Inactivation of human immunodeficiency virus type 1 by nonoxynol-9, C31G, or an alkyl sulfate, sodium dodecyl sulfate

A highly desirable approach to prevention of human immunodeficiency virus t ype 1 (HIV-1) transmission during sexual intercourse is the development of nontoxic, topical, broad spectrum microbicides effective against transmissi on of cell-associated and cell-free virus. Toward this end, the HIV-I inact ivation potential of surface active agents C31G and an alkyl sulfate, sodiu m dodecyl sulfate (SDS) was assessed. Because of its extensive use as a mic robicidal agent, nonoxynol-9 (N-9) was used as a reference against which C3 1G and SDS were compared. Viral inactivation was measured using HIV-I LTR-b eta-galactosidase indicator cells (expressing CD4 or CD4/CCR5) derived from HeLa cells, a cell line of human cervical adenocarcinoma origin. In experi ments which examined inactivation of cell-free HIV-I, C31G was generally mo re effective than N-9. Viral inactivation by SDS occurred at twice the conc entration necessary to achieve similar levels of inactivation using either N-9 or C31G. Using HeLa and HeLa-derived cells in cytotoxicity studies, it was demonstrated that SDS is as much as 11 and five times less cytotoxic th an N-9 or C31G, respectively, during 48 h of continuous exposure. SDS (unli ke C31G and N-9) can inactivate non-enveloped viruses such as human papillo mavirus (HPV) [Howett, M.K., Neely, E.B., Christensen, N.D., Wigdahl, B., K rebs, F.C., Malamud, D., Patrick, S.D., Pickel, M.D., Welsh, P.A., Reed, C. A., Ward, M.G., Budgeon, L.R., Kreider, J.W., 1999. A. broad-spectrum micro bicide with virucidal activity against sexually transmitted viruses. Antimi crob. Agents Chemother. 43(2), 314-321]. Since addition of SDS to C31G or N -9 may make the resulting microbicidal mixtures broadly effective against b oth enveloped and non-enveloped viruses, several surface active agent combi nations were evaluated for their abilities to inactivate HIV-I. Addition of SDS to either C31G or N-9 resulted in mixtures that were only slightly les s effective than equivalent concentrations of C31G or N-9 alone. To investi gate inactivation of cell-associated infectivity, HIV-I IIIB-infected SupT1 cells were treated with N-9, C31G, or SDS. Inactivation of cell-associated infectivity required higher microbicide concentrations than were needed fo r inactivation of cell-free virus. However, the relative activities of N-9, C31G, or SDS were similar to those seen in assays of inactivation using ce ll-free virus. These studies suggest that C31G and SDS may be attractive ca ndidates for human trials as topical microbicides effective against HIV-1 t ransmission since bath function at concentrations that provide effective vi ral inactivation with low levels of cytotoxicity. SDS microbicides (used al one or with other microbicides) may provide the added advantage of protecti on from HPV infection. (C) 1999 Elsevier Science B.V. All rights reserved.