Progress in HIV Research in October 2018 (II)

(…Continued)

 

  • JCI: Infectious HIV is not present in liver macrophages of HIV-infected patients receiving treatment

doi:10.1172/JCI121678

 

In a new study, researchers from Johns Hopkins University and Los Alamos National Laboratory determined whether liver macrophages are infectious HIV-1 virus pools after ART treatment. The real source of the liver tissue samples from nine HIV-1 infected individuals (7 of them were transplanted at Johns Hopkins Hospital). Eight of these nine patients received ART treatment from 8 months to 140 months. The results of the study were published in the Journal of Clinical Investigation, entitled “No recovery of replication-competent HIV-1 from human liver macrophages.” The author of the paper is Dr. Ashwin Balagopal, associate professor of infectious diseases at Johns Hopkins University School of Medicine.

 

Using laboratory techniques to measure HIV-1 containing T cells and isolate liver macrophages, the researchers found that HIV-1 is still present in these macrophages even after prolonged exposure to the virus-inhibiting ART. However, Balagopal said that when his team tried to simulate a virus “rebound” in liver macrophages in the lab, they only found “a small amount of HIV-1 fragments, no strong growth of full-length infectious virus”.

 

The researchers found that HIV-1 is present in liver macrophages of a subject who has been treated for ART for 11.7 years. They concluded that although patients with long-term ART treatment, liver macrophages may carry HIV-1 for a long time, the virus cannot continue to be infected by itself, nor can it play the role of HIV-1 virus pool. This is because it cannot be copied.

 

  • Cell: How HIV stimulates innate immune activation

doi:10.1016/j.cell.2018.08.062

 

Protective antiviral immunity can be induced by detection of the virus by an innate immune sensor. The viral DNA sensor, GMP-AMP synthase (cGAS), is required for human dendritic cells and macrophages to detect HIV.

 

However, the synthesis of HIV DNA during infection is not sufficient for immune activation. Capsid proteins that bind to viral DNA play a key role in promoting cGAS-mediated immune activation.

 

Recently, researchers from France found that NONO is an important sensor for HIV capsids in the nucleus. Compared to highly pathogenic HIV-1, NONO protein has a higher affinity for direct binding of the weakly pathogenic HIV-2 capsid. After HIV infection, NONO is critical for cGAS activation, which is linked to HIV and cGAS and to HIV DNA in the nucleus. NONO recognizes conserved regions in the HIV capsid and has limited tolerance to escape mutations.

 

Detection of nuclear viral capsids by NONO to promote DNA sensing of cGAS reveals an innate strategy for achieving virus-to-self differentiation in the nucleus.

 

  • Int J Oral Max Surg: Evaluation of implant survival in HIV-positive patients

doi:10.1016/j.ijom.2018.01.009

 

 

Currently, there is no consensus on the use of implants in human immunodeficiency virus (HIV)-positive patients. This study assessed the survival and success rate of implants in HIV-positive patients, marginal bone resorption and complications.

 

The review was conducted in accordance with the PRISMA checklist. Two independent reviewers conducted a comprehensive search of the PubMed/MEDLINE, Scopus and Cochrane library databases to publish the study by October 2017. Six studies were selected for review.

 

A total of 821 implants were placed: 493 implants were implanted in 169 HIV-positive patients and 328 implants were placed in 135 HIV-negative patients. The average follow-up time was 47.9 months. Calculate the weighted mean survival, success rate, and marginal bone resorption values of HIV-positive patients. The average survival rate and success rate at the patient level (according to the number of patients) were 94.76% and 93.81%, respectively; when calculating the implant level (according to the number of implants), these ratios were 94.53% and 90.37%, respectively. The mean marginal bone resorption was 0.83 mm at the patient level and 0.99 mm at the implant level. Therefore, the implant is suitable for HIV-positive patients with a controlled risk factor and rehabilitation of normal CD4+ cell counts.

 

  • AIDS: The liver of HIV-positive people is safely transplanted to patients for the first time

doi:10.1097/QAD.0000000000002000

 

 

A child with an advanced liver disease cannot survive without a liver transplant. To this end, South African doctors transplanted part of the liver of her HIV-positive mother to the HIV-negative child. The child and her mother were in good condition for a year after the transplant, and the child may not be infected with HIV. The results of the study were published in the AIDS journal, entitled “Living donor liver transplant from an HIV-positive mother to her HIV-negative child: opening up new therapeutic options”.

 

  • A major breakthrough in HIV treatment! You don’t have to take it every day, just inject it once a month and 12 times a year!

News source: ViiV Healthcare presents three-year data for investigational long-acting injectable, two-drug HIV regimen

 

ViiV Healthcare is an HIV/AIDS drug development company owned by GlaxoSmithKline (GSK), Pfizer and Shionogi. Recently, the company published a monthly injection of long-acting HIV therapy in the cabotegravir/rilpivirine (CAB/RPV) Phase II clinical study LATTE-2 for up to 3 years (160 weeks).

 

LATTE-2 is a multi-center, parallel-group, open-label Phase IIb study enrolled in patients with antiretroviral therapy (ART) who are initially infected with HIV and designed to evaluate the efficacy and safety of virus inhibition of long-acting injection therapy with CAB/RPV treatment regimen (once every 4 weeks [Q4W], once every 8 weeks [Q8W]) compared with the 3-drug oral ART regimen (CAB 30mg + ABC / 3TC [abacavir / lamivudine]). In the study, patients who received a 3-dose oral ART regimen for virological suppression (plasma HIV-1 RNA <50 copies/ml) during the 20-week induction period (IP) were randomized to a maintenance phase (MP) of 2:2:1. The patients were assigned CAB/RPV Q4W (intramuscular injection once every 4 weeks), CAB/RPV Q8W (intramuscular injection once every 8 weeks), and continued to receive 3 oral administration of ART regimen. After 96 weeks, patients who continued to receive 3-medical oral ART regimen during the maintenance phase entered the extended phase and were treated with the CAB/RPV Q8W regimen or the CAB/RPV Q4W regimen.

 

Data show that at week 160, 90% (n = 104/115) and 83% (n = 95/115) of patients receiving CAB/RPV Q8W regimen and CAB/RPV Q4W regimen maintained virological suppression. In addition, patients who switched to the CAB/RPV Q8W regimen and the CAB/RPV Q4W regimen from week 96 had 97% (n=33/34) and 100% (n=10/10) virological suppression rate at week 160, respectively. At 48 weeks prior to treatment, 2 patients had a clinical protocol-defined virological failure (PVDF) in the CAB/RPV Q8W regimen, 1 of which was a therapeutically produced non-nucleoside reverse transcriptase inhibitor (NNRTI) and an integrase inhibitor (INI) resistance. No additional PVDF cases were observed in each treatment group from week 48 to week 160.

 

During the 160 weeks of treatment, most patients reported an injection site response (ISR), of which 85% were mild, 14% were moderate, and 87% of ISR was resolved within 7 days. In addition to ISR, the most common adverse events were nasopharyngitis (38%), diarrhea (22%), and headache (22%). In the Q8W and Q4W treatment groups, 3% and 10% of patients discontinued due to adverse events, and only 3 (n=274) discontinued due to ISR.

 

 

Reference:

Erica N. Borducchi, Jinyan Liu, Joseph P. Nkolola et al. Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys. Nature, Published Online: 03 October 2018, doi:10.1038/s41586-018-0600-6.

M.Uzzan el al. Anti-a4ß7 therapy targets lymphoid aggregates in the gastrointestinal tract of HIV-1–infected individuals. Science Translational Medicine (2018), doi:10.1126/scitranslmed.aau4711.

Martina Kovarova, S. Rahima Benhabbour, Ivana Massud, et al. Ultra-long-acting removable drug delivery system for HIV treatment and prevention, Nature Communications (2018). DOI: 10.1038/s41467-018-06490-w.

Abraham J. Kandathil, Sho Sugawara, Ashish Goyal et al. No recovery of replication-competent HIV-1 from human liver macrophages. Journal of Clinical Investigation, 1 October 2018, 128(10):4501-4509, doi:10.1172/JCI121678.

Lahaye X et al. NONO Detects the Nuclear HIV Capsid to Promote cGAS-Mediated Innate Immune Activation. CELL 2018, DOI: 10.1016/j.cell.2018.08.062.

T.Makiguchi,et al. Standard morphology of the oral commissure and changes resulting from reconstruction for defects involving the commissure. International Journal of Oral and Maxillofacial Surgery. 2018 October. Doi:10.1016/j.ijom.2018.01.009.

Botha J, Conradie F, Etheredge H, et al. Living donor liver transplant from an HIV-positive mother to her HIV-negative child: opening up new therapeutic options. AIDS. 2018 Oct 23;32(16): F13-F19. doi: 10.1097/QAD.0000000000002000.

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