DRC: Use of ARVs Reduces Mortality among HIV-Infected Children

By Staff Writer

KINSHASA---A new study published in PLosMedicine, an open access peer reviewed medical journal by the American Public Library of Sciences finds that the use of highly active antiretroviral therapy (HAART) among HIV-infected children reduces their mortality by nearly 75 per cent. Observational data from HAART-naïve children enrolled into an HIV care and treatment programme in Kinshasa, Democratic Republic of the Congo, between December 2004 and May 2010 were analyzed. The researchers used marginal structural models to estimate the effect of HAART on survival while accounting for time-dependent confounders affected by exposure.

In 2009, an estimated 2.5 million children were living with HIV, the majority of whom (2.3 million) were in sub-Saharan Africa. Most (90 per cent) of these children acquired HIV from their HIV-infected mothers during pregnancy, birth, or breastfeeding, highlighting the importance of giving effective drugs for the prevention of mother to child transmission. As such interventions are still not widely accessible or available in most resource-limited countries, where the burden of HIV is highest, every day an estimated 1,000 children were newly infected with HIV in 2009, but only 360,000 children were receiving highly active antiretroviral therapy (HAART).

Although HAART improves the survival of adults living with HIV, less is known about the degree to which HAART affects the survival of HIV-infected children—although response to antiretroviral treatment is known to differ across age groups. Furthermore, as the course of HIV disease in children is different from that in adults (partly because of the impact of the virus on the immature thymus, which can lead to high HIV RNA viremia and rapid death), it is inappropriate to extrapolate results from studies of adults to paediatric populations. Therefore, it is imperative that the effect of HAART on survival be quantified specifically in children.

This study was conducted bearing in mind that although some investigations have taken place in paediatric cohorts from such countries (for example, Côte d'Ivoire, Haiti, Lesotho, Thailand, and Zambia), the effect of HAART on mortality has not been accurately quantified among children in a resource-deprived setting. Therefore, in this observational clinical cohort study, the researchers investigated the effect of HAART on mortality in HIV-infected children in Kinshasa, in the Democratic Republic of the Congo (DRC).

The researchers analyzed data from 790 children enrolled into an HIV programme in Kinshasa, DRC, between December 2004 and May 2010 and used a statistical model (marginal structural models) to adjust for time-dependent confounding factors, such as the fact that HAART is typically initiated in sicker patients, for example, those with lower CD4 cell percentages. Assuming that all children starting HAART received it uninterruptedly throughout follow-up, using this statistical model, the researchers were able to compare the hazard ratio of death had all children initiated HAART to that had no children initiated HAART during follow-up.

In the study, 619 out of the 790 children (78.4 per cent) initiated HAART during follow-up and were followed for a median of 31.2 months, with a median of 30 HIV care visits. Of those who started treatment, 110 (17.8 per cent) switched to an alternative regimen because of an adverse event or treatment failure. During the 2,089.8 accrued person-years of follow-up, 80 children (10.1 per cent) died, giving an overall mortality rate of 3.8 deaths per 100 person-years. The unadjusted mortality rate ratio comparing HAART to no HAART was 0.54. Using a marginal structural model, the researchers estimated that compared to no HAART, HAART reduced the hazard (rate) of mortality during follow-up by 75 per cent.

These findings show that treatment with HAART markedly improved the survival of children infected with HIV in Kinshasa, DRC, and suggest that HAART is as effective in improving the survival of HIV-infected children in a severely resource-deprived country (still recovering from civil war) as in more resource-privileged settings—an important finding given that the vast majority of children receiving HAART live in resource-poor areas. This study provides additional evidence that accelerating rollout of antiretroviral therapy to children with HIV in resource-poor countries is lifesaving and effective. Future research needs to address how effective HAART is in understudied populations in resource-poor countries, such as undernourished children or those with co-infections such as tuberculosis.