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Background: Pig‐tailed macaques (PTMs) are commonly used as preclinical models to assess antiretroviral drugs for HIV prevention research. Drug toxicities and disease pathologies are often preceded by changes in blood hematology. To better assess the safety profile of pharmaceuticals, we defined normal ranges of hematological values in PTMs using an Isolation Forest (iForest) algorithm. Methods: Eighteen female PTMs were evaluated. Blood was collected 1–24 times per animal for a total of 159 samples. Complete blood counts were performed, and iForest was used to analyze the hematology data to detect outliers. Results: Median, IQR, and ranges were calculated for 13 hematology parameters. From all samples, 22 outliers were detected. These outliers were excluded from the reference index. Conclusions: Using iForest, we defined a normal range for hematology parameters in female PTMs. This reference index can be a valuable tool for future studies evaluating drug toxicities in PTMs. [ABSTRACT FROM AUTHOR]

Background An established macaque model to assess HIV interventions against penile transmission is currently not available. Physiological changes during penile erections may affect susceptibility to infection and drug pharmacokinetics ( PK). Here, we identify methods to establish erections in macaques to evaluate penile transmission, PK, and efficacy under physiologic conditions. Methods Penile rigidity and length were evaluated in eight rhesus macaques following rectal electrostimulation ( RES), vibratory stimulation ( VS), or pharmacological treatment with Sildenafil Citrate (Viagra) or Alprostadil. Results Rectal electrostimulation treatment increased penile rigidity (>82%) and length (2.5 ± 0.58 cm), albeit the response was transient. In contrast, VS alone or coupled with Viagra or Alprostadil failed to elicit an erection response. Conclusion Rectal electrostimulation treatment elicits transient but consistent penile erections in macaques. High rigidity following RES treatment demonstrates increased blood flow and may provide a functional model for penile PK evaluations and possibly simian immunodeficiency virus ( SIV) transmission under erect conditions. [ABSTRACT FROM AUTHOR]

Background Hormonal changes during menstrual cycling may affect susceptibility to HIV. Methods We determined the simian human immunodeficiency virus ( SHIV) acquisition time point in 43 cycling pigtail macaques infected by repeated vaginal virus exposures initiated randomly in the cycle. Results SHIV infection was first detected in the follicular phase in 38 macaques (88%), and in the luteal phase in five macaques (12%), indicating a statistically significant timing difference. Assuming a 7-day eclipse phase, most infections occurred during or following a high-progesterone period associated with menstruation, vaginal epithelium thinning, and suppressed mucosal immunity. Conclusions This raises questions whether other high-progesterone conditions (pregnancy, hormonal contraception) similarly affect HIV risk. [ABSTRACT FROM AUTHOR]

Background and Methods Cell isolation from macaque tissues involves laborious enzymatic digestion. The Medimachine provides a simpler, quicker non-enzymatic method, yielding 1.5-5 million cells/g of vaginal or rectal tissue from pigtailed macaques. Results and Conclusions Flow cytometry analysis of the two methods revealed similar levels of cell viability and most major cell lineage and activation markers. [ABSTRACT FROM AUTHOR]