Masking the envelope complex to prevent membrane attachment seems to be a simple mechanism to prevent viral entry. The blockade of CD4 and V3-loop antibody binding by mHSA supports this hypothesis. The masking by mHSA completely inhibited rCD4 binding and partially inhibited the V3-loop antibody binding, indicating that a large and important proportion of the gp120 molecule is masked by mHSA. The surface of gp120 is per se covered by complex carbohydrate structures, which represent more than 55% of the gp120 molecular weight. Especially the elimination of the carbohydrate structure g15 within the V3 loop plays an important role in viral entry and these mutants showed higher infectivity. Due to higher infectivity, these viruses can escape from neutralizing antibodies present in human sera [23] . An interesting advantage of mHSA is the ability to neutralize these antibody resistant viruses. A more efficient neutralization of such viruses by mHSA might be the result of the lack of N-glycan g15 that renders the V3 loop more exposed. Such an unmasked V3 loop seems to be a better binding target for HOCl-modified albumins since the binding of V3-loop-specific neutralizing antibodies was blocked by mHSA. Masking the CD4 and V3 loop area by mHSA was also efficient for the blockade of CCR5-specific infection, but 3 times higher levels were necessary compared to the neutralization of CXCR4-viruses. Thus, V3-driven selection for higher infectivity of CXCR4 viruses or the switch from CCR5-to CXCR4-usage is not beneficial for promoting escape from mHSA neutralization. Blocking both coreceptor pathways is an important step to block HIV-1 transmission. In an evolving epidemic, CXCR4-tropism is present in high frequency among all HIV-1 subtypes except subtype C [24, 25] . The high frequency of CXCR4-tropism, 86% that was found in subtype A and CRF02_AG in patient samples from West Africa, demonstrates that a topical microbicide has to inhibit CXCR4-viruses frequently present in HIV-1 infected individuals. On the other hand, cervico-vaginal tissue preferentially supports the productive infection by CCR5-tropic viruses [26] . Thus, a microbicide has to block both coreceptor pathways to prevent HIV-1 sexual transmission. The HOCl-modified serum albumins, when applied as a topical microbicide, can be applied in an adequate concentration (>200 μg/ml) that is high enough to block both viruses completely.