# Presentation: 037614

## Specific HIV Testing ApplicationsChallenges and Choices

**Mark A. Rayfield, Ph.D.**
*Division of  GAP*
*National Center for HIV, STD, and TB Prevention*
*Centers for Disease Control and Prevention*

## Key Elements

**Spectrum of Tools**
**Right Tool for Task**
**Specimen is Central**

## Challenges

**Too narrow assessment of needs**
**Limited testing and algorithm options**
**Failure to establish EQA for gold standards**
**Lack of recognized authority or responsibility among laboratory elements**
**Failure to establish national testing policies**

## Centralized Testing

**Ease of management and Quality Assurance**
**Advanced technologies & efficiency of scale**
**Ease of data management**
**Limited dissemination of technologies**
**Emphasized logistics of specimen transfer**

## Decentralized Testing

**Disseminated technologies**
**Local involvement & consensus building**
**Improved integrated surveillance systems**
**Expanded QA effort – decentralized**
**Need for improved data management and logistical support**
**Heightened concerns for confidentiality **

## Passive Surveillance

**Case based reporting**
**Decentralized multi-tiered testing**
**Single testing application ****- diagnostic**
**Multiple testing algorithms**
**Requires unified testing strategy**
**Multi-tiered referral and quality systems approach **

## Passive Surveillance

***HIV lab networks in China***

## Surveillance of General Population

**General population ****– household based****- linked biological markers****- consented, decentralized testing**
**Representative population - ****uniformed recruits, ANC ****- unlinked , anonymous testing****- centralized or decentralized testing**
**Multiple testing applications****- counseling and testing****- unlinked specimen testing**

## Algorithms

** ****Single / multiple EIA** 	**- select for optimal sensitivity and specificity****	****- choice of confirmation**** **
** ****Multiple simple / rapid tests **	**- loss of efficiency of scale****	****- expanded access to sentinel  populations**** **
** ****Combinations of EIA and rapid test; order of application**	**- decentralized: simple / rapid -> EIA****	****- centralized: EIA -> simple /  rapid**

## Targeted Populations“At Risk”

**Sentinel, “at risk” populations****- hard to reach**** ****populations**
**Decentralized, consented testing****- on site sampling with regional testing****- on site individual testing and counseling**
**Occasionally, unlinked testing of excess materials****- STD clinics, troop deployments****- VCT referrals **

## Determine HIV 1/2

|  | GSPositive | GSNegative | Total |
| --- | --- | --- | --- |
| Determine Positive | 358 | 1 | 359 |
| Determine Negative | 2 | 611 | 613 |
| Total | 360 | 612 | 972 |

**Gold Standard = Double EIA + Western blot**
**Sensitivity = 358 / 360 = ****99.44%**
**Specificity = 611 / 612 = ****99.84%**
**           ****PPV =358 / 359 = ****99.72%**
**           ****NPV= 611/ 613 = ****99.67%**

## Dried Blood Spot Testing

**Optimization of assay protocols for DBS**
**Standardized elution protocols**
**Development Internal Assay Controls****	****- off-label use of diagnostics****	****- regional production of panels**
** ****Development of Transport Controls****	**** ****- regional production**
**Standardized Training**** ****	****- regional workshops****	****- country specific needs**

## On-site Rapid Test Performance Data vs. DBS Reference Serology

**Sens**

-  %

**Spec**

- %

**PPV**

- %

**NPV**

- %

**Eff**

- %

**Determine**

- N=

- 863

- 9

- 7.8

- 97.

- 4

- 8

- 4

- .

- 8

- 99.

- 7

- 97.

- 9

**Hema**

**-**

**Strip**

** **

- N=

- 688

- 98.5

- 99.

- 4

- 94.

- 2

- 99.8

- 99.

- 3

**HIV**

**-**

**Chek**

** **

- N=134

- 95.0

- 97.4

- 86.4

- 99.1

- 97.0

## Guidance

- FDA approval list- **may not be appropriate to need****- driven by manufacturer’s submittals**
- WHO bulk procurement list (reports)**- not validated in intended use environment****- dated**
- USAID waiver lists**- procurement document****- validated algorithm in intended use enviroment**

## WHO ReportsOperational Characteristics of Commercially Available Assays

**Ongoing process initiated in 1989** 	**Blood Safety Unit of WHO**	**Institute of Tropical Medicine, Antwerp, Belgium**
**Relevant reports 9/10/11/12/13**** ****(EIA & rapid tests)****	****Whole Blood, Serum, Plasma, Oral Fluids, Urine**
**Multiple evaluation panels**** ****(sera & seroconversion)****	****Africa (192), Asia (99), Europe (206), Latin America (98)**
**Desired Characteristics****	****high level of sensitivity and specificity****	****long shelf-life at ambient temperatures****	****reasonable costs****	****ease of use**

## Critical ElementsWHO Reports

**Sensitivity & Specificity**  **(95% CL)**
**Positive & Negative Predictive Values**
**Delta Value****	****- efficacy in separating pos./neg. samples from cut-off**
**Reproducibility**
**Inter-reader variability**
**Time interval for early detection of seroconversion**** **

## Training

***Methodologies***

***Guidelines  for best practices******- consensus ******- broad audience***

*Training*

## Quality control and assurance issues

**Specimen collection and transport**
**Standard operating procedures**
**Personnel qualifications**
**Proficiency testing**
**Instrument and reagent checks**
**Record keeping/Reporting**
**Preanalytic, analytic, and****	****postanalytic checks**

## Future Directions

**Future Directions**

**Incidence Assays**	**- DBS**
**	****- Rapid Tests**
**Oral Fluids**	**-Sputum samples**
**DBS Molecular Surveillance**	**- Infant PCR****	****- Resistance****	****- Genotyping**

## Coordinated Process

**Coordinated Process**

**Policy**

**Performance**

** ****Application**

**Training**