They also urge national governments to invest in better methods for
diagnosing HIV infection in children below 18 months, where diagnosis with HIV
antibody tests is complicated by the presence of maternal antibodies in the
WHO wants national governments to strengthen laboratory capacity so that they
can use real-time PCR testing to detect genetic material from the virus itself
(HIV RNA or DNA), rather than having to wait until a child is 18 months old.
But the guidelines point out that while HIV antibody testing can't be used to
diagnose HIV definitively before 18 months of age, it can be used to rule out
HIV infection as early as 9-12 months of age if they are not breastfed or ceased
breastfeeding more than six weeks before the antibody test, as most uninfected
HIV-exposed infants have lost maternal antibody by the age of 12 months. A
positive test at this point in an asymptomatic child should be confirmed at 18
months of age.
Virological testing to detect HIV should also wait for at least six weeks after
breastfeeding ceases, the WHO expert panel concluded, except in children whose
mothers are receiving antiretroviral therapy. In these infants, virological
testing can be carried out while breastfeeding continues.
Where virological testing is not available clinical signs of HIV disease will
continue to be the main means of diagnosis in children under the age of 18
months, but the WHO guidelines warn that clinical algorithms are rarely more
than 70% sensitive and are least reliable in children below the age of 12
months, underscoring the need for diagnostic alternatives that can be used in
children below the age of 18 months where laboratory facilities are limited or
A presumptive diagnosis can be made in children below the age of 18 months if:
* the child is confirmed as HIV-positive
* and diagnosis of an AIDS indicator condition can be made or the
infant is symptomatic with two or more of the following: oral thrush, severe
pneumonia or severe sepsis.
All children below the age of 12 months with symptoms of advanced or severe HIV
disease should receive antiretroviral treatment because the risk of death is so
high children with advanced symptomatic HIV disease (WHO stage 3) above the age
of 12 months may not require treatment if their immunodeficiency is less
advanced. The recommended threshold for starting treatment is a CD4 percentage
below 20 in children aged 12-35 months, < 15% aged 36 to 59 months and <
15% in children of five years and above. Similar guidelines hold for all
children with WHO stages 1 and 2 disease, including infants below the age of 12
In children, first-line treatment should consist of AZT (zidovudine) and 3TC (lamivudine)
or d4T (stavudine) plus 3TC or abacavir plus 3TC together with either nevirapine
or efavirenz. In children below the age of three years nevirapine should be used
because appropriate weight-related dosing has not been determined for efavirenz.
A triple nucleoside regimen of AZT/3TC/abacavir may also be used, particularly
in children receiving treatment with rifampicin for TB.
The guidelines note that large volumes of AZT liquid formula are poorly
tolerated, and that although d4T is better tolerated, it carries a long-term
risk of lipoatrophy in children. Tenofovir, now recommended for first-line
treatment in adults, is not available in a paediatric formulation and dosing
studies of the tablet formulation have not been carried out in children.
Fixed dose triple combinations for children containing nevirapine are being
developed by several Indian companies and are expected to be approved within the
Detailed dosing tables for all drugs according to weight are available within
the guidelines document.
The guidelines say that for children exposed to antiretrovirals around the time
of birth as part of prevention of mother to child transmission, it is still too
early to say whether drug resistance acquired during short-term exposure will
compromise the paediatric response to antiretroviral therapy. Ongoing trials in
South Africa and Botswana may provide an answer, WHO says. Continuing exposure
to antiretrovirals in breast milk should not affect the choice of treatment for
a breastfeeding infant that requires treatment.
For children experiencing failure of first-line treatment, second-line treatment
should consist of ddI and abacavir unless abacavir was used in first-line
treatment, plus either lopinavir/ritonavir (Kaletra
) or nelfinavir (Viracept
Nutritional support recommended
WHO points out that children and infants who have symptomatic HIV disease or who
are recovering from an acute infection need to consume 20-30% more calories than
HIV-negative children if they are not suffer poor growth and poor recovery from
Since severe wasting is a common clinical presentation in children with HIV
infection, the guidelines advise that severe malnutrition needs to be stabilised
before antiretroviral therapy is begun. Although this phase shouldn't take
longer than ten days in HIV-negative children, the guidelines warn that the
response to malnutrition treatment may be limited and slow in HIV-positive
children. If after six to eight weeks a child has not achieved a weight for
height of 85% as a result of special feeding, antiretroviral therapy should
probably be initiated.
Once a child begins to gain weight on antiretroviral treatment, drug doses need
to be reviewed regularly to ensure that the child is still receiving an adequate
dose, WHO warns. Conversely, there are no available data on the effectiveness,
pharmacokinetics and safety of antiretrovirals in severely malnourished
children, so it is not known what doses are necessary in children who are
seriously underweight for their age (drug metabolism is governed by age as well
as body size).
The guidelines also contain detailed discussion of monitoring protocols for
children with HIV, as well as considerations for antiretroviral therapy in
adolescents and methods for judging treatment failure in children where
virological monitoring is not available.
The full guidelines document can be downloaded from the WHO website at http://www.who.int/hiv/pub/guidelines/art/en/index.html