Dynamics and origin of rebound viremia in SHIV-infected infant macaques following interruption of long-term ART.

Understanding viral rebound in pediatric HIV-1 infection may inform the development of alternatives to lifelong antiretroviral therapy (ART) to achieve viral remission. We thus investigated viral rebound after analytical treatment interruption (ATI) in 10 infant macaques orally infected with SHIV.C.CH505 and treated with long-term ART. Rebound viremia was detected within 7 to 35 days of ATI in 9 of 10 animals, with posttreatment control of viremia seen in 5 of 5 Mamu-A*01+ macaques. Single-genome sequencing revealed that initial rebound virus was similar to viral DNA present in CD4+ T cells from blood, rectum, and lymph nodes before ATI. We assessed the earliest sites of viral reactivation immediately following ATI using ImmunoPET imaging. The largest increase in signal that preceded detectable viral RNA in plasma was found in the gastrointestinal (GI) tract, a site with relatively high SHIV RNA/DNA ratios in CD4+ T cells before ATI. Thus, the GI tract may be an initial source of rebound virus, but as ATI progresses, viral reactivation in other tissues likely contributes to the composition of plasma virus. Our study provides potentially novel insight into the features of viral rebound in pediatric infection and highlights the application of a noninvasive technique to monitor areas of HIV-1 expression in children.

Fetal teratogenicity in a rhesus macaque (Macaca mulatta): Association with the chronic maternal treatment of amitriptyline.

Amitriptyline is a tricyclic antidepressant commonly prescribed in humans for pain and sleep disorders and in non-human primates for self-injurious behaviors. Here, we report a clinical case on the teratogenic effect of maternal-fetal amitriptyline exposure.

Longitudinal Anthropometric Assessment of Rhesus Macaque (Macaca mulatta) Model of Huntington Disease.

The neurodegeneration associated with Huntington disease (HD) leads to the onset of motor and cognitive impairment and their advancement with increased age in humans. In children at risk for HD, body measurement growth abnormalities include a reduction in BMI, weight, height, and head circumference. The transgenic HD NHP model was first reported in 2008, and progressive decline in cognitive behaviors and motor impairment have been reported. This study focuses on longitudinal body measurements in HD macaques from infancy through adulthood. The growth of HD macaques was assessed through head circumference, sagittal and transverse head, and crown-to-rump ('height') measurements and BMI. The animals were measured monthly from 0 to 72 mo of age and every 3 mo from 72 mo of age onward. A mixed-effect model was used to assess subject-specific effects in our nonlinear serial data. Compared with WT controls, HD macaques displayed different developmental trajectories characterized by increased BMI, head circumference, and sagittal head measurements beginning around 40 mo of age. The physiologic comparability between NHP and humans underscores the translational utility of our HD macaques to evaluate growth and developmental patterns associated with HD.

Cerebrovascular accident (stroke) in captive, group-housed, female chimpanzees.

Over a 5-y period, 3 chimpanzees at our institution experienced cerebrovascular accidents (strokes). In light of the increasing population of aged captive chimpanzees and lack of literature documenting the prevalence and effectiveness of various treatments for stroke in chimpanzees, we performed a retrospective review of the medical records and necropsy reports from our institution. A survey was sent to other facilities housing chimpanzees that participate in the Chimpanzee Species Survival Plan to inquire about their experience with diagnosing and treating stroke. This case report describes the presentation, clinical signs, and diagnosis of stroke in 3 recent cases and in historical cases at our institution. Predisposing factors, diagnosis, and treatment options of cerebral vascular accident in the captive chimpanzee population are discussed also.

Concentrations of isoflavones in macaques consuming standard laboratory monkey diet.

The soy isoflavones genistein and daidzein, as well as the daidzein metabolite equol, have structural similarities to mammalian estrogens and bind with varying affinity to both known subtypes of the estrogen receptor. Consequently, prospective studies in both humans and animals have begun to evaluate the potential effects of isoflavones on estrogen receptor-mediated phenomena. However, many diets of laboratory-housed animals derive their protein from soy and thus likely contain substantial quantities of isoflavones. Exposing experimental subjects to these isoflavones via such diets could confound studies, particularly those evaluating the effects of estrogen or estrogen-like ligands. The aim of this study was to compare the levels of circulating concentrations of isoflavones and their metabolites in monkeys fed either a soy-free diet, a soy-based diet providing 130 mg of isoflavone (daidzein, genistein, and glycitein aglycon equivalents) daily, or a commercially available 'chow' diet containing an unspecified amount of soybean meal. Animals consuming the commercial diet had serum concentrations of daidzein, genistein, and glycitein that were significantly higher than those of animals fed a soy-free diet but similar to those of monkeys fed a soybased diet formulated to be high in isoflavones. Notably, animals fed the commercial diet also had serum equol concentrations that were similar to or, in some cases, in excess of serum concentrations in the animals fed the soy diet. These data argue for the use of soy-free diets in studies investigating estrogenic effects on physiologic or behavioral endpoints.