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  IAS 2017: Conference on HIV Pathogenesis
Treatment and Prevention
Paris, France
July 23-26 2017
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HIV Viral Remission in Child with Perinatal HIV
  Viral and host characteristics of a child with perinatal HIV-1 following a prolonged period after ART cessation in the CHER trial - scroll down to see slides presented at IAS
"It's a case that raises more questions than it necessarily answers," said Linda-Gail Bekker, president of the International AIDS Society (IAS), which is holding a conference in Paris this week.
"It does raise the interesting notion that maybe treatment isn't for life. (But) it's clearly a rare phenomenon."
The child, whose name and gender were not disclosed, was part of a clinical trial in which researchers were investigating the effect of treating HIV-positive babies in the first few weeks of life, and then stopping and starting the ART medicines whilst checking whether their HIV was being controlled.
The vast majority of patients with HIV suffer an increase in the amount of the virus circulating in the body if they stop treatment, but this child was different, the South African researchers said.
Sharon Lewin, an HIV expert at the University of Melbourne and co-chair of the IAS's HIV Cure and Cancer forum, said the case threw up possible insights into how the human immune system can controls HIV replication when treatment is interrupted. Yet in terms of the scientific search for a cure for HIV and AIDS, she told Reuters, it appeared only to confirm previous reports of similarly rare cases. "We know that very rarely, people who have had treatment and stopped it are then able to control the virus."
"To our knowledge, this is the first reported case of sustained control of HIV in a child enrolled in a randomized trial of ART interruption following treatment early in infancy," said Avy Violari of the Perinatal HIV Research Unit of the University of the Witwatersrand in Johannesburg, according to The Guardian. Violari presented the case study Monday to the International AIDS Society Conference in Paris.
"Technically, this baby is not totally cured of HIV, but it is certainly what is referred to as remission, in that there's no virus circulating in the blood, and there is a normal immune system according to the range for children of their age," says Sarah Fidler, speaking on behalf of the British HIV Association toNewsweek.
Fidler says it is important that HIV-positive people do not stop taking antiretroviral drugs as a result of the case. Usually, children remain on ART throughout their life and do not stop after a set period. Fidler says the only reason the South African 9-year-old did so is because the child was part of a randomized trial.
"It is certainly not to be taken from this one person that we would then recommend that lots of people who've been treated since birth should think about stopping therapy. That's definitely not the message to be taken from one case," says Fidler, a reader and honorary consultant physician in HIV at Imperial College London.
She says that eradicating HIV transmission from mothers to children must be a global priority. About 150,000 children became infected with HIV in 2015; transmission rates from mother to child can be as high as 45 percent if pregnant women are not provided with ART. Before Monday's announcement, there had been only two documented cases of HIV-positive children going into remission after stopping ART.
Before Monday's announcement, there had been only two documented cases of HIV-positive children going into remission after stopping ART.
The Mississippi Baby
A baby girl born in Mississippi in 2010 with HIV was started on a strong course of HIV treatment hours after her mother's labor. The child did not receive any prenatal treatment and continued taking antiretrovirals until she was 18 months old. Doctors then lost track of the child, but 10 months later, she was tested again. Despite the fact she was no longer under treatment, the child showed no signs of infection with the virus.
Fidler says that the South African child's blood tests show a similar pattern to that of the so-called Mississippi baby. But after more than two years without HIV treatment, doctors confirmed in 2014 that the young girl was no longer in remission and had been restarted on ART after the virus re-emerged.
The Longest Case of HIV Remission in Children
A French girl born in 1996 contracted HIV either late in pregnancy or during the childbirth. The girl was treated for six weeks with a drug designed to stop the infection taking hold, but after the treatment was withdrawn, she suffered from high levels of HIV in her blood. The girl was then put on a course of ART for six years before coming off treatment at the age of 6.
At the International AIDS Society conference in Vancouver, British Columbia, in 2015, it was announced that the girl remained in remission 12 years after ending treatment. The girl is still thought to be in remission in what is believed to be the longest ever case of an HIV-positive child staying free of the virus after ending treatment.
Viral and host characteristics of a child with perinatal HIV-1 following a prolonged period after ART cessation in the CHER trial
Avy Violari
A. Violari1, M. Cotton2, L. Kuhn3, D. Schramm4, M. Paximadis4, S. Loubser4, S. Shalekoff4, B. da Costa Dias4, K. Otwombe1, A. Liberty1, J. McIntyre5,6, A. Babiker7, D. Gibb7, C. Tiemessen4
1University of the Witwatersrand, Perinatal HIV Research Unit, Faculty of Health Sciences, Johannesburg, South Africa, 2Stellenbosch University, Family Clinical Research Unit, Department of Paediatrics and Child Health, Stellenbosch, South Africa, 3Columbia University, Department of Epidemiology, Mailman School of Public Health, New York, United States, 4University of the Witwatersrand, Centre for HIV and STIs, National Institute for Communicable Diseases and Faculty of Health Sciences, Johannesburg, South Africa, 5Anova Health Institute, Johannesburg, South Africa, 6Univerity of Cape Town, School of Public Health & Family Medicine, Cape Town, South Africa, 7University College London, Medical Research Council, Clinical Trials Unit, London, United Kingdom
Background: In the 6-year CHER trial (2005-2011), HIV-infected infants were randomized to deferred antiretroviral therapy (ART) or early limited ART for 40 (ART-40W) or 96 (ART-96W) weeks; ART reinitiation was based on CD4 and clinical criteria. We describe a child, randomized to ART-40W in 2008, who on long term follow-up, maintains an undetectable viral load after 8.5 years off-ART.
Methods: Studies conducted to describe immunological and viral characteristics included: ultrasensitive qualitative nested and quantitative semi-nested PCR assay to assess HIV DNA reservoir; co-culture of CD4 cells with MOLT-4/CCR5 and CD8-depleted phytohaemagglutinin-activated lymphocytes to detect replication-competent virus.
Results: HIV diagnosis was confirmed by HIV-DNA PCR+ at age 32 days, and on days 39 and 60, VL was >750,000 and 151,000 copies/ml respectively. ART started at age 8.7 weeks and was interrupted at 40 weeks post randomisation. On ART, VL declined to < 50copies/ml at week 24 and was < 20 copies/ml post-interruption .During later follow-up 6-monthly VLwere also < 20copies/ml. At age 9.5 years, the child was clinically asymptomatic with CD4 802 cells/μl. Qualitative DNA PCR was negative. HIV-antibody by ELISA was negative but was weakly reactive to Gag p40 and p24 on Western blot; a weak Gag-specific CD4 T-cell response was detected by whole blood intracellular cytokine assay. Proviral DNA was positive by ultrasensitive nested (int) PCR and HIV DNA reservoir size was estimated at 2.2 copies/106 PBMCs by semi-nested quantitative (RT) assay. DNA sequencing of Gag confirmed subtype-C virus. No replication-competent virus was detected in culture supernatants by day 22 using p24 ELISA and ultrasensitive nested RT-PCR. All HLA loci were heterozygoous (A*30:02:01/66:01; B*08:01:01/44:03:01; C*04:01:01/07:01:01; DRB1*12:01:01/13:02:01; DPB1*01:01:01/18:01; B1*05:01:01/06:09:01). The KIRAA1 genotype included both full-length and truncated KIR2DS4. Immunophenotyping showed few CCR5-expressing CD4 T-cells (6.6%), low CCR5 density, low immune activation (HLA-DR, TIGIT), high PD-1expression and high % naive CD8 T-cells.
Conclusions: To our knowledge, this is the first case of sustained virological control from a randomized trial of ART interruption following early treatment of infants. Further investigation may expand our understanding of how the immune system controls HIV replication and inform future research strategies for ART interruption after early ART.