Beschreibung:
<jats:sec>
<jats:title>Objective:</jats:title>
<jats:p>The opioid epidemic has increased parentally acquired HIV infection. To inform the development of a long-acting prevention strategy, we evaluated the protective efficacy of broadly neutralizing antibodies (bNAbs) against intravenous simian-human immunodeficiency virus (SHIV) infection in macaques.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Design:</jats:title>
<jats:p>Five cynomolgus macaques were injected once subcutaneously with 10-1074 and 3BNC117 (10 mg each kg<jats:sup>−1</jats:sup>) and were repeatedly challenged intravenously once weekly with SHIV<jats:sub>AD8-EO</jats:sub> (130 TCID<jats:sub>50</jats:sub>), until infection was confirmed via plasma viral load assay. Two control macaques, which received no antibody, were challenged identically.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Methods:</jats:title>
<jats:p>Plasma viremia was monitored via RT-qPCR assay. bNAb concentrations were determined longitudinally in plasma samples via TZM-bl neutralization assays using virions pseudotyped with 10-1074-sensitive (X2088_c9) or 3BNC117-sensitive (Q769.d22) HIV envelope proteins.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results:</jats:title>
<jats:p>Passively immunized macaques were protected against a median of five weekly intravenous SHIV challenges, as compared to untreated controls, which were infected following a single challenge. Of the two bNAbs, 10-1074 exhibited relatively longer persistence <jats:italic toggle="yes">in vivo</jats:italic>. The median plasma level of 10-1074 at SHIV breakthrough was 1.1 μg ml<jats:sup>−1</jats:sup> (range: 0.6–1.6 μg ml<jats:sup>−1</jats:sup>), whereas 3BNC117 was undetectable. Probit modeling estimated that 6.6 μg ml<jats:sup>−1</jats:sup> of 10-1074 in plasma corresponded to a 99% reduction in per-challenge infection probability, as compared to controls.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusions:</jats:title>
<jats:p>Significant protection against repeated intravenous SHIV challenges was observed following administration of 10-1074 and 3BNC117 and was due primarily to 10-1074. Our findings extend preclinical studies of bNAb-mediated protection against mucosal SHIV acquisition and support the possibility that intermittent subcutaneous injections of 10-1074 could serve as long-acting preexposure prophylaxis for persons who inject drugs.</jats:p>
</jats:sec>