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The effect of low pH, normally present in the female genital tract, on HIV viability was examined. HIV is more acid stable than previously reported with no substantial reduction in infectivity occurring until pH levels are reduced below 4.5. The virucidal activity of 3 topical spermicides and chlorhexidine was assessed in vitro using previously established and newly modified assay systems. None of the agents tested had a selectivity index (SI) greater than 5.2. Semen and cervical secretions were assessed for their ability to inhibit HIV-1. While no virucidal effect was found in the latter, seminal fluid was found to have significant activity against HIV-1 and a SI of approximately 50.

Nucleoside analogues previously found to be inactive against the human immunodeficiency virus (HIV) may be activated by simple chemical derivatisation. As part of our effort to deliver masked phosphates inside living cells we have discovered that certain phosphate triester derivatives of inactive nucleoside analogues become inhibitors of HIV replication. This discovery underlies the importance of the masked phosphate approach, and has significant implications for the future design of chemotherapeutic nucleoside analogues. If highly modified nucleoside analogues may be active without the intervention of nucleoside kinase enzymes, major advantage may accrue in terms of low toxicity and enhanced selectivity. Moreover, the increased structural freedom may have implications for dealing with the emergence of resistance. The concept herein described as 'kinase bypass' may thus stimulate the discovery of a new generation of antiviral agents.

Phosphate triester derivatives of AZT have been prepared as membrane-soluble pro-drugs of the bio-active nucleotides, and have been evaluated against HIV-1 in vitro. In particular, the phosphorus centre carries a trichloro- or trifluoroethyl group and a carboxyl-protected, amino-linked amino acid. The compounds are prepared using phosphorochloridate chemistry, and are characterized by a range of techniques. They display potent anti-HIV activity and low host toxicity, but surprisingly this activity does not increase on the introduction of the haloalkyl moiety. The trichloroethyl methoxyalaninyl compound is exceptional: here the activity is enhanced 50-fold by the introduction of the trichloroethyl group.

Five antigen capture enzyme-linked immunosorbent assays (ELISAs) have been assessed for detecting HIV-1 in tissue culture supernatants of cell cultures used routinely to investigate antiviral activity. Although all the ELISAs are very sensitive to low levels of antigens they have different characteristics when used for titrating virus antigens.