HIV Infection in Children: Clinical Review

HIV has transformed pediatric practice in developing countries. A specialty that once dealt mainly with acute illnesses is now consumed, in many settings, with managing chronically ill and dying children. Last year, 600,000 children were newly infected with HIV, with 90 percent of occurrences in sub-Saharan Africa. Almost all acquired the virus by vertical transmission, from mother to child. According to the authors, "The statistics do not adequately portray the suffering and disrupted lives of the most vulnerable of the world's population."

UNAIDS recently reported that by 2010, a doubling of child mortality is expected. Globally, the number of orphans from AIDS will increase from 13.2 million to 44 million by 2010. "Finding appropriate responses to this crisis must rank as the single most important global challenge to child health in the next decade," the authors wrote.

The authors' article is based upon a Medline search of papers and reviews, unpublished material, presentation, abstracts and personal communications with scientists and clinicians.

HIV disease progresses more rapidly in children. Children have higher HIV viral loads than adults, and they have recurrent invasive bacterial infections more often. Opportunistic infections often present as primary diseases with a more aggressive course. The cellular responses to HIV in children are similar to adults, and children respond almost as well as adults to antiretroviral regimens.

Reducing vertical transmission from mother to child is paramount, particularly in resource poor countries, where up to 40 percent of pregnant women are infected with HIV and 25-48 percent of their children inherit the disease. In populations where breast-feeding is uncommon, most transmission occurs in the intrapartum period. In communities where breast-feeding is common, postpartum transmission contributes from a third to a half of all infections.

Antiretroviral treatment reduces vertical transmission by decreasing maternal viral load and by offering prophylaxis to infants before and after exposure. Longer antenatal treatment (28 weeks forward) with zidovudine is better than a shorter course, and this regimen combined with three days of zidovudine for the infant may be as effective as a six-week course postnatal.

Currently, 95 percent of vertical transmission occurs in developing countries. Nevirapine, a non-nucleoside reverse transcriptase inhibitor, is the most effective and practical treatment regimen. Administration to the mother at time of delivery and a dose given to the infant within 72 hours of birth shows a 47 percent reduction in transmission. The drug costs only about $4 for the course and the manufacturer has agreed to provide it at no cost to developing countries. Despite this and recommendations from WHO and UNAIDS that the prevention of vertical transmission of HIV be included in a minimum standard of care, most governments have been slow in responding. Many have difficulties providing the prerequisite antenatal HIV screening, counseling and distribution, and many fear toxicity and resistance.

According to the authors, there is no evidence that exposure to zidovudine has serious side effects. There are concerns about the toxicity of antiretroviral treatment in pregnancy but current data indicate that the benefits of treatment far outweigh any potential harm.

Elective cesarean delivery reduces HIV transmission by more than half over other modes of delivery, with administration of zidovudine offering additional benefit (85 percent reduction). In resource poor countries cesarean delivery is not appropriate due to cost constraints and the risk of postoperative complications. Simpler and cheaper interventions like vagina cleansing with chlorhexidine during labor and supplements like Vitamin A are ineffective.

The controversy over breast-feeding versus formula feeding in resource-poor countries continues. Research on three key issues may change policy. One critical issue is the effect of breast-feeding on mother and child. A Kenyan study showed that breast-fed children are more likely acquire HIV than non-breast-fed (36.7 percent versus 20.5 percent). Mortality in the breast-fed group is greater. For mothers the effect of breast-feeding was a 3.2 times higher mortality. Patterns of breast-feeding are also at issue. Exclusive breast-feeding for the first three months may be as safe as formula feeding and much safer than mixed formula and breast-feeding. But this finding needs to be confirmed. Thirdly, the evidence of the advisability of antiretroviral treatment in communities where breast-feeding is the norm are conflicting. One study showed no reduction in overall HIV transmission at 18 months. Two other studies showed 42 percent and 28 percent reduction at ages 12 and 24 months respectively, despite continued breast-feeding.

Vaccine research has progressed but, according to the authors, the "challenges in developing safe and effective vaccines are daunting. . . ."Intriguing examples of multiply exposed adults who remain seronegative long-term suggest that partial natural protection can occur. Routine childhood vaccinations play an important role in preventing common illnesses that affect HIV-infected children. HIV-infected children show few adverse reactions to routine vaccinations.

To date, the FDA has approved 11 different antiretroviral treatments for children. Antiretroviral drugs have dramatically reduced morbidity and mortality in both adults and children. From long-standing viral suppression to ever more promising new drugs with novel targets, future treatments will almost certainly emerge and be especially effective at immune modulation. But antiretroviral treatment has several limitations, not the least of which is that it fails to rid the body of infected cells (resting memory CD4 cells) and fails to completely suppress viral replication. Treatment failures often occur and viral resistance to drugs is increasing. Most importantly, according to the authors, "It remains unaffordable for 95 percent of infected adults and children worldwide. Even if the cost issue was resolved, the complexity of the various regimens and the many side effects make adherence difficult and the infrastructure needed to support antiretroviral treatment limits its widespread availability."

Rather than rejecting these treatments, the authors recommend alternative and innovative treatment options like optimal timing of treatment, with prescriptions for children based upon easily observed clinical signs and symptoms, as is currently practiced with Haitian adults.

"The key to preventing HIV infection in children clearly lies in preventing their parents from acquiring the disease. Unfortunately, except for isolated successes such as in Uganda and Thailand (associated with enlightened sex education and condom use), there is little hope that the expansion of the pandemic will be halted soon," the authors said. More effort needs to be directed at socio-cultural and economic aspects of prevention and in linking individuals to biomedical approaches, they concluded.

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