Ceasing treatment may be the only way to determine whether HIV is cured, but doing so carries long-term risks.
Following the success of recent cases in Mississippi and California where infants were functionally cured of HIV
following early combination treatment, a study finds that while the virus may be reduced to undetectable levels, the disease could be reactivated if treatment stops.
The study, published online June 9, 2014, in Clinical Infectious Diseases, examined 136 infants, born to mothers infected with HIV-1, who received combination antiretroviral therapy (cART) within 72 hours of birth. The researchers focused on 12 of those children who were confirmed to be infected with HIV.
Of the 12 children, 4 achieved sustained virologic suppression. Six children did not achieve sustained virologic response due to poor adherence to cART from the outset of treatment. Two of the children were able to maintain an undetectable viral load for 2 to 3 years, but the disease subsequently rebounded due to nonadherence.
Of the 4 infants who achieved sustained virologic suppression, all were started on a treatment regimen of zidovudine, lamivudine, and nevirapine within 24 hours of birth. Because the 4 infants tested positive for HIV within the first 48 hours of life and had a low but detectable viral load during the first few weeks of life, researchers suggest that the children were likely infected with the virus in utero close to the time of delivery.
Suppression of the virus was initially documented between 66 and 189 days of life. The 4 infants have since remained on the same cART treatment regimen and are clinically well with normal T-cell counts.
“The absence of HIV-1-specific humoral and cell-mediated immune responses in our four children is likely a consequence of rapid virologic control by cART and lack of development of a mature B- and T-cell response to HIV-1,” the study authors wrote. “It has previously been shown that the majority of children initiating cART within three months of birth become seronegative by approximately 16 months of age and that the kinetics of antibody titer decline in these children is similar to that observed with passive maternal antibody in HIV-1 uninfected infants.”
The researchers noted that T-cell responses remained negative or reverted to negative during the first 6 months of life in infants who started effective cART therapy. However, the study finds that minute amounts of the virus can still be reactivated from the peripheral blood of children who achieved sustained virologic suppression from early cART therapy.
Of the 4 infants with no detectable signs of the virus, 3 carried genetic markers associated with superior HIV control in adults, which suggests contributions from the mother or child’s immune system toward virologic control in children infected perinatally.
Despite the promising results of an early cART regimen in reducing the viral load to undetectable levels, the researchers note that a structured treatment interruption may be the only method to determine if the virus has been eradicated and if a functional cure can be achieved. The potential rebound of the virus carries significant risk because resistance to cART has been previously observed in adults and the rebound could create an expansion of the HIV reservoir, which would make future treatment of the disease more difficult.
“These findings have important implications for HIV cure research in perinatally infected children, as it may not be feasible to obtain sufficient numbers of peripheral blood mononuclear cells to reasonably exclude the presence of replication competent virus,” the authors wrote.