The authors respond to concerns about the effectiveness of HSV suppressive therapy in reducing HIV transmission. They note that their study was a proof-of-concept trial and did not predict the public health impact of HSV suppressive therapy. Data on acyclovir resistance in HIV-infected patients have not increased over the past two decades, and resistance may be declining due to widespread use of antiretroviral therapy. Acyclovir resistance does not necessarily indicate clinical failure, and genital ulceration during HSV suppressive therapy does not confirm resistance. They agree that further research is needed on acyclovir resistance, but even if confirmed, it is unlikely to outweigh the benefits of HSV suppressive therapy on HIV progression and transmission. The HIV-1 plasma viral load in the placebo group slightly increased, but the authors doubt it was due to gastrointestinal diseases. The proportion of women with gastrointestinal symptoms was higher in the placebo group, but not statistically significant. Valacyclovir and acyclovir have a safety profile similar to placebo. The hypothesis that microbial translocation causes systemic immune activation is based on commensal flora, not pathogens, and valacyclovir is unlikely to affect this mechanism. The primary outcome was genital HIV viral load, which showed little difference between groups. The authors also address coronary microvascular dysfunction due to aging, noting that age-related changes in coronary function are significant and require further study. They agree that age-related changes in coronary flow reserve are important and that further research is needed to understand the underlying mechanisms. Finally, the authors respond to a review on perioperative stroke, noting that the cited references do not support the claim that regional anesthesia is less risky than general anesthesia. The literature suggests that postoperative hypotension is more common with regional anesthesia, and further study is needed.The authors respond to concerns about the effectiveness of HSV suppressive therapy in reducing HIV transmission. They note that their study was a proof-of-concept trial and did not predict the public health impact of HSV suppressive therapy. Data on acyclovir resistance in HIV-infected patients have not increased over the past two decades, and resistance may be declining due to widespread use of antiretroviral therapy. Acyclovir resistance does not necessarily indicate clinical failure, and genital ulceration during HSV suppressive therapy does not confirm resistance. They agree that further research is needed on acyclovir resistance, but even if confirmed, it is unlikely to outweigh the benefits of HSV suppressive therapy on HIV progression and transmission. The HIV-1 plasma viral load in the placebo group slightly increased, but the authors doubt it was due to gastrointestinal diseases. The proportion of women with gastrointestinal symptoms was higher in the placebo group, but not statistically significant. Valacyclovir and acyclovir have a safety profile similar to placebo. The hypothesis that microbial translocation causes systemic immune activation is based on commensal flora, not pathogens, and valacyclovir is unlikely to affect this mechanism. The primary outcome was genital HIV viral load, which showed little difference between groups. The authors also address coronary microvascular dysfunction due to aging, noting that age-related changes in coronary function are significant and require further study. They agree that age-related changes in coronary flow reserve are important and that further research is needed to understand the underlying mechanisms. Finally, the authors respond to a review on perioperative stroke, noting that the cited references do not support the claim that regional anesthesia is less risky than general anesthesia. The literature suggests that postoperative hypotension is more common with regional anesthesia, and further study is needed.