Antiretroviral therapy of HIV infection in infants and children: towards universal access: recommendations for a public health approach 2010 revision

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Antiretroviral therapy of HIV infection in infants and children: towards universal access: recommendations for a public health approach 2010 revision

Recommendations

In sick infants in whom HIV infection is being considered as an underlying cause of symptoms and signs, and virological testing is not available, HIV serological testing and use of the clinical algorithm for presumptive clinical diagnosis of HIV infection is strongly recommended.

It is strongly recommended that HIV serological assays used for the purpose of clinical diagnostic testing have a minimum sensitivity of 99% and specificity of 98% under quality assured laboratory conditions

It is strongly recommended that HIV virological testing be used to diagnose HIV infection in infants and children below 18 months of age

In infants and children undergoing virological testing, the following assays (and respective specimen types) are strongly recommended for use: HIV DNA on whole blood specimen or DBS; HIV RNA on plasma or DBS; Us p24 Ag on plasma or DBS

It is strongly recommended that all HIV-exposed infants have HIV virological testing at 4–6 weeks of age or at the earliest opportunity thereafter

It is strongly recommended that all infants with unknown or uncertain HIV exposure being seen in health-care facilities at or around birth or at the first postnatal visit (usually 4–6 weeks) or other child health visit have their HIV exposure status ascertained

Initiate ART for all HIV-infected infants diagnosed in the first year of life, irrespective of CD4 count or WHO clinical stage.

Initiate ART for all HIV-infected children between 12 and 24 months of age irrespective of CD4 count or WHO clinical stage.

Initiate ART for all HIV-infected children more than 5 years of age with CD4 count ≤350 cells/mm3 (as in adults), irrespective of WHO clinical stage.

Initiate ART for all HIV-infected children with WHO HIV clinical stages 3 and 4, irrespective of CD4 count

Initiate ART for any child less than 18 months of age who has been given a presumptive clinical diagnosis of HIV infection.

For infants not exposed to ARVs, start ART with nevirapine (NVP) + 2 nucleoside reverse transcriptase inhibitors (NRTIs).

For infants exposed to maternal or infant nevirapine (NVP) or other non-nucleoside reverse transcriptase inhibitor (NNRTI) used for maternal treatment or PMTCT, start ART with lopinavir/ritonavir (LPV/r) + 2 nucleoside reverse transcriptase inhibitor (NRTI).

For infants whose exposure to ARVs is unknown, start ART with nevirapine (NVP) + 2 nucleoside reverse transcriptase inhibitor (NRTI).

For children between 12 and 24 months of age exposed to maternal or infant nevirapine (NVP) or other non-nucleoside reverse transcriptase inhibitor (NNRTI) used for maternal treatment or PMTCT, start ART with lopinavir/ritonavir (LPV/r) + 2 nucleoside reverse transcriptase inhibitor (NRTI)

For children between 12 and 24 months of age, not exposed to non-nucleoside reverse transcriptase inhibitor (NNRTI) , start ART with nevirapine (NVP) + 2 nucleoside reverse transcriptase inhibitor (NRTI)

For children more than 24 months and less than 3 years of age, start ART with nevirapine (NVP) + 2 nucleoside reverse transcriptase inhibitor (NRTI)

For children 3 years of age and above, start ART with an nevirapine (NVP) or efavirenz (EFV)-containing regimen + 2 nucleoside reverse transcriptase inhibitor (NRTI).

For infants and children, the nucleoside backbone for an ART regimen should be one of the following, in preferential order: • Lamivudine (3TC) + zidovudine (AZT) • 3TC + abacavir (ABC) • 3TC + stavudine (d4T)

For children >3 years of age with TB, the preferred regimen is efavirenz (EFV) + 2 nucleoside reverse transcriptase inhibitor (NRTI)

For infants and children less than 3 years of age with TB, the preferred regimens are nevirapine (NVP) + 2 nucleoside reverse transcriptase inhibitor (NRTI) or a triple nucleoside regimen.

For a child or adolescent with severe anaemia (<7.5 g/dl) or severe neutropenia (<500 cells/mm3), the preferred regimen is nevirapine (NVP) + 2 nucleoside reverse transcriptase inhibitor (NRTI) (avoid zidovudine (AZT)).

For adolescents >12 years of age with hepatitis B, the preferred regimen is tenofovir disoproxil fumarate (TDF) + emtricitabine (FTC) or lamivudine (3TC) + non-nucleoside reverse transcriptase inhibitor (NNRTI) .

CD4 should be measured at the time of diagnosis of HIV infection, and every 6 months thereafter. Monitor with increasing frequency as CD4 count approaches threshold for starting ART.

CD4 should be measured prior to initiating ART

CD4 should be measured every 6 months after initiating ART.

Measure CD4 if new clinical staging events develop, including growth faltering and neurodevelopmental delay.

Where capacity for CD4 measurement is limited, target the use of CD4 monitoring to assess the significance of clinical events.

Viral load determination is desirable, but not essential, prior to initiating ART.

Viral load should be assessed to confirm clinical or immunological failure where possible, prior to switching treatment regimen.

Baseline haemoglobin level (and white cell count, if available) should be assessed at initiation of ART

For infants and children, measure haemoglobin at week 8 after initiation of zidovudine (AZT)-containing regimens, or more frequently if symptoms indicate.

Growth, development and nutrition should be monitored monthly

(HIV CLINICAL AND LABORATORY MONITORING) Laboratory monitoring for toxicity should be symptom directed.

A switch to a second-line regimen is recommended when: • clinical failure is recognized, and/or • immunological failure is recognized, and/or • virological failure is recognized.

Clinical failure is defined as the appearance or reappearance of WHO clinical stage 3 or stage 4 events after at least 24 weeks on ART in a treatment-adherent child.

Virological failure is recognized as a persistent viral load (VL) above 5000 RNA copies/ml, after at least 24 weeks on ART, in a treatment-adherent child.

After failure on a first-line non-nucleoside reverse transcriptase inhibitor (NNRTI) -based regimen, a boosted PI plus 2 nucleoside reverse transcriptase inhibitor (NRTI) are recommended for second-line ART

lopinavir/r is the preferred boosted PI for a second-line ART regimen after failure on a first-line non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen.

After failure on a first-line regimen of zidovudine (AZT) or stavudine (d4T) + lamivudine (3TC), abacavir (ABC) + 3TC is the preferred nucleoside reverse transcriptase inhibitor (NRTI) backbone option for second-line ART; ABC + ddI is an alternative

After failure on a first-line regimen of abacavir (ABC) + lamivudine (3TC), zidovudine (AZT) + 3TC is the preferred nucleoside reverse transcriptase inhibitor (NRTI) backbone option for second-line ART; AZT + ddI is an alternative.

All HIV-infected infants and children exposed to TB through household contacts, but with no evidence of active disease, should begin isoniazid preventive therapy (IPT).

Infants living with HIV, who are unlikely to have active TB and are not known to be exposed, should not receive isoniazid preventive therapy (IPT) as part of a comprehensive package of HIV care.

Children living with HIV who are more than 12 months of age and who are unlikely to have active TB on symptom-based screening and have no contact with a TB case should receive 6 months of isoniazid preventive therapy (IPT) (10 mg/kg/day) as part of a comprehensive package of HIV prevention and care

Any child with active TB disease should begin TB treatment immediately, and start ART as soon as tolerated in the first 8 weeks of TB therapy, irrespective of the CD4 count and clinical stage

The preferred first-line ARV regimen for infants and children less than 3 years of age who are taking a rifampicin-containing regimen for TB is 2 nucleoside reverse transcriptase inhibitor (NRTI) + nevirapine (NVP) or a triple NRTI regimen.

The preferred first-line ARV regimen for children more than 3 years of age who are taking a rifampicin-containing regimen for TB is 2 nucleoside reverse transcriptase inhibitor (NRTI) + efavirenz (EFV).

The preferred first-line ARV regimen for infants and children less than 2 years of age who have been exposed to nevirapine (NVP) and are taking a rifampicin-containing regimen for TB is a triple nucleoside reverse transcriptase inhibitor (NRTI) regimen.

For all HIV-infected children, anti-TB therapy should be started immediately upon the diagnosis of TB; ART should continue.

HIV-infected children should be routinely assessed for nutritional status, including weight and height at scheduled visits, particularly after initiation of ART

HIV-infected children on or off ART who are symptomatic, have conditions requiring increased energy (e.g. TB, chronic lung disease, chronic OIs or malignancies), or have weight loss or evidence of poor growth should be provided with 25 – 30% additional energy

HIV-infected children who are severely malnourished should be managed as per the guidelines for uninfected children and provided with 50 – 100% additional energy.

HIV-infected children should receive one recommended daily allowance (RDA) of micronutrients daily. If this cannot be assured through the diet, or there is evidence of deficiency, then supplementation should be given.

HIV-infected infants and children between 6 and 59 months of age should receive high-dose vitamin A supplementation every 6 months, as per the guidelines for uninfected children

HIV-infected children who have diarrhoea should receive zinc supplementation as part of management, as per the guidelines for uninfected children.

For infants and young children known to be HIV infected, mothers are strongly encouraged to exclusively breastfeed for 6 months and continue breastfeeding as per recommendations for the general population (up to two years of age and beyond).