Results of a recent study show that the 10-year survival rates for children born with HIV who receive highly active antiretroviral therapy are more than double those for children who do not. As a result, survival rates have improved dramatically over the past two decades.

Most (84 percent) of the children in the study who did not survive were born before 1994, at least three years before highly active antiretroviral therapy (HAART) became widely available.

“As antiretroviral utilization milestones were achieved throughout the course of this study, in going from single-agent to dual-agent and then to triple-agent therapy (Highly Active Antiretroviral Therapy – HAART), there have been dramatic parallel improvements in mortality rates among the cohort resulting in prolonged overall survival,” said Dr. Bill Kapogiannis, program director of the Adolescent Medicine Trials Network for HIV/AIDS Interventions and lead author of the study.

However, the study authors noted that despite the large reductions in death rates, the average annual death rate of HIV-positive children during the HAART era remained 50-fold higher than the death rate of HIV-negative children of the same age during the same period in the United States.

They hypothesized that this may be due to increased susceptibility to death from other causes besides HIV, such as non-AIDS-defining infections.

“During this period, as deaths associated with opportunistic infections declined, the numbers of deaths not associated with these infections remain and thus, become more prominent,” said Dr. Kapogiannis.

HAART is defined as therapy involving at least three antiretroviral drugs, usually two nucleoside reverse transcriptase inhibitors combined with either a protease inhibitor, a non-nucleoside reverse transcriptase inhibitor, or an integrase inhibitor.

Since the introduction of HAART during the mid- to late-1990s, the frequency of deaths in adults and children with HIV has decreased considerably.

According to the study authors, while trends in survival and death among HIV-positive children have been examined in previous clinical trials, these trials have enrolled patients anytime from birth throughout childhood. As a result, deaths early on when children are particularly susceptible to infections might have been overlooked.

In this study, investigators compared death rates from birth in HIV-positive children born between 1986 and 2004. In particular, the researchers examined three time periods: the no antiretroviral therapy/monotherapy period from 1986 through 1990, the monotherapy/dual therapy period from 1991 through 1996, and the HAART period from 1997 through 2004.

The multicenter, retrospective study included HIV-positive pregnant women and their newborns in four cities in the U.S.: New York, Atlanta, Baltimore, and Newark, NJ. A total of 364 HIV-positive children were included in the study.

Results showed that the death rates of children in the first period and the second period were six and two times higher, respectively, than the death rate of children in the HAART era. However, the death rate in the HAART era remained 50 times higher than that of HIV-negative children of the same age.

The six-year survival rates for children born in the three eras were 57 percent, 76 percent, and 91 percent, respectively.

In addition, the 10-year survival rate for children who received HAART at any age was 94 percent, compared to 45 percent for children who did not receive HAART.

Eighty-one percent of deaths in the study occurred in children aged 3 years or less, and 61 percent of deaths occurred in children aged 2 years or less.

Results also showed that the percentage of deaths due to opportunistic infections declined over time, from 32 percent in 1986 to 1990, to 17 percent in 1991 to 1996, to 9 percent in 1997 to 2004.

The three most common causes of death in the study were end-stage AIDS (24 percent), opportunistic infections (19 percent), and pneumonia (15 percent).

Children who died were more likely to be born in the late 1980s or early 1990s, have a birth weight of less than 5.5 pounds (2.5 kg), be born prematurely (less than 37 weeks), or have low weight or height for their age at three months old. Children with thymic dysfunction, children who were infected with HIV before birth, and children who had not received zidovudine (Retrovir) during and before birth to prevent HIV infection were also at greater risk of death.

HIV transmission from mother-to-child before birth was associated with greater risk of death compared with HIV transmission during labor and delivery; however, the effect was only significant until two years of age.

For more information, please see the study in the Journal of Clinical Infectious Diseases.