# Presentation: 037617

## Technical solutions to program questions- HIV Testing StrategiesTechnical issues

**Mark A. Rayfield, Ph.D.**
**Assoc. Director for Global Science**
**Division of  AIDS, STD, and TB Laboratory Research**
**National Center for Infectious Diseases**

## Atlanta’s on Venus ...the Mission’s on Mars

***...******the transition from research to practice ...***

## Frequently Expressed Needs

**Strengthening laboratory capacity **
**Prevention of mother-to-child transmission **
**Voluntary counseling and testing**
**Surveillance **
**Training**

## Common Requests

**PCR**- real time - multiplex
**Viral load**
**CD4 count / monitoring**
**Resistance monitoring**
**Decentralized testing**- dried blood spots- rapid tests
**Incidence assays**

## Laboratory Assessment

**Limited decentralization**
**Weak NRL or no NRL**
**Resource Poor **
**Aging Professional Staff**
**Weak QA and no EQA**
**Poorly integrated services**
**Limited exchange of data**

## Integrated Laboratory Activities

**Surveillance**** ****- HIV, STI, and TB surveys and case reporting****  - Integrated Disease Surveillance**
**Laboratory support to Programs **
**Points of Service**** ****- VCT, Antenatal, and Community Health Clinics**
**Multidisciplinary Referral Labs**** ****- Soft funding for project specific research**

## Consensus Building

**Surveillance strategies****	****- strengthening information systems****	****- consensus on methodologies**
**Development of reference laboratories **
**Evaluation of diagnostic programs ****	****- syndromic management of STIs****	****- simple/rapid HIV testing algorithms****	****- microscopy**
**Blood safety programs**
**Monitoring of resistance & treatment failure**
**Monitoring of disease progression**

## National

**Policy and Strategic Planning**

**Integrated Services and Testing**

**National**
**Provincial**
**District**
**Community**

## Common Requirements

**National Standards of Training****- technician / supervisor****- test performer****- community health care worker**
**Quality Assurance****- EQA (National – Provincial – District)****- Provincial / District Quality Assurance Package****- Proficiency testing & observed performance**
**Constant Reagent Supply**
**Guidance for Standard Operating Procedures**

## Standardized 

***Standardized ***
***Methodologies***

## Integrated Lab ServicesTargeted Formats

**Community Health Clinic****- confidential / shared ****- two test HIV algorithm with counseling and follow-up****- HIV, Syphilis,  Urine, and Blood smears**
**Antenatal Clinics****- confidential / shared ****- two test algorithm with follow-up****- HIV, Syphilis, Urine, Blood smears and basic typing**
**Voluntary Counseling and Testing Centers** **- Anonymous  /  stand alone ****- three test algorithm with referral****- HIV and Syphilis**

## I’m going to do unlinked survey of 40,000 people involving decentralized testing with simple/rapid tests

***... ******the tests chosen require refrigeration***

***We’re going to base our survey in ANC sites which ******routinely do RPR and TPHA assays – so we have a ***
***source of  unlinked excess blood***
***... ******many sites have intermittent electricity, some none***

## WHO/UNAIDS

** ****HIV testing strategy II**

**Assay 1 (A1)**

**Sample**

**Assay 2 (A2)**

** ****Negative**

**-**

**+**

**-**

**+**

** ****Positive**

**Repeat**
**A1**** ****and**** ****A2**

**A1****- / ****A2 ****-**
**Negative**

**A1****+**** ****/****A2 ****- ****;**** ****A1****- /****A2****+**
**  ****Indeterminate**

**A1****+/ ****A2****+**
**Positive**

## Sample

**Assay 2 (A2)**

** ****Negative**

**-**

**+**

**-**

**+**

**Assay 1 (A1)**

**Sample**

**Sample**

**-**

**+**

**Assay 3 (A3)**

**A1****+ / ****A2****- / ****A3****-**
**Negative**

**A1****+ / ****A2****- / ****A3****+**
**Positive**

***-***

**+**

**+**

**-**

## Priorities for Use of Rapid Tests

**Programmatic priorities include: ****VCT****,**** MTCT**** , differential diagnosis, clinical assessment, ****rural blood services****,  and emergencies.**** **
**Technical considerations include: need for rapid results, ****elimination of cold chain**** for both reagents and specimens, cost effectiveness in low volume labs, and ****simplicity of testing****.**

## TIMELINE

***            ***
***    ******	****	**	**	**      ****Phase I****	**	**       ****Phase II**** **	**	**       ****Phase III***
-               		**(~ 3 months)**		 **(3-6 months)** 		      **(6 months)**	     **(> 3 months)**
- 	**Determine Capacity**
- 	**Literature Review**
- 	**Situation Analysis**
- 	**Needs Analysis**                **Proposal**
- 		                    **Ethical Review**     **Establish Panels**
- 		                    **Procurement****	****     Evaluation **
**	****	****                  ****Training****	****     Analysis of Data ****	****    Site Selection**
**	****	****	****     ****Algorithm Decision****	****    Training of Staff**
**	****	****	****     ****Publish Findings****	****    On Site Evaluation**
**	****	****	****	****	****	****    ****Algorithm Approval****	****	**
**	****	****	****	****	****	****	****	****      ****Pilot Manuals**
**	****	****	****	****	****	****	****	****      ****Monitor Performance**
**	****	****	****	****	****	****	****	****      ****Publish Algorithm**

-   **Project Development         Test Evaluation / Algorithm  Development           Monitoring**
** **

**TIMELINE**

## Advantages

**Predetermined  serostatus **
**Pre-selected evaluation panel**
**Limits excess testing**
**Avoids major changes to lab workload**
**Multiple tests run simultaneously**
**Shortened evaluation period**** **

***Pre-evaluation***

***Phase I***

**Serum Repository Established**
**	****(500 sera)**

**Validation on Specimen of Choice**

**Propose Algorithm**

**Selection of Pilot Sites**

**Validate Algorithm**

***Phase II***

***Strategy I***

**Disadvantages**
**Specimen storage maybe sub-optimal**
**Differential test performance**
**Requires validation with whole blood**
**Additional  QA measures**
**Potential need to re-determine serostatus **

## Evaluation Methods

**Study Sites = City A and City B**
**Raw dataset = 1022 records****	**
**Final Panel  = 972 specimens (360 positives / 612 negatives)**

## Advantages

**Does not require established serum bank**
**Use of fresh sera**
**Concurrent determination of serostatus**
**Early determination of poor performance**

***Phase II***

***Strategy II***

***Phase I***

**Validation on Specimen of Choice**

**Propose Algorithm**

**Selection of Pilot Sites**

**Validate Algorithm**

***POS***

***NRL***

***NRL***

***POS***

***POS***

***Extended POS***

**Establish Sero-Status**

**Disadvantages**
**Low prevalence -> excess testing **
**Increased evaluation time in Phase I**
**Differential test performance**
**Further validation with whole blood needed**

## Increase in Demand for VCTSame Day Results

## Advantages

**Does not require established serum bank**
**Immediate validation of specimen of choice**
**Concurrent determination of serostatus**
**Early determination of poor performance**
**Early assessment of testing venue**
**Disadvantages**
**Low prevalence -> excess testing **
**Increased evaluation time in Phase I**
**Logistical difficulties increase**
**Limited specimen size and volume**
**Multiple specimen formats required**

***Phase I***

**Propose Algorithm**

**Selection of Pilot Sites**

**Validate Algorithm**

***Phase III***

***NRL***

***POS***

***Extended POS***

**Establish**
**Sero-Status**

***Phase II***

***Strategy III***

**Rapid Test**
**Evaluation**
**(Whole Blood)**

***NRL***

***POS***

**Panel **
**Selection**

***POS***

## TIMELINE

**TIMELINE**

## Comparison of Rapid Testing ELISA Reference Labs