A study notes the need to start HIV treatment on perinatally infected babies within the first 12 weeks of life

• The results highlight the need for early diagnosis and treatment in newborns, since a small viral reservoir might help future medical interventions to cure HIV infection. However, the therapy must be maintained continuously, since the size of the reservoir increases when the treatment is interrupted.
• Although there are hardly any cases of HIV mother-to-child transmission in Spain, there were 220,000 new HIV infections in children in the world in 2014, representing more than 600 infections per day. In 2013, only 42% of HIV-exposed infants received early infant diagnostic services in their first two months of life.
• The study is a collaboration of the IrsiCaixa AIDS Research Institute and the Hospital Gregorio Marañón, besides the contribution of Spanish multiple pediatric services.

A study based on Spanish children with vertically transmitted HIV infection has shown that initiation of antiretroviral therapy (ART) during the first 12 weeks of life reduces 6 times the size of viral reservoirs, whenever treatment is maintained without interruption. Viral reservoirs are viruses that remain dormant inside cells and react when the therapy is stopped, so reducing their size might benefit future therapeutic strategies to cure HIV infection. The study, published in the American journal Clinical Infectious Diseases, has been coordinated by researchers from the IrsiCaixa AIDS Research Institute, promoted by the Obra Social “la Caixa” and the Health Department of the Generalitat de Catalunya, and the hospital Gregorio Marañón in Madrid. Multiple pediatric services in the Paediatric Spanish AIDS Research Network Cohort (coRISpe) have also collaborated.

Given the potential toxicity of the treatment, initially TAR administration to children was only recommended when symptoms of infection started or CD4 T cell count (the HIV target cells) dropped below a level that could be considered potentially hazardous to the health. However, in recent years, several studies have suggested the benefit of starting early treatment in all HIV-infected infants, so international guidelines now recommend starting therapy during the first year of life, regardless of whether the child has clinical symptoms or his CD4 T cell count. The study published in Clinical Infectious Diseases was designed to check whether initiating ART during the first 12 weeks would be more beneficial than waiting beyond week 12.

The retrospective study included 23 perinatally HIV-infected children born in Spanish hospitals between 2004 and 2009. They were divided into two groups: 14 who had started therapy during the first 12 weeks of life, and 9 who had started between week 12 and 54. The results indicate that viral reservoirs in the first group were 6 times smaller than those of the second group. Although it is still being investigated, scientists agree that size limitation in viral reservoirs may play a key role in avoiding virus replication after treatment interruption, which could be defined as "functional cure". Today, thanks to current therapies that increase the life expectancy of HIV-infected people, "children are the best candidates to benefit, in the future, from therapeutic strategies to cure”, says Javier Martinez-Picado, ICREA researcher and head of the group of Retrovirology and Clinical Studies of IrsiCaixa.

New infections in children

The results highlight the importance of carrying out seropositivity tests as quickly as possible and administering immediate therapy when HIV infection is diagnosed in a newborn. In Spain, thanks to the obligation to carry out HIV testing to all pregnant women and administrate ART to prevent transmission during pregnancy and childbirth, there are hardly any cases of infected babies (according to the National Registry of AIDS cases, in 2013 there were in Spain 10 cases of mother to child transmission). However, the study is particularly important to the administration of treatments in Africa, Asia or Eastern Europe, where there are still HIV-infected newborns and the economic situation may lead to a delay in the start of treatment. 

According to the UNAIDS report How AIDS changed everything, there were 220,000 new HIV infections in children in 2014, 190,000 of them in sub-Saharan Africa. This represents more than 600 new infections per day. The report also notes that only 42% of HIV-exposed infants received early infant diagnostic services in their first two months of life in 2013. Half of the perinatally infected children died before the age of two years due to lack of treatment, with a mortality peak located between weeks 6 and 8.

Treatment interruption 

Scientists also studied the effect of discontinuation of ART in the size of the reservoir, by tracking 3 children who temporarily suspended it, and 9 that kept it constantly. Sometimes, therapy in children may be temporarily interrupted if the patient has an undetectable viral load and a good health, thus avoiding possible toxicity. At the same time, especially when children reach adolescence, there may be a decrease in parental control or a rejection to continue therapy from the patient.

The results show that, as the ART was stopped, the reservoirs filled quickly. "This means that treatment interruptions may offset the benefits of starting therapy early after birth -explains Martínez-Picado. HIV replicates quickly in children and the faster it replicates, the greater the size of the reservoir. It is not clear the origin of viral rebound, and the expansion of the reservoirs may be irreversible".