Animal Models of HIV Transmission Through Breastfeeding and Pediatric HIV Infection

Rompay, Koen K. A. Van; Jayashankar, Kartika

doi:10.1007/978-1-4614-2251-8_7

Cited by 6 publications

(4 citation statements)

References 141 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Six infant RMs were orally challenged with SHIV.CH505.375H.dCT (22) by bottle feeding 3 times/day for 5 days at a dose of 8.5 ϫ 10 4 50% tissue culture infective doses (TCID 50 ) to mimic breast milk transmission. After a week of challenge, only 1 infant became infected, which is not surprising, considering the low rate of natural transmission in macaques during breast-feeding (24,25). To have better control over the challenge dosage and the timing of infection, the remaining 5 RMs were sedated and orally challenged weekly at a dose of 6.8 ϫ 10 5 TCID 50 .…”

Section: Kinetics Of Shivch505375hdct Replication In Orally Infectmentioning

confidence: 99%

Analytical Treatment Interruption after Short-Term Antiretroviral Therapy in a Postnatally Simian-Human Immunodeficiency Virus-Infected Infant Rhesus Macaque Model

Goswami

Nelson

et al. 2019

mBio

Self Cite

View full text Add to dashboard Cite

To achieve long-term viral remission in human immunodeficiency virus (HIV)-infected children, novel strategies beyond early antiretroviral therapy (ART) will be necessary. Identifying clinical predictors of the time to viral rebound upon ART interruption will streamline the development of novel therapeutic strategies and accelerate their evaluation in clinical trials. However, identification of these biomarkers is logistically challenging in infants, due to sampling limitations and the potential risks of treatment interruption. To facilitate the identification of biomarkers predicting viral rebound, we have developed an infant rhesus macaque (RM) model of oral simian-human immunodeficiency virus (SHIV) SHIV.CH505.375H.dCT challenge and analytical treatment interruption (ATI) after short-term ART. We used this model to characterize SHIV replication kinetics and virus-specific immune responses during short-term ART or after ATI and demonstrated plasma viral rebound in 5 out of 6 (83%) infants. We observed a decline in humoral immune responses and partial dampening of systemic immune activation upon initiation of ART in these infants. Furthermore, we monitored SHIV replication and rebound kinetics in infant and adult RMs and found that both infants and adults demonstrated equally potent virus-specific humoral immune responses. Finally, we validated our models by confirming a well-established correlate of the time to viral rebound, namely, the pre-ART plasma viral load, as well as identified additional potential humoral immune correlates. Thus, this model of infant ART and viral rebound can be used and further optimized to define biomarkers of viral rebound following long-term ART as well as to preclinically assess novel therapies to achieve a pediatric HIV functional cure. IMPORTANCE Novel interventions that do not rely on daily adherence to ART are needed to achieve sustained viral remission for perinatally infected children, who currently rely on lifelong ART. Considering the risks and expense associated with ART interruption trials, the identification of biomarkers of viral rebound will prioritize promising therapeutic intervention strategies, including anti-HIV Env protein therapeutics. However, comprehensive studies to identify those biomarkers are logistically challenging in human infants, demanding the need for relevant nonhuman primate models of HIV rebound. In this study, we developed an infant RM model of oral infection with simian-human immunodeficiency virus expressing clade C HIV Env and short-term ART followed by ATI, longitudinally characterizing the immune responses to viral infection during ART and after ATI. Additionally, we compared this infant RM model to an analogous adult RM rebound model and identified virologic and immunologic correlates of the time to viral rebound after ATI.

show abstract

Section: Kinetics Of Shivch505375hdct Replication In Orally Infectmentioning

confidence: 99%

Analytical Treatment Interruption after Short-Term Antiretroviral Therapy in a Postnatally Simian-Human Immunodeficiency Virus-Infected Infant Rhesus Macaque Model

Goswami

Nelson

et al. 2019

mBio

Self Cite

View full text Add to dashboard Cite

show abstract

“…Experimental SIV/SHIV infection of rhesus macaques recapitulates many relevant features of HIV transmission in humans, including MTCT, and can thus serve as a relevant model to study early virus-host interactions. 10 In this study, we evaluated how oral exposure to immunodeficiency virus drives viral infection and dissemination, and establishment of the viral reservoir in infants. The oral and esophageal mucosa, as well as the tonsils were identified as primary entry sites in a previous study.…”

Section: Introductionmentioning

confidence: 99%

Early Sites of Virus Replication After Oral SIV_mac251 Infection of Infant Macaques: Implications for Pathogenesis

Amedee

Phillips

Jensen

et al. 2018

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

Despite optimization of preventative measures for vertical HIV-1 transmission, daily, roughly 400 infants become HIV infected, most of them through breastfeeding. Viral entry has been presumed to occur in the gastrointestinal tract; however, the exact entry site(s) have not been defined. Therefore, we quantified simian immunodeficiency virus (SIV) RNA and DNA in oral, intestinal, and systemic tissues of 15 infant macaques within 48-96 h after oral SIV exposure. SIV DNA was detected as early as 48 h, whereas SIV RNA was typically detected at later time points (72-96 h). Transmitted founder viruses were identical or very similar to a single genotype in the SIV challenge stock. SIV RNA and DNA were most frequently found in lymph nodes (LNs) draining the oral cavity and in the ileum. Using in situ hybridization, SIV-infected cells in LNs were exclusively represented by CD3 T cells. SIV RNA and DNA were also detected in the lungs of 20% of the animals, and 60% of the animals had detectable SIV DNA in the cerebrum. The early detection of viral RNA or DNA in lung and brain tissues emphasizes the need for early treatment of pediatric HIV infection to prevent damage not only to the immune system but also to the respiratory tract and central nervous system.

show abstract

“…In 2009, an estimated 370,000 infants contracted HIV infection during the perinatal and breastfeeding period [6, 7]. AIDS related deaths are decreasing globally mainly due to the increased availability of highly active antiretroviral therapy (HAART) as well as care and support for people living with HIV/AIDS [8, 9].…”

Section: Introductionmentioning

confidence: 99%

Comparison of auditory brainstem response in HIV-1 exposed and unexposed newborns and correlation with the maternal viral load and CD4+ cell counts

Fasunla¹,

Ogunbosi

Odaibo

et al. 2014

Aids

View full text Add to dashboard Cite

Objective The effects of maternal HIV infection and antiretroviral therapy on hearing of HIV-exposed newborns in sub-Saharan Africa have not been investigated. We determined the prevalence of sensorineural hearing loss among HIV-exposed newborns and the association between the hearing threshold and maternal & newborn parameters. Design A cohort audiometric study of newborns between October 2012 and April 2013. Settings Secondary and tertiary hospital based study. Participants Consecutive 126 HIV-exposed and 121 HIV-unexposed newborns. Intervention Hearing screening of the newborns were done with Auditory Brainstem Response and compared with maternal HAART, CD4 cell counts, RNA viral loads and newborn CD4 percent. Main outcome measure Hearing threshold levels of both groups were measured and analyzed. Results 11.1% of HIV-exposed and 6.6% of unexposed newborns had hearing impairment (p=0.2214). 6.4% of HIV-exposed and 2.5% HIV-unexposed newborns had hearing threshold >20dBHL (p = 0.1578). There was no significant association between the hearing thresholds of HIV-exposed newborns and maternal CD4 cell counts (p = 0.059) but there was with maternal viral load (p=0.034). There was significant difference between the hearing thresholds of HIV-exposed newborns with CD4 % of ≤25 and >25. This study showed significant difference in the hearing of the 119 HAART-exposed newborns and 7 unexposed newborns (p=0.002; RR=0.13 [0.05–0.32]). Conclusion There was a trend towards more hearing loss in HIV-exposed newborns. However, hearing thresholds increase with increasing mothers’ viral load. This background information supports the need for further studies on the role of in-utero exposure to HIV and HAART in newborn hearing loss.

show abstract

Animal Models of HIV Transmission Through Breastfeeding and Pediatric HIV Infection

Cited by 6 publications

References 141 publications

Analytical Treatment Interruption after Short-Term Antiretroviral Therapy in a Postnatally Simian-Human Immunodeficiency Virus-Infected Infant Rhesus Macaque Model

Analytical Treatment Interruption after Short-Term Antiretroviral Therapy in a Postnatally Simian-Human Immunodeficiency Virus-Infected Infant Rhesus Macaque Model

Early Sites of Virus Replication After Oral SIV_mac251 Infection of Infant Macaques: Implications for Pathogenesis

Comparison of auditory brainstem response in HIV-1 exposed and unexposed newborns and correlation with the maternal viral load and CD4+ cell counts

Contact Info

Product

Resources

About

Animal Models of HIV Transmission Through Breastfeeding and Pediatric HIV Infection

Cited by 6 publications

References 141 publications

Analytical Treatment Interruption after Short-Term Antiretroviral Therapy in a Postnatally Simian-Human Immunodeficiency Virus-Infected Infant Rhesus Macaque Model

Analytical Treatment Interruption after Short-Term Antiretroviral Therapy in a Postnatally Simian-Human Immunodeficiency Virus-Infected Infant Rhesus Macaque Model

Early Sites of Virus Replication After Oral SIVmac251 Infection of Infant Macaques: Implications for Pathogenesis

Comparison of auditory brainstem response in HIV-1 exposed and unexposed newborns and correlation with the maternal viral load and CD4+ cell counts

Contact Info

Product

Resources

About

Early Sites of Virus Replication After Oral SIV_mac251 Infection of Infant Macaques: Implications for Pathogenesis