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Recent progress in anti-HIV broadly neutralizing antibody research

Tobin, Stacey C.

doi: 10.1097/QAD.0000000000001544
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The Tobin Touch, Inc., Arlington Heights, Illinois, USA.

Correspondence to Stacey C. Tobin, PhD, ELS, The Tobin Touch, Inc., Arlington Heights, Illinois, USA. E-mail: stacey.tobin@thetobintouch.com

Received 5 May, 2017

Accepted 9 May, 2017

Passive immunization with broadly neutralizing anti-HIV antibodies (bNAbs) holds promise for preventing HIV infection and transmission. In a study in macaques, Gautam et al.[1] recently reported that a single prophylactic injection of four anti-HIV bNAbs protected against 23 weekly challenges of simian HIV (SHIV) compared with untreated controls, which required only two to six challenges for infection. The antibodies VRC01 and 3BNC117 target the CD4+ binding site on gp120, whereas, 10–1074 targets the gp120 N332 glycan. A derivative of VRC01 with a longer half-life, VRC01-LS, prolonged protection from SHIV infection to 14.5 weeks, compared with 8 weeks with VCR01. The authors concluded that combinations of anti-HIV bNAbs engineered to increase half-life may provide durable protection against HIV infection in individuals at high risk of exposure.

Another recent report by Bar et al.[2] examined the ability of multiple infusions of the anti-HIV bNAb VRC01 to eradicate viral reservoirs in individuals with HIV infection well controlled with antiretroviral therapy (ART). Two open-label trials [AIDS Clinical Trials Group (ACTG) A5340 and National Institutes of Health (NIH) 15-I-0140] included a total of 24 participants who received VRC01 before or after ART discontinuation and then continued receiving periodic infusions with monitoring of viral load. ART was reinitiated upon viral load rebound. No severe adverse events were noted in either trial, and CD4+ cell counts did not decrease below 350 cells/μl in any participant. The median times to viral suppression after reinitiation of ART were 6 and 8 weeks in the ACTG and NIH trials, respectively.

In both trials, multiple infusions of VRC01 led to high plasma antibody concentrations, but did not sustain suppression of viremia. In the ACTG trial, the median time to viral rebound (>200 copies/ml) was 4 weeks, and in the NIH trial, the median time to rebound (>40 copies/ml) was 39 days. Compared with historical controls from previous trials of ART discontinuation, 38% of ACTG participants had viral suppression at week 4 (vs. 13%; P = 0.04). The response was higher in the NIH trial, in which 80% of participants had viral suppression at week 4 (vs. 13% for historical controls; P < 0.001).

Bar et al. also found that VRC01 selected for resistant virus and that most participants had some baseline resistance to VRC01. The authors suggested that this ‘archived resistance’ to VRC01 may be greater in individuals with chronic infection, and that use of the bNAbs may require resistance prescreening. The authors also proposed that combinations of bNAbs that target various sites on the HIV envelope might show greater efficacy.

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Acknowledgements

Conflicts of interest

There are no conflicts of interest.

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References

1. Gautam R, Nishimura Y, Pegu A, Nason MC, Klein F, Gazumyan A, et al. A single injection of anti-HIV-1 antibodies protects against repeated SHIV challenges. Nature 2016; 533:105–109.
2. Bar KJ, Sneller MC, Harrison LJ, Justement JS, Overton ET, Petrone ME, et al. Effect of HIV antibody VRC01 on viral rebound after treatment interruption. N Engl J Med 2016; 375:2037–2050.
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