.00
$1 680.00 $2 800.00 $33 600.00 $25 200.00 $2 000.00
Consultant (US$ 500 daily fee, US$ 200 per diem, 14 days) and flight Statistical Suppport for analysis and interpretation Report production, printing and distribution
$12 800.00 $10 000.00 Total
Report production and distribution Workshop to dicuss policy implication and actions required
$10 000.00 $10 500.00 Subtotal $228 250.00 $43 130.00 $65 280.00 Grand Total $336 660.00
VL: viral load
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Table A5: Generic budget for combined PDR and ADR surveillance Number of “old” sites (sites in operation for more than 48+ months): 50 Number of “new” sites (sites in operation for less than 48 months): 20 Example: 10 000 people on ART at “old” sites and 5 000 people on ART at “new” sites Total number of sites sampled: 20 “old sites” and 10 “new” sites (total 30 sites) Sample size (PDR): 410 Sample size (12 ± 3 months): 420 Sample size (48+ months): 520 Estimated % with VL>1000 (12 months): 15% Estimated % with VL>1000 (48+ months): 30% Shared survey costs Protocol development and training Number of Transportation staff per site costs Per diem cost Number of nights Total
PDR
12(±3) months
48+ months
Training of site staff 2 $200.00 (1 day training) Production of protocol and training materials Survey coordination Number of staff Cost per staff/month
$150.00
1
$21 000.00 $15 000.00
Number of months
Number of sites
Total
Site coordination Nurse incentive National coordination Data manager Site support visits
1 2 1 1
$300.00 $50.00 $1 000.00 $800.00
8 8 8 4
30 30 1 1
$72 000.00 $24 000.00 $8 000.00 $3 200.00 Total
Study coordinator and driver Fuel Air tickets to remote sites Local transportation Laboratory
Note: 2 days per visit, US$ 50 per diem, 2 visits Note: for 6 months Note: 5 flights, US$ 200 each
$12 000.00 $2 000.00 $1 000.00 $1 000.00
Per unit
Total
Blood collection $3.00 DBS preparation and storage $5.00 VL $60.00 Genotyping $150.00 Laboratory labor cost for genotyping and VL Shipment of Note: US$ 100 per site for national shipping, US$ 250 for intl specimens Technical support
$1 230.00 $2 050.00 $61 500.00 $4 000.00 $250.00 Total
$1 260.00 $2 100.00 $25 200.00 $9 450.00 $3 000.00
$1 560.00 $2 600.00 $31 200.00 $23 400.00 $2 000.00
$1 500.00
Consultant (US$ 500 daily fee, US$ 200 per diem, 14 days) and flight Statistical Suppport for analysis and interpretation Report production, printing and distribution
$12 800.00 $10 000.00 Total
Report production and distribution Workshop to dicuss policy implication and actions required VL: viral load
$10 000.00 $10 500.00 Subtotal $206 750.00 $64 780.00 Grand Total
$41 010.00
$60 760.00 $373 300.00
14
Table A6: Generic budget for surveillance of HIVDR among treatment-naive infants less than 18 months old Number of participating labs: 10 Sample size: 500 Protocol development and training Total
Production of protocol and training materials Training of site staff (1 day training) Subtotal
$10 000.00 $14 000.00 $24 000.00 Total
Laboratory Per unit
Genotyping Laboratory labor cost for genotyping Shipment of specimens Technical support
$150.00 $250.00 $100.00 Subtotal
$75 000.00 $2 500.00 $1 250.00 $78 750.00 Total
Consultant (US$ 500 daily fee, US$ 200 per diem, 14 days) and flight Statistical support for data analysis and interpretation Subtotal
$12 800.00 $10 000.00 $22 800.00 Total
Report production, printing and distribution
Report production and distribution Workshop to dicuss policy implication and actions required Subtotal
$10 000.00 $4 000.00 $14 000.00 $139 550.00 TOTAL
For more information, contact: World Health Organization Department of HIV/AIDS 20, avenue Appia 1211 Geneva 27 Switzerland E-mail: hiv-aids@who.int www.who.int/hiv
ISBN 978 92 4 151009 7