Recent Advances in HIV Treatment

By: Jenny Park PharmD Candidate c/o 2015

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A series of broad HIV specific monoclonal antibodies (mAb) have been isolated and been shown to bind to CD4 binding sites, V1/V2 loops, V3/V4 loops, glycans, and proximal external regions. It has been shown that administration of a “cocktail” of HIV-1 specific monoclonal antibodies along with single glycan dependent mAb PGT121 resulted in decline of viral plasma to undetectable levels in monkeys that were infected with Simian HIV (SHIV).¹

Two research centers, The Harvard Medical School and the National Institute of Allergy and Infectious Diseases, evaluated the therapeutic potential of broad and potent HIV-1 specific mAbs in primates with an intact immune system. The teams worked with monkeys infected with a monkey-human hybrid version of HIV known as Simian HIV (SHIV). SHIV is an engineered virus that contains HIV and SIV and is used in animal models.² Researchers infused combinations of mAbs into rhesus macaques, also known as Nazuri monkeys. These monkeys all exhibited viral loads of 3.4–4.9 log RNA copies/mL along with disease progression and reduced CD4+ T lymphocyte counts.²

It was shown that a single mAb infusion had up to a 3.1 log decline of plasma viral RNA in seven days and also reduced proviral DNA in peripheral blood, gastrointestinal mucosa, and lymph nodes without the development of viral resistance.² Following the initial mAb infusion, there was a rapid decline of plasma viral loads to undetectable levels by day seven in all of the monkeys. Viral control lasted for 84 to 98 days in two of the monkeys. One monkey had viral replication control until day 98 while another monkey exhibited long term viral control for over 200 days despite the absence of detectable serum antibodies after day 70. It was also shown that proviral DNA in peripheral blood declined by ten fold in the monkeys that received antibody therapy. ³  After the antibody infusion, there was also an increase in host virus specific neutralizing antibody activity as and improved T lymphocyte responses. The National Institute of Allergy and Infectious Diseases obtained similar results to that of the Harvard Medical Team.

However, given the differences between SHIV-infected rhesus monkeys and HIV-1 infected humans, clinical trials are required to establish the therapeutic efficacy of potent neutralizing HIV-1 specific mAbs in human. The idea of shifting the standard of care for HIV patients from their current daily multiple pill burdens to periodic injections has the potential to revolutionize care for this population. However, nothing can be proven until what has been seen in these studies holds true in human beings. As said by Dr. Collins, Director of NIH, “If we could convince the immune system to develop these antibodies routinely, then we’d really have something.”⁴ 

SOURCES:

1. Barouch DH, Whitney JB, Moldt B, et al. Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys. Nature. 2013;503(7475):224-8.
2. Joag SV, Li Z, Foresman L, et al. Chimeric simian/human immunodeficiency virus that causes progressive loss of CD4+ T cells and AIDS in pig-tailed macaques. J Virol. 1996;70(5):3189-97.
3. Prengaman, Kate. (2013, Nov 1). New HIV antibodies show potential. ARS technical. Retrieved February 18,2014 from http://arstechnica.com/science/2013/11/new-hiv-antibodies-show-potential/

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