The Activity of Candidate Virucidal Agents, Low pH and Genital Secretions against HIV-1 In Vitro

Abstract

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.

Comparison of Human Immunodeficiency Virus Type 1-Specific Inhibitory Activities in Saliva and Other Human Mucosal Fluids

“…The intersubject variation in anti-HIV-1 activity shown with all mucosal fluid types in this study is consistent with intersubject variation observed in previous studies with saliva (6,10,24,54) and seminal fluid (32). However, the finding that intersubject variation also occurs in fluids other than saliva and seminal fluid has not previously been demonstrated.…”

“…Poly-L-lysine hydrobromide (50 l of 50 g/ml; Sigma) was used to coat 96-well microtiter plates at room temperature for 1 h. HIV-1 RF (50 TCID 50 s in 25 l of growth medium) was added to each well and incubated for 1 h at room temperature to allow HIV-1 binding. Each mucosal fluid sample (50 l) was added in duplicate and incubated at 37°C in 5% CO 2 for 1 h. All seminal fluid samples were assessed for anti-HIV-1 activity at a dilution of 1:50 with growth medium to avoid cytotoxicity (32). C8166 cells were then added at a concentration of 4 ϫ 10 4 cells in 300 l growth medium and incubated at 37°C in 5% CO 2 for 72 h. Plates were washed three times with PBS between all stages.…”

“…The 3-day microtiter-based infection assay described by O'Connor et al (32) was adapted as follows. Poly-L-lysine hydrobromide (50 l of 50 g/ml; Sigma) was used to coat 96-well microtiter plates at room temperature for 1 h. HIV-1 RF (50 TCID 50 s in 25 l of growth medium) was added to each well and incubated for 1 h at room temperature to allow HIV-1 binding.…”

“…Endogenous anti-HIV-1 activity has been demonstrated in whole, parotid, and submandibular/sublingual (sm/sl) saliva, colostrum, whole milk, and seminal plasma (1,11,13,24,29,32,38,45,46,51) but not in cerebrospinal fluid or urine (38). The incidence of oral HIV-1 transmission is very low and can be attributed both to endogenous salivary factors that prevent oral excretion of transmissible levels of virus (45,47,48) and to lysis of HIV-infected cells due to the hypotonicity of saliva (2,3).…”

Role of Semen in Modulating the Female Genital Tract Microenvironment – Implications for HIV Transmission

“…Seminal fluid and whole semen have demonstrated anti-HIV activity in vitro in T-lymphocyte cell lines. 54 Cationic polypeptides contained in seminal plasma 55 and reactive oxygen species produced by seminal leukocytes and spermatozoa 56 provide intrinsic antiviral activity against HIV-1. Seminal plasma also blocks the attachment of HIV-1 to DC-SIGN, thus preventing viral transfer to CD4 + target cells in vitro.…”