# Presentation: 714739

## Module 4:  HIV Testing Strategies and Algorithms 

## Learning Objectives

- At the end of this module, you will be able to:
- Discuss the process for developing a national testing algorithm
- Explain how sensitivity, specificity, positive/negative predictive value relate to development of an HIV rapid testing algorithm
- Explain the HIV rapid testing algorithm approved in your country
- Determine HIV status following a particular algorithm

## Content Overview

- Testing strategies and algorithms
- Developing national testing algorithm
- Measuring performance of  HIV rapid tests
- Interpreting HIV status

## Strategies and Algorithms

- Strategies – Testing approach used to meet a specific need, such as:
- Blood Safety
- Surveillance
- Diagnosis
- Algorithms – The combination and sequence of specific tests used in a given strategy

## For a given strategy, multiple algorithms may  be used depending on the needs of testing settings
The number of algorithms should be limited 

- The number of algorithms should be limited

**Strategies and Algorithms (Cont.)**

## HIV Testing Strategies

-  Parallel testing
- Samples are tested simultaneously by two different tests
-  Serial testing
- Samples tested by a first test
- Result of first test determines whether additional testing is required

## Testing Algorithms Should be Developed at National Level

**Key Steps :**
- Identify appropriate tests
- Develop algorithm
- Build consensus
- Develop policy
- Bring into national scale
- Review testing algorithms annually

**Notes:**
There are multiple tests marketed and available & multiple testing strategies.  Each country must identify the appropriate tests for used within given environment

Need standardardized approach to algorithm-  Not all testing strategies are appropriate for a given environment...not one size fits all

## Timeline for Developing National Testing Algorithm

**Timeline for Developing National Testing Algorithm**

## Advantages of National Testing Strategies and Algorithms

- Facilitates:
- Country-level standardization
- Procurement and supply management
- Training
- Quality assurance

## Key Factors in Determining a Country’s Algorithm

- Test performance in country
- Test availability in country
- Program needs
- Ease of use
- Type of specimen
- Cost
- Potential need to differentiate between HIV 1 & HIV 2

## Evaluating Test Performance: Basic Terms

**Sensitivity (Se)** of a test is its capacity to correctly identify people that are infected with HIV.
**Specificity (Sp) **of a test is its capacity to correctly identify people that are not infected with HIV.
**Positive Predictive Value (PPV**) is the probability that a person who tests reactive is indeed infected with HIV.
**Negative Predictive Value (NPV)** is the probability that a person who tests negative is not infected with HIV.

## Calculating Sensitivity, Specificity, PPV, & NPV

**B+D**

**A+C**

**Total**

**C+D**

**D**

**C**

**Negative**

**A+B**

**B**

**A**

**Positive**

**Total**

**HIV -uninfected**

**Actual HIV status (Gold Standard)**

- Test
- result

**HIV ****infected**

**Sensitivity = A  ÷ (A+C)**
**Specificity = D  ÷  (B+D)**
**Positive Predictive Value = A ÷ (A+B)**
**Negative Predictive Value** **=  D ÷ (C+D)**

## Calculating Sensitivity, Specificity, PPV, & NPV (Cont’d)

**1000**

**B+D (626)**

**A+C (374)**

**Total**

**C+D(628)**

**D (624)**

**C (4)**

**Negative**

**A+B(372)**

**B (2)**

**A (370)**

**Positive**

**Total**

**HIV -uninfected**

**Actual HIV status (Gold Standard)**

- Test
- result

**HIV ****infected**

**Sensitivity = A ****÷ ****(A+C) = 370 ****÷**** 374 = 98.9%**
**Specificity = D ****÷ (B+D) = ****624 ****÷ ****626 = 99.7%**
**           ****PPV = A ****÷ (A+B) = ****370 ****÷**** 372 = 99.5%**
**           ****NPV = D ÷ (C+D) = 624 ****÷ ****628 = 99.4%**

**Notes:**
This illustrates how to calculate Se, Sp, PPV, NPV
Evaluation of a rapid test on a panel of specimens that have been tested by the gold standard ??? is shown to contain HIV antibodies to 374 samples and no HIV antibodies to 626 samples.  Of the 374 serum samples that were antibody positive, the rapid test classified 370 of the samples as positive.  Of the 626 samples that were HIV antibody negative by the gold standard, 624 were classified by the rapid tests as not containing HIV antibodies.

While these results indicated very good performance, you must also keep in mind that the performance is influenced by the makeup of the population.

## HIV Rapid Test Performance

- No test is 100 % sensitive
- No test is 100 % specific
- Note:  Performance of tests and subsequent algorithm must be determined in context of population

**Notes:**
Performance of test and subsequent algorithm must be determined in context of population

## 				(Prevalence) (Se)
PPV=  
		(Prevalence) (Se) + (1- Prevalence) (1- Sp)

				(1-Prevalence) (Sp)
NPV=  	
		 (1-Prevalence) (Sp + (Prevalence) (1- Se)

**PPV=  **
**	****	****(Prevalence) (Se) + (1- Prevalence) (1- Sp)**
**	****	****	****	****(1-Prevalence) (Sp)**
**NPV=  ****	**
**	****	**** ****(1-Prevalence) (Sp + (Prevalence) (1- Se)**

**How Prevalence Affects PPV & NPV**

**Notes:**
If we know the sensitivity and specificity of the kit and the prevalence of HIV in the population, we can theoretically calculate the predictive value of the performed test. 

## How Prevalence Affects PPV & NPV (Cont’d)

**(10/100) (98.9/100)**
**=     -----------------------------------------------------------------------**  = **97.3%**
- (**10/100) (98.9/100) + (1- 10/100) (1- 99.7/100)**

**PPV for ****1%**** prevalence population:**
**(1/100) (98.9/100)**
**=  ---------------------------------------------------------------------------  = 76.9%**
**(1/100) (98.9/100) + (1- 1/100) (1- 99.7/100)**

**How Prevalence Affects PPV & NPV ****(Cont’d)**

## Testing Algorithm Describes the Sequence of Tests to be Performed 

- An HIV Positive Status should be based upon the outcome of 2 or more tests
- When two test results disagree (one is reactive, the other non-reactive), the finding is called “*discordant*.” In this case, a third test must be performed.

**Always follow the **
**sequence of the tests **
**in the algorithm**

**Notes:**
The order of the tests in the algorithm is important.

## Ideal Algorithm

- Tests need to be :
- Highly sensitive
- Highly specific
- Tests should not share the same false negatives and false positives
- 3rd test (if needed)

## 	Testing Algorithm*

** Develop appropriate algorithm diagram (parallel or serial) and insert names of HIV tests that represent test 1, 2 or 3*

**Notes:**
**Example of testing algorithm that countries may adopt based on in-country evaluation

## Exercise: Interpreting HIV Status Using Testing Algorithm

*Refer to Participant Manual*
*Work alone to determine HIV status *
*3 Minutes*

## 	Possible HIV Test Outcomes:  	Parallel Algorithm

| TEST 1 | TEST 2 | TEST 3 | HIV Status |
| --- | --- | --- | --- |
| Non-reactive | Non-reactive |  | Negative |
| Reactive | Reactive |  | Positive |
| Non-reactive | Reactive | Non-reactive | Negative |
| Reactive | Non-reactive | Non-reactive | Negative |
| Non-reactive | Reactive | Reactive | Positive |
| Reactive | Non-reactive | Reactive | Positive |

**Notes:**
Invalid test needs to be repeated 
Does not count toward outcome of test

## Summary

- Explain the importance of a tests’ Se, Sp, PPV, NPV
- Explain the testing algorithm adopted by MoH.  What rapid tests are used and in what order?