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Oral preexposure prophylaxis for HIV--another arrow in the quiver?

New England Journal of Medicine (Impact Factor: 54.42). 12/2010; 363(27):2663-5. DOI: 10.1056/NEJMe1012929
Source: PubMed
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    ABSTRACT: BACKGROUND: Developing an objective, reliable method to determine semen exposure in cervicovaginal fluids is important for accurately studying the efficacy of vaginal microbicides and contraceptives. Y-chromosome biomarkers offer better stability, sensitivity, and specificity than protein biomarkers. TSPY4 belongs to the TSPY (testis-specific protein Y-encoded) family of homologous genes on the Y-chromosome. Using a multiplex PCR amplifying TSPY4, amelogenin, and Sex-determining region in the Y chromosome (SRY), our objective was to determine whether a gene in the TSPY family was a more sensitive marker of semen exposure in cervicovaginal fluids than SRY. STUDY DESIGN: The multiplex polymerase chain reaction (PCR) was developed using sperm and vaginal epithelial (female) DNA. Diluted sperm DNA and mixed male/female DNA was used to determine the sensitivity of the multiplex PCR. Potential interference of TSPY4 amplification by components in cervicovaginal and seminal fluids was determined. TSPY4 and SRY amplification was also investigated in women participating in a separate IRB-approved clinical study in which cervicovaginal swab DNA was collected before semen exposure and at various time points after exposure. RESULTS: TSPY4, SRY, and amelogenin were amplified in sperm DNA, but only amelogenin in female DNA. The limit of sperm DNA from which TSPY4 could be amplified was lower than SRY (4 pg vs 80 pg). TSPY4 could also be amplified from mixed male/female DNA. Amplification was not affected by cervicovaginal and seminal components. Using cervicovaginal swab DNA from three women before and after semen exposure, TSPY4 was detected up to 72 h post exposure while SRY detection was observed up to 24-48 h. TSPY4 was detected up to 7 days post exposure in one out of three women. CONCLUSIONS: We have demonstrated that TSPY4 is a new sensitive, and sperm-specific biomarker. The multiplex PCR incorporating this new biomarker has potential to be an objective measure for determining semen exposure in clinical trials of vaginal products such as contraceptives and HIV pre/post-exposure prophylaxis agents.
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    ABSTRACT: The RV144 trial on the ALVAC/AIDSVAX candidate HIV vaccine, carried out in Thailand, showed short-lived protection against infection. Using a deterministic compartmental model we explored the potential impact of this vaccine on heterosexual HIV transmission in Thailand. Both one-off vaccination strategies, as well as strategies with regular boosting, either annually or every two years, were explored. Both targeting the general adult population and prioritizing sex workers were modeled. The impact of risk compensation among high risk groups, as well as whether higher levels of safe sex in high risk groups could be an alternative to vaccination, was studied. One-off vaccination campaigns had only transient effects, and boosting appears to be a key component of successful vaccination campaigns. Intensive vaccination campaigns may reduce HIV incidence by up to 75% after 10 years of vaccination. Targeting only sex workers has a smaller impact but has a more favorable cost-benefit ratio. Risk compensation has the potential of undoing much of the benefits of a vaccination program and may even increase incidence. In contrast, higher levels of safe sex among sex workers would provide a viable alternative to vaccinating this group. The new vaccine holds promise for controlling HIV in Thailand and similar countries. In view of the short lived protection of the vaccine, regular boosting of immunity as well as avoidance of risk compensation are essential. Targeting sex workers would achieve the greatest reduction in incidence per vaccination and may be considered for expensive vaccines but its cost-effectiveness has to be compared to alternatives.
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