Hivdr prevention and Assessment Annual Country Report Outline

A. Activities and Results

1. 
   For pilot year, describe process of protocol adaptation from WHO generic protocol
   

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  Include names and affiliations of responsible individuals
  
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  State date of ethical clearance
  

2. 
   Describe process of selection for pilot sites
   

1. 
   Describe specimen type (baseline and endpoint), collection procedures, and transport procedures. List specimen tracking variables used in survey
   
2. 
   Describe the patient, specimen, and data flow at each site and how survey procedures are integrated into these.
   
3. 
   In an appendix, list patient variables (baseline and endpoint) from monitoring site-baseline. These variables should all be "required" variables at the country level; they should be selected from the WHO list of required and optional variables [See Appendix 4], and may also include additional variables. Describe data collection process from the medical records and other sources; state who performed the data collection.
   
4. 
   List the baseline and endpoint site variables collected, including process for their collection [See Appendix 4.]
   

3. 
   Describe the enrolment and data collection process; who enrolled patients, consent process, who extracted data and when. Additionally describe,
   

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  Specimen handling processing and tracking
  
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  Transport of and storage of specimens
  
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  List specimen processing lab(s) and viral load laboratory
  
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  List WHO-accredited laboratory(ies) performed genotyping?  Describe methods briefly.
  
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  Quality assurance and validation process
  

Categorizing HIVDR

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  Viral suppression: For the purposes of HIVDR Monitoring, viral suppression is defined as an HIV RNA <1,000 copies/mL on viral load testing.
  
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  HIV drug resistance: HIV drug resistance is considered the presence of one or more major mutations as defined by the Stanford HIVDR database.
  
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  Potential HIV drug resistance: Specimens with a viral load > 1,000 copies/mL, if drawn at endpoint (that is, from individuals still on their first-line regimen 12 months after starting ART, or still on their first line ART regimen before switch to a second line regimen), are classified as having potential drug resistance. Individuals who have been lost to follow-up or who stopped ART within the first 12 months of ART, and from whom no specimens are available for classification, are also classified as having potential HIV drug resistance. This definition is only used in classifying an endpoint outcome result.
  

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  HIV drug resistance prevention: For the purposes of HIVDR monitoring, HIV drug resistance prevention is defined as a specimen with an HIV RNA <1,000 copies/mL on viral load testing, drawn from an individual still on first line ART either before switch to a second line regimen, or at the 12 months follow-up after initiating ART.
  

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  HIVDR not evaluated: Individuals whose endpoint is transfer out or death are not relevant to the evaluation of HIVDR prevention at the sentinel clinic. (They are therefore removed from the numerator and denominator before the estimation of HIVDR prevention prevalence in the first year of ART.)
  

Results/Analyses

Baseline factors

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  Proportion with reported previous ARV experience (Subcategories: Overall, PMTCT, informal experience)
  
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    The overall proportion with any type of previous ARV experience will be calculated using as the numerator individuals with any type of previous ARV exposure and using as the denominator the total number of monitoring participants at baseline.
    
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    The proportion of female sentinel monitoring participants at baseline with PMTCT exposure will be calculated using as the numerator the number of women with PMTCT experience and using as the denominator the total number of women participating in sentinel monitoring.
    
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    The proportion of individuals with other informal ARV experience will be calculated using as the numerator the number of individuals with informal ARV experiences and as the denominator the total number of monitoring participants at baseline.
    

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  The proportion of individuals with one of more major HIVDR mutations as defined by the Stanford HIVDR database will be calculated at baseline using as the numerator individuals with one or more HIVDR mutation at baseline and using as the denominator the total number of monitoring participants at baseline. This proportion is definite HIVDR at baseline. The proportion of the population with HIVDR. Appropriate sub-analyses will be performed to calculate the proportion with HIVDR by specific mutation, mutation pattern and by specific ARV drug and drug class.
  
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  The proportion of the population with Potential HIVDR at baseline will be calculated using as the numerator the number of individuals with history of ARV experience (PMTCT, informal, other) who have no HIVDR mutations detected (i.e. “wild type” virus) at baseline and using as the denominator the total number of monitoring participants at baseline. Subcategory analyses will be performed to include overall HIVDR, specific drug class, specific drugs, and specific mutations of interest.
  
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  The proportion of individuals prescribed standard first-line ART regimens according to national guidelines at baseline will be calculated using as the numerator the total number of individuals commencing ART who are prescribed a standard first-line regimen according to national guidelines and using as the denominator the total number of individuals commencing ART at baseline.
  

2 X 2 analyses will be performed to evaluate univariate associations between relevant demographic factors and the elements described above. Additional analyses will be performed to assess for association between previous ARV experience and the major endpoint HIVDR outcomes described in Section 2-2.5.

Endpoint program factors

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  Proportions of patients who reach various levels of on-time ARV drug pick-up will be calculated.
  

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  Classify participants as reaching the following levels of on-time drug pick-up: <50%, 50%-59%, 60%-69%, 70%-79%, 80%-89%, > 90%. (Subsets of these categories may also be calculated if these do not reflect particular country targets.) To classify each participant whose outcome is not "dead" or "transferred out" into one of the on-time drug pick-up categories, record as the numerator the number of on-time drug pick-ups (that is, pick-ups performed before the previously picked-up prescription would have run out) made between baseline and endpoint and record as the denominator the number of "required" drug pick-ups (this number should be based on the dates calculated for pick-up based on when previously picked-up drugs would have run out) for each individual between baseline and endpoint. Divide the numerator by the denominator and multiply by 100 to calculate the percentage of on-time appointments kept by the individual. Place the individual's HIVDR-MID and the percentage into the appropriate column.
  

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  Proportions of patients reporting various levels of adherence as reflected by the VAS 30-day adherence question will be calculated for participants reaching defined endpoints (switch and on ART at 12 months)..
  

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  Classify participants as reporting the following levels of adherence: <50%, 50%-59%, 60%-69%, 70%-79%, 80%-89%, > 90%. (Subsets of these categories may also be calculated if these do not reflect particular country targets. However, analysts should be aware that the latest comprehensive review of evidence shows that previous reports that > 95% adherence is required to prevent HIVDR emergence were based on studies of unboosted protease inhibitor regimens. Bangsberg summarizes the current evidence on regimens consisting of 2 NRTIs + 1 NNRTI by stating that 70% - 80% adherence is likely to be sufficient to prevent the emergence of resistance.
  

It is also recommended that this analysis be performed separately for those with the two respective outcomes ("Switch" or "On first-line ART at 12 months")

Endpoint outcome measures

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  HIVDR prevention: The proportion of individuals in the cohort achieving HIVDR prevention and who are on ART at 12 months will be estimated by HIV viral load testing.
  
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    To calculate the proportion of individuals achieving HIVDR prevention on first-line ART at 12 months the numerator is the number of participants with HIV viral load <1,000 copies/ml at 12 months. The denominator is the total number of individuals in the cohort who commenced ART at baseline minus deaths and “transfers out”.
    
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      Numerator = Number of individuals with viral load suppression at 12 months (viral load suppression = prevention of HIVDR)
      

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  Potential premature switch The proportion of the population with apparent HIVDR prevention at the time of switch from first- to second-line regimens will be estimated by HIV viral load testing.
  
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    To calculate the proportion of individuals achieving HIVDR prevention on first-line ART at switch the numerator is the number of participants with HIV viral load <1,000 copies/ml²⁶ at switch. The denominator is the total number of individuals in the cohort who have switch as an endpoint .
    

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  Potential HIVDR:
  
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    Participants who are lost to follow-up or stop and for whom no specimens are available at endpoint are classified as having potential HIVDR. Include all participants with these endpoints in the numerator and denominator for each of these categories. (That is, 100% are categorized as having potential HIVDR in each of these categories. Additional analyses may also be reported in which some proportion of these individuals are categorized differently, but the initial analysis should be based on the assumption of potential HIVDR.)
    
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    For participants reaching the endpoints On ART at 12 months or Switch) include in the potential HIVDR numerator participants with HIV viral loads >1,000 copies/ml²⁶ at endpoint without HIVDR mutations seen on genotypic testing, or for whom no specimen was available. A separate calculation of those with potential HIVDR in each of these categories is made initially; the denominator for each of these calculations is the number categorized with each respective endpoint.
    
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    For the overall categorization of Potential HIVDR for the survey, add the numbers of participants with potential HIVDR in each of the numerators listed above. The denominator should include all participants whose outcome is not "dead" or transferred out.
    

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  HIVDR: The proportion of the population with HIVDR at the endpoint s on ART at 12 months and switch will be calculated first, and then the percentage of all participants with HIVDR categorized with an analyzable endpoint.
  

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  To calculate the proportion of the population with HIVDR at 12 months the numerator is the number of individuals on ART at 12 months with one or more HIVDR mutations detected on genotypic testing and with an HIV viral load >1,000 copies/mL²⁶, and the denominator is the number of participants on ART at 12 months. ,
  
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  To calculate the proportion of the population with HIVDR at switch the numerator is the number of individuals who switch and have one or more HIVDR mutations detected on genotypic testing and with an HIV RNA >1,000 copies/mL²⁶. The denominator is the total number of individuals who switch during the monitoring period.
  
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  To calculate the proportion with HIVDR at endpoint, add the numerators of participants with HIVDR from the categories Switch and on ART at 12 months. The denominator should include all participants whose outcome is not "dead" or transferred out.
  

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  Specific mutations and mutation patterns among monitoring participants not achieving viral suppression at 12 months or at time of switch will be aggregated and described by specific mutation, mutation pattern and by drug and drug class. Mutations will be determined based upon the WHO HIVDR accepted standard mutation list (Appendix 3).
  

6. Describe feasibility of ongoing HIVDR monitoring surveys in country and describe challenges, lessons learned, and changes to plans based on current year survey

Select representative ART sites with at least 100-130 patients starting ART over 3-6 months (or longer only if necessary, but no longer than one year).

Describe principles of site selection used in the in-country adaptation of generic monitoring protocol: (grid with relevant characteristics or another method). Rolling three-year cycle of 15-30 ART sites (5-10 per year).

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  Year One: List pilot sites
  
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  Year Two: List 5-10 additional sites.
  
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  Year Three: List 5-10 additional sites
  
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  Year Four: the Year One pilot sites plus additional sites
  
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  Year Five: Year Two sites (plus other sites if needed)