HIV testing in children

James Nuttall Paediatric Infectious Diseases Unit,

Red Cross War Memorial Children’s Hospital & University of Cape Town

Paediatric HIV Course, 13 August 2016

Outline

• Based on Western Cape Consolidated Guidelines for HIV Treatment: Prevention of Mother-to-Child Transmission of HIV (PMTCT), Children, Adolescents and Adults, Amended Version 2015

• Identifying HIV-exposed newborns

• HIV testing of HIV-exposed newborns, infants & young children – Within the PMTCT programme

• Identifying HIV-exposed infants & children

– “Outside” the PMTCT programme

• Performance of different HIV rapid tests in children

• Consent & legal issues related to HIV testing of children

• Difficulties in confirming or excluding HIV infection in infants & young children

• Linking HIV testing to HIV care & antiretroviral treatment

A specific objective of the Western Cape ART programme

• To test all HIV exposed children under five years and treat all those found to be infected with HIV

• “Test & treat”

Identifying HIV-exposed newborns

• All newly diagnosed pregnant or breastfeeding clients with an unknown or previously negative HIV status must receive HIV Counselling and Testing (HCT) on the same day that they present to the healthcare facility.

• Pregnant women who test HIV negative at the initial test must be offered repeat HIV testing at the following intervals: – Around 20 weeks gestation (second trimester) – Around 32 weeks gestation (third trimester) – In labour/immediately after delivery – At 6 weeks after delivery (EPI visit) – Every 3 months while breastfeeding (ideally linked to contraceptive or baby

wellness visits)

• Clients should understand that retesting is done to detect seroconversion

or new infection during pregnancy or breastfeeding, which carries a high risk of HIV transmission to the infant.

HIV testing of HIV-exposed newborns, infants & young children Within the PMTCT programme

Never use a cord blood sample for infant HIV PCR testing at birth (contamination with maternal blood)

Identifying & HIV testing of HIV-exposed infants & children

“Outside” the PMTCT programme

Principles of diagnosis & exclusion of HIV infection

• Diagnosis of HIV infection: – In children <18 months of age, requires 2 positive HIV PCR test results each on

a separate specimen • Current US guidelines recommend HIV PCR testing to definitively confirm or exclude HIV

infection in perinatally HIV-exposed children <24 months of age

– In children ≥18 months of age, requires 2 positive HIV antibody test (HIV rapid tests or ELISA tests) results each on a separate specimen

• Can only exclude HIV infection in an HIV-exposed child at least 4 wks after

stopping ARV prophylaxis AND at least 6 wks after stopping breastfeeding – Negative HIV rapid test (Determine test)

• Current US guidelines recommend definitive exclusion of HIV infection based on 2 negative HIV antibody tests from separate specimens obtained at age ≥6 months provided the child has no other clinical or laboratory evidence of HIV infection and is not breastfeeding

– Negative HIV PCR test

Delayed seroreversion (after 18 months of age) in HIV-exposed uninfected infants/children

• 744 infants born to HIV-infected mothers since the introduction of cART for prevention of vertical transmission,

• 14% of infants remained seropositive after 18 months, 4.3% after 21 months, and 1.2% after 24 months.

• Maternal exposure to protease inhibitors was significantly associated with a later age of seroreversion.

Gutierrez M, Ludwig D, Khan S, et al. Has highly active antiretroviral therapy increased the time to seroreversion in HIV exposed but uninfected children? Clin Infect Dis 2012;55:1255–61

Age of the child determines the choice of test for HIV screening & confirmation

• <9 months: HIV PCR test – If positive, confirm with a 2nd HIV PCR test (no longer HIV viral load)

• 9-<18 months: Rapid HIV antibody screening test

– If positive, do an HIV PCR test • If positive, confirm with a 2nd HIV PCR test • If negative and breastfeeding within the last 6 weeks (or on ARV prophylaxis),

will need repeat HIV PCR test at least 6 weeks after stopping ARV prophylaxis and stopping breastfeeding

• ≥18 months: Rapid HIV antibody screening test

– If positive, confirm with rapid HIV antibody confirmatory test • If results are indeterminate, do HIV ELISA

Performance of different HIV rapid tests in children

• Different commercially available HIV rapid tests (RTs) differ in their sensitivity for detection of HIV antibodies in infants & young children at different ages when compared to the laboratory HIV ELISA test – WHO recommends that HIV RTs should have sensitivity ≥99% and specificity

≥98% under quality-assured, standardised and validated laboratory conditions

• Studies comparing different RTs have shown that in children <18 months

of age, the Determine RT has the best overall performance for detection and exclusion of HIV exposed infants without missing any HIV-infected children. – The Determine RT is recommended in the W Cape guidelines for use in

screening children <18 months for HIV exposure (?) – If the HIV RT result is negative but there is a strong clinical suspicion of HIV

infection in a child <18 months of age, an HIV PCR test should be done

• Among children ≥18 months of age, HIV RTs generally perform similarly to

among adults.

Sensitivity and specificity of various HIV RTs in comparison to standard laboratory HIV ELISA for detection of vertical HIV exposure in children

≤18 months of age

Sensitivity & positive likelihood ratio (LR+) of various HIV rapid tests (HIV RTs) for detection of HIV exposure (HIV ELISA+) in

children <18 months and <3 months of age

Nuttall, unpublished

Specificity & negative likelihood ratio (LR-) of various HIV rapid tests (HIV RTs) for excluding HIV

exposure (HIV ELISA-) in children <18 months of age

Nuttall, unpublished

Performance of various HIV rapid tests (HIV RTs) in detecting HIV-infected (HIV PCR+) children <18 months of age (HIV PCR+,

HIV RT+)

Nuttall, unpublished

Consent & legal issues related to HIV testing of children

• A child may be tested for HIV infection if testing is in the best interests of the child & consent is given by the child or the child’s parent or caregiver

• The child’s best interests apply “if it is clear that HIV testing will provide access to the continuum of care & promote a child’s physical & emotional welfare” (NDOH HIV Counselling & Testing Policy Guidelines 2010)

A child’s capacity to consent to HIV testing Children’s Act

• If the child is over 12 years, the child can give consent without his/her parent’s knowledge

• If the child is under 12 years & sufficiently mature enough to understand the benefits, risks & social implications of the test, then the child can consent him- or herself

• If the child is under 12 years & is not mature enough, then the parent or caregiver must give consent on the child’s behalf

What is meant by “sufficiently mature”? (NDOH HIV Counselling & Testing Policy Guidelines 2010)

• Can demonstrate that they understand information on HIV testing & can act in accordance with that appreciation

• Factors to consider: – Age: older the child more likely to have sufficient maturity

– Knowledge of HIV & its implications are more likely to understand its consequences

– Views: ability to articulate their views on HIV testing & whether it is in their best interests

– Personal circumstances & motivation for HIV testing

Pre & post-test counselling on HIV infection

• Pre- & post-test counselling must be provided to the child

• The parent or caregiver must also be counselled if they have knowledge of the test or have consented on the child’s behalf

• Where children are counselled & tested, staff should have appropriate understanding or specific training in child development, communication with children, & appropriate counselling guidelines – In order to assess the developmental capacity of children to

understand the implications of the HIV test – Advise children with the maturity to undergo counselling on

their own that they may voluntarily involve their parents or caregivers in the counselling process

(NDOH HIV Counselling & Testing Policy Guidelines 2010)

Disclosure of HIV status

• Children’s right to choose whether or not to disclose their HIV status is rooted in their constitutional right to privacy & physical integrity – Health professionals may not unduly interfere in a

child’s right to choose whether or not to disclose

– The child’s right to freedom of choice is not absolute & can be limited if reasonable & justifiable (e.g. risk of harm to a 3rd party, such as unprotected sex with another child)

Jamieson & Lake, Children’s Act Guide for Health Professionals, 2013

Difficulties in confirming or excluding HIV infection in infants & young children: Case

• Antenatal: – Mother booked at MOU and initiated on ART – Defaulted ART and ANC after 1 month. – Presented to hospital in labour and delivered there.

• Post-partum:

– Baby started on NVP only as prophylaxis. – Birth HIV PCR test result came back as positive – Mother & infant not traced

• Presented at a clinic at 4 weeks of age:

– Infant still receiving NVP prophylaxis. – Bloods done: confirmatory HIV PCR result was negative and HIV viral load undetectable. – Mother admitted to poor adherence after restarting ART at birth (HIV VL was over 70 000) . – Breastfeeding. – Unstable home environment.

• Is this infant HIV-infected? How would you manage mother & child?

Principle

• Diagnosis of HIV infection: – In children <18 months of age, requires 2 positive HIV

PCR test results each on a separate specimen

• Can only exclude HIV infection in an HIV-exposed

child – at least 4 wks after stopping ARV prophylaxis or ART

AND – at least 6 wks after stopping breastfeeding – If <9 months of age, an HIV PCR test is generally

recommended

Managing indeterminate HIV PCR test results

• Laboratory diagnosis of HIV infection in infants <18 months of age requires 2 HIV PCR + results each on a separate specimen

• An HIV PCR result can be positive, negative or indeterminate

• An indeterminate HIV PCR result means that the test is inconclusive (not clearly positive or negative) & requires immediate further testing

• Repeat HIV PCR and HIV viral load testing needs to be performed urgently & the patient managed accordingly

Managing indeterminate HIV PCR test results

• Infants in which the diagnosis of HIV remains inconclusive or where discordant results have been obtained (i.e. a positive HIV PCR followed by a negative HIV PCR and undetectable HIV viral load) require urgent discussion with specialist clinician and pathologist.

• Repeat HIV testing and clinical monitoring is required until the HIV status is established

• Infants cannot be considered HIV-uninfected unless repeat testing occurs at least 4 weeks after infant prophylaxis (or cART) has been discontinued and 6 weeks after cessation of breastfeeding

• Counselling the mother/primary caregiver regarding the indeterminate result is of paramount importance to ensure successful follow-up and arriving at a definitive diagnosis

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Unique identifier to de–duplicate repeat and confirmatory HIV PCR tests - enumerate no. HIV-infected infants - monitor guideline implementation e.g. confirmatory testing

Thanks to Gayle Sherman for slide