Our ability to drastically reduce mother-to-child HIV transmission rates is good news indeed. But try explaining such good fortune to the estimated 10,000-plus children in the United States who are already infected with the virus. Yet, as we have been seeing with adults infected with the virus, controlling HIV in our youngest patients has gotten dramatically better over the last few years. Ten years ago, a pediatric HIV diagnosis was associated with a dismal prognosis: most infected children would die before their fifth birthday. Today, thanks to early access to care and triple-drug therapy, approximately half of all HIV-infected children will live to enter -- and graduate -- from high school and beyond. And with more information quickly emerging with respect to how HIV-infected children should be treated, we can expect the success rate to improve significantly.
Pediatric HIV Disease
Contrary to popular opinion, children are not simply mini-adults. HIV, even during the earliest stages of infection, can severely affect a child's development, whether it be physical growth, psychological evolvement, or emotional well-being. A child's immune system is also different from that of an adult's; HIV rapidly impairs its ability to control common childhood infections, such as bacterial-associated lung and ear infections and viral infections such as chicken pox. HIV also prevents the immune system from producing memory cells which, in adults, help ward off life-threatening infections like pneumocystis carinii (pneumonia), mycobacterium avium complex (MAC), and cytomegalovirus (CMV). Adding insult to injury is the fact that many HIV-infected children are born to mothers who abused alcohol and/or drugs while pregnant, which can exacerbate the problems associated with HIV considerably.
Researchers have shown that HIV-infected babies tend to have higher viral loads than adults, which can sometimes reach millions of HIV-RNA copies in a single milliliter of blood. As a result, the lessons we have learned treating adults with HIV hold true for children infected with the virus: a powerful combination of drugs should be used to lower children's viral loads to the lowest possible level.
Treating Pediatric HIV Infection
The United States Public Health Service -- the federal agency that oversees all that is health- and medical-related in this country -- has issued guidelines regarding how best to treat HIV-infected children. This, as Martha Stewart would say, is a good thing, as federal guidelines are the greatest tool we have in making sure that all HIV-infected children are sufficiently cared for and treated.
The Guidelines -- which are updated regularly and published by the Centers for Disease Control (CDC) -- are based on data collected from clinical trials. We know that anti-HIV drugs, particularly when used in combination with each other, work well in children. In a study looking at nevirapine (Viramune) in combination with AZT (Retrovir) and ddI (Videx) in eight infants aged two months to 16 months, the drugs succeeded in reducing viral load by 97% after four weeks of therapy. And, after 14 months, 2/8 (25%) infants studied.
Anti-HIV drugs are absorbed, metabolized, and eliminated from the body differently in children than in adults. In turn, various research teams have spent the better part of the last four years figuring out the correct dosages for each anti-HIV drug for children infected with the virus. At the present time, eight of the 15 drugs approved for adults are also approved for children. See Table on page 6 for more about drugs available in kid-friendly liquid/powder formulations and the doses of each compound used to treat pediatric HIV infection.
Preventing Opportunistic Infections
As with adults, HIV-infected children need to take preventive therapies (prophylaxis) to ward of common childhood- and AIDS-related infections. All children less than one year of age must take Bactrim or Septra (TMP/SMX) -- or if they cannot handle those drugs, either dapsone or aerosolized pentamidine -- to prevent pneumocystis carinii pneumonia (PCP). Children between the ages of one and two should take PCP prophylaxis if their CD4+ cells fall below 750. Two- to five-year olds with CD4+ cell counts below 500 should also be taking prophylaxis, as should all children six years or older with CD4+ counts below 200 cells/mm3
(similar to adult recommendations).
A rather unique HIV-related problem among children is lymphoid interstitial pneumonitis (LIP). Simply put, LIP is caused by a hyperactive immune response to a usually harmless infection in the lungs. The symptoms are similar to those of asthma (e.g., coughing, wheezing, shortness of breath, tightness in the chest) and, likewise, is treated with corticosteroids like prednisone, and with breath-restoring inhalers.
|Class||Drug||Liquid?||Pediatric Dose Range||Side Effects/Toxicities|
|yes(1)||90-180 mg/m2 q6-12h||Toxicities are similar but some are more common with specific drugs. All can cause headache, nausea and diarrhea. All cause bone marrow suppression but most common with ZDV. Peripheral neuropathy most common with d4T and pancreatitis most common with ddI. GI ulcers most common with ddC.|
|yes(1)||90-150 mg/m2 q12h|
|yes(1)||4 mg/kg q12h|
|yes(2)||1 mg/kg q12h|
|no||0.005-0.01 mg/kg q8h|
|no||8 mg/kg bid|
|yes(2, 3)||120 mg/m2 q12h||All three can cause headache and fatigue. Most striking toxicity is rash which can be severe and is frequently associated with systemic findings. Efavirenz can also cause central nervous system problems like confusion, muddled thinking, irritability, and vivid dreams.|
|no||400 mg tid (adult)|
|no||15 mg/kg qd|
|no||600mg tid (adult)||All can cause marked nausea and vomiting, asthenia, parasthesias. Indinavir notable for nephrolithiasis, nelfinavir for diarrhea. All cause significant drug interactions.|
|no||350-500 mg/m2 tid|
|yes(2)||300-400 mg/m2 tid|
|yes(4)||400-500 mg/m2 tid|
|no||1200 mg bid (adult)|
- Liquid formulation for neonates (newborns up to three months) approved.
- Liquid formulation for neonates (newborns up to three months) under study.
- Available from manufacturer noncommercially through an expanded access protocol.
- Available in powder that can be put into a liquid.
Source: Updated Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection (April 15, 1999)
Onwards and Upwards
While data certainly suggest that triple-drug anti-HIV therapy has made a tremendous impact on the lives of children living with the virus, it's not yet entirely understood to what extent these powerful drugs affect their young immune systems. In turn, maintaining children on prophylaxis remains the standard of care and it is still not clear whether or not immune system-related complications such as LIP are less likely to occur during successful anti-HIV therapy. Only time will tell. Luckily, HIV-positive children have a lot more of it to go around.
Tim Horn is the executive editor of The PRN Notebook, published by Physicians' Research Network in New York, and a member of CRIA's Research Advisory Committee.