Early Treatment for HIV-Infected Infants
With increased screening of pregnant women, many fetuses are known to be at risk for HIV infection. Therefore, infants born to HIV-infected women can be checked within the first weeks of life by PCR or culture assays for the presence of infectious virus in blood specimens. HIV infection can be definitively diagnosed in virtually all infants who have contracted the virus by six months of age. Nearly all such infants can be detected by one month. One positive test indicates presumptive infection and should be confirmed by a repeat test as soon as possible. Antibody testing is not a useful assay in children under 18 months of age since infants have maternal antibodies until then, and it is not possible to differentiate whether HIV antibodies belong to the child or are maternal in origin. If antibodies persist beyond this age range, only then do they indicate that the child is infected with HIV.
Yvonne Bryson, M.D., of the University of California, Los Angeles spoke at the Pediatric HIV Symposium in May 1997. She stated that 30% to 50% of the positive newborns can be diagnosed positive by culture at birth. The other 50% to 70% are negative at birth and positive at a later date. This suggests that babies who are negative by culture at birth but eventually test positive are being infected at the time of delivery. Treatments given to newborns who initially test negative may still be worthwhile as post-exposure prophylaxis or early therapy.
For infected infants, clinicians describe three distinct clinical outcomes. The first group is composed of rapid progressors who present symptoms early and become ill quickly. The second and largest group are the intermediate progressors who develop symptoms gradually. The third group are the long-term pediatric survivors, who include children up to eight years old without any symptoms or immune suppression. These children often have the less pathogenic non-syncytia-inducing (NSI) strain of HIV, low viral load, and comparatively high antibody levels.
According to recently published Women and Infant Transmission Study (WITS) data on 619 children, infants whose first positive culture was at 48 hours after birth or earlier showed higher viral load in their first two months than those infants who did not test positive until seven days or older. Peak viral levels at one month indicate that the majority of infected infants in the study were exposed around time of delivery. A small number of infected infants had high blood levels of HIV at birth, suggesting that they were infected in utero.
Babies in general have greater viral loads than adults. Viral load can frequently be very high in the first year of life, sometimes reaching levels in the millions. This is similar to primary infection in adults. But without treatment, a baby's viral load comes down more slowly and levels off at higher levels than an adult's viral load. According to the WITS study, viral load peaks at one to two months of age and then declines slowly to level off at 24 months. Median viral load for the infants in the study was 318,000 at one month and 256,000 at two months. Viral load then declined to a median of 34,000 at two years. This pattern may reflect the lower efficiency of an immature immune system in containing viral replication.
The WITS study demonstrated that viral load measurements could be used to predict severity of disease. Rapid progressors had high peak viral loads, median 724,000, from birth to two months. Infants with levels greater than 299,000 during the first few months had a 44% probability of progressing to AIDS or death within the first 24 months. Viral loads below 299,000 resulted in a 15% rate of progression, and infants with viral loads of less than 70,000 did not progress rapidly to AIDS and death within their first 18 months (Shearer W. New England Journal of Medicine. May 1997; 336(19):1337-42).
According to Dr. Bryson, infants who are treated earlier do better and their prognosis can be improved. If viral load can be reduced in the short term during the first few months of life, it may have a long-term effect. The prognosis for pediatric HIV has improved overall with early diagnosis and early treatment. The current thinking is to treat newly diagnosed babies very aggressively regardless of clinical status or viral load. Initiating combination antiviral therapy in infants in the period of primary infection potentially could provide durable suppression of viral replication and prevent selection of resistant mutations.
Dr. Bryson presented data from a trial using AZT, ddI and nevirapine in eight infants 2 to 16 months of age. The combination was well tolerated. By week four, there was at least a 1.5 log (97%) reduction in viral load in seven of the eight participants. Over the six-month trial period, viral load remained below baseline for these seven infants. In twins who were treated at 2.5 months for 14 months thus far, viral loads went to undetectable and viral culture tests were negative although HIV DNA PCR, a measure of surviving HIV-infected cells, remained positive (Luzuriaga K. New England Journal of Medicine. May 1997; 336(19):1343-9). Dr. Bryson was optimistic that these data indicated that viral eradication in infected children is possible.