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Published on: December 23, 2016
Impact of Delayed Early Antiretroviral Therapy Initiation on Treatment Outcomes in Infant Macaques Exposed to SHIVAD8
Li Ma1, Yoshiaki Nishimura2, Xueling Wu3
1Tulane National Primate Research Center, Tulane University School of Medicine, 18703 Three Rivers Road, Covington, LA 70433, USA.
Insights
Starting antiretroviral therapy later in HIV-exposed infants reduced virologic remission rates. Early intervention is crucial for controlling pediatric HIV, even in the absence of detectable immune responses.
Area of Science:
- Immunology
- Virology
- Pediatric Infectious Diseases
Background:
- Infants born to mothers with human immunodeficiency virus (HIV) face significant risks of acquiring the virus.
- Even with maternal antiretroviral therapy, C-section, and formula feeding, transmission can occur.
- Previous research indicated that initiating antiretroviral treatment at three days post-SIV infection achieved 80% pediatric virologic remission.
Purpose of the Study:
- To investigate treatment outcomes in simian-human immunodeficiency virus (SHIV)-exposed infant macaques with a two-day delay in early intervention.
- To explore the mechanisms behind virologic control in these infants.
- To assess the impact of delayed treatment initiation on sustained virologic remission.
Main Methods:
- Infant macaques were exposed to SHIV postnatally.
- Antiretroviral treatment was initiated five days post-exposure.
- Viral replication and immune responses (neutralizing antibodies, cytotoxic T cells, ADCC) were monitored.
- Analytical treatment interruption was performed to assess sustained virologic remission.
Main Results:
- Initiating treatment at five days post-exposure suppressed viral replication.
- Only one of three infant macaques achieved sustained virologic remission after treatment interruption.
- The infant with sustained remission showed no detectable virus-specific immunity.
- Delayed treatment initiation significantly reduced the rate of sustained virologic remission compared to earlier intervention.
Conclusions:
- Early antiretroviral treatment initiation is critical for achieving sustained virologic control in HIV-exposed, infected infants.
- Delayed intervention, even by two days, can compromise long-term remission.
- Virologic control may be achieved without robust virus-specific immune responses, emphasizing the primacy of early treatment.
Abstract:
Infants born to HIV-positive mothers remain at significant risk of HIV acquisition despite maternal adherence to antiretroviral therapy, cesarean delivery, and formula feeding. Our previous study reported that initiating early antiretroviral treatment at three days post-SIV infection resulted in approximately eighty percent of pediatric virologic remission. In this study, we investigated treatment outcomes in postnatally SHIV-exposed infant macaques when early intervention was delayed by two days, as well as the mechanisms underlying virologic control. The results showed that, although initiating treatment at five days post-exposure effectively suppressed viral replication, only one of the three infant macaques achieved a sustained state of virologic remission following analytical treatment interruption. Notably, this virus-controlled infant lacked detectable virus-specific immunity, including neutralizing antibodies, cytotoxic T cell responses, and antibody-dependent cellular cytotoxicity. These findings highlight the critical importance of early treatment initiation as a key determinant of virologic control in HIV-exposed, infected infants. This study provides valuable insights for guiding early pediatric HIV intervention strategies in clinical settings.
