Treat all under-twos with HIV immediately, says WHO

All infants and children with HIV below two years of age should receive antiretroviral treatment regardless of their CD4 count or disease stage, and treatment should start earlier than previously recommended for all other children with HIV, the World Health Organization (WHO) recommends in new guidelines issued on June 10th.

The new guidelines emphasise the importance of early diagnosis of HIV infection, with fast-tracking of positive results to mother and child.

After diagnostic virological testing – preferably carried out within four to six weeks of birth in infants known to have been exposed to HIV – antiretroviral therapy should begin without delay, before a confirmatory virological test is carried out.

Where virological testing is not available and infants have symptoms suggestive of HIV disease, a combination of antibody testing and use of the WHO clinical algorithm for HIV diagnosis in children should be used to determine whether an infant is highly likely to have HIV.

Virological testing is recommmended because antibodty testing may not produce an accurate result in children before the age of 18 months, due to the persistence in the child's bloodstream of the mother's HIV antibodies. These disappear as the child's own immune system matures by the age of 18 months. If HIV antibodies are still present after this time, HIV infection in the child can be diagnosed with confidence.

Virological testing, which looks for HIV itself, allows for diagnosis soon after birth. Many countries are now using dried blood spots, from samples taken at the time of delivery or at the first clinic visit after delivery, as means of obtaining an early infant diagnosis from a well-equipped laboratory.

In children aged two to five, all those with CD4 counts below 750 or a CD4 percentage of 25 or less should receive immediate antiretroviral treatment, regardless of whether they are symptomatic or not.

In children over five years of age the same guidelines apply as for adults – immediate treatment for anyone with a CD4 count below 350.

Regardless of CD4 count, any child with WHO stage 3 or 4 HIV disease should receive antiretroviral treatment, WHO recommends.

WHO says that one-third of infants with HIV will die in the first year of life without treatment, and half will die before reaching two years of age. Only 38% of children eligible for treatment under previous WHO recommendations were getting it by the end of 2008, according to WHO estimates, and treatment coverage is likely to be considerably lower once the new recommendations are taken into account.

The new guidelines also recommend that nevirapine (Viramune) should only be used in infants and children below the age of two who weren’t exposed to the drug during pregnancy or breastfeeding. Any infant or child previously exposed to nevirapine should instead receive lopinavir/ritonavir (Kaletra), due to the risk of a sub-optimal response to nevirapine-based ART caused by the persistence of nevirapine-resistant virus.

In children aged three or over diagnosed with TB, efavirenz should be used; in under-threes, in whom efavirenz is not licensed for use, treatment in cases of TB/HIV co-infection should be carried out with nevirapine or a triple nucleoside regimen.

The recommended nucleoside analogue backbones are AZT/3TC, abacavir/3TC or d4T/3TC. AZT is not recommended in cases of anaemia or neutropenia, since it may make these problems worse.

In adolescents with hepatitis C, efavirenz should be used in preference to nevirapine due to the risk of liver toxicity; in adolescents with hepatitis B, tenofovir and FTC should be used as the nucleoside backbone because they are active against hepatitis B.

The new guidelines recommend that CD4 counts should be monitored every six months from HIV diagnosis, and prior to starting ART; once on ART, CD4 monitoring should take place every six months. If CD4 testing is difficult, it should be prioritised in cases where the significance of clinical events needs to be assessed, in both treated and untreated children.

Further details on treatment switching and monitoring are contained in the Executive summary of recommendations, now available online.

The guidelines also recommend routine assessment of nutritional status, both off and on ART, with food supplementation for symptomatic children who have lost weight, show signs of poor growth or who have tuberculosis or opportunistic infections. A daily micronutrient supplement is also recommended where the diet is inadequate or the child appears to be deficient.

Children with HIV who are exposed to TB but have no sign of active disease in the household should receive isoniazid preventive therapy (IPT), as should children over 12 months of age who have not been exposed to TB.

All children with HIV diagnosed with TB should start antiretroviral therapy immediately. Further details of recommended regimens and dosing are contained in the Executive summary.