Emergence of HIV resistance is a concerning consequence of global scale-up of antiretroviral therapy (ART). To date, there is no published information about HIV resistance from the Dominican Republic. The study's aim was to determine the prevalence of transmitted drug resistance (TDR) to reverse transcriptase and protease inhibitors in a sample of chronically HIV-1-infected patients in one clinic in Santo Domingo. The data are presented in the context of a review of the TDR literature from Latin America and the Caribbean. Genotype testing was successfully performed on 103 treatment-naive adults planning to initiate antiretroviral therapy; the World Health Organization (WHO) list of surveillance drug resistance mutations (SDRM) was used to determine the presence of TDR mutations. WHO SDRM were identified in eight patients (7.8%); none had received sdNVP. There were no significant differences in epidemiologic or clinical variables between those with or without WHO SDRM. The prevalence of WHO SDRM was 1.0% and 6.8% for nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors, respectively. No WHO SDRMs for protease inhibitors were identified. Among 12 studies of TDR in the region with a sample size of at least 100 subjects, the reported prevalence of SDRM ranged from 2.8% to 8.1%. The most commonly identified SDRM was K103N. This information adds to our understanding of the epidemiology of TDR in the region and the possible role such mutations could play in undermining first-line treatment. Ongoing surveillance is clearly needed to better understand the TDR phenomenon in the Caribbean.

Undergraduate students participating in the UCLA Undergraduate Research Consortium for Functional Genomics (URCFG) have conducted a two-phased screen using RNA interference (RNAi) in combination with fluorescent reporter proteins to identify genes important for hematopoiesis in Drosophila. This screen disrupted the function of approximately 3500 genes and identified 137 candidate genes for which loss of function leads to observable changes in the hematopoietic development. Targeting RNAi to maturing, progenitor, and regulatory cell types identified key subsets that either limit or promote blood cell maturation. Bioinformatic analysis reveals gene enrichment in several previously uncharacterized areas, including RNA processing and export and vesicular trafficking. Lastly, the participation of students in this course-based undergraduate research experience (CURE) correlated with increased learning gains across several areas, as well as increased STEM retention, indicating that authentic, student-driven research in the form of a CURE represents an impactful and enriching pedagogical approach.

BackgroundCardiovascular disease (CVD) is a leading health threat for HIV+ patients on antiretroviral therapy (ART); cardiometabolic comorbidities are key predictors of risk. Data are limited on incidence of metabolic comorbidities in HIV+ individuals initiating ART in low and middle income countries (LMICs), particularly for Hispanics. We examined incidence of diabetes and obesity in a prospective cohort of those initiating ART in the Dominican Republic.MethodsParticipants ≥18 years, initiating ART <90 days prior to study enrollment, were examined for incidence of impaired fasting glucose (IFG), diabetes mellitus (DM), overweight, and obesity. Fasting plasma glucose (FPG) 100-125mg/dl defined IFG; FPG ≥126 mg/dl, diagnosis per medical record, or use of hypoglycemic medication defined DM. Overweight and obesity were BMI 25–30 and ≥30kg/m2, respectively. Dyslipidemia was total cholesterol ≥240mg/dl or use of lipid-lowering medication. Framingham risk equation was used to determine ten-year CVD risk at the end of observation.ResultsOf 153 initiating ART, 8 (6%) had DM and 23 (16%) had IFG at baseline, 6 developed DM (28/1000 person-years follow up [PYFU]) and 46 developed IFG (329/1000 PYFU). At baseline, 24 (18%) were obese and 36 (27%) were overweight, 15 became obese (69/1000 PYFU) and 22 became overweight (163/1000 PYFU). Median observation periods for the diabetes and obesity analyses were 23.5 months and 24.3 months, respectively. Increased CVD risk (≥10% 10-year Framingham risk score) was present for 13% of the cohort; 79% of the cohort had ≥1 cardiometabolic comorbidity, 48% had ≥2, and 13% had all three.ConclusionsIn this Hispanic cohort in an LMIC, incidences of IFG/DM and overweight/obesity were similar to or higher than that found in high income countries, and cardiometabolic disorders affected three-quarters of those initiating ART. Care models incorporating cardiovascular risk reduction into HIV treatment programs are needed to prevent CVD-associated mortality in this vulnerable population.

Primary membranous nephropathy (MN) is an autoimmune disease caused by autoantibody binding to podocytes in human glomeruli. The disease leads to end-stage renal disease in about 30% of patients, even after treatment with immunosuppressive therapies. The discovery of serum autoantibodies against the Phospholipase A 2 Receptor 1 (PLA 2 R1) in 70% of patients with MN has resulted in substantial improvements of diagnosis, disease classification, treatment and prognosis. However, due do the lack of a rodent animal model, it has not been formally proven that human PLA 2 R1-antibodies induce disease. With the aim to define the role of human PLA 2 R1-antibodies in MN pathogenesis, we studied the impact of human PLA 2 R1-antibodies in minipigs. Methods: For passive transfer experiments, minipigs received plasma or purified total IgG from patients with PLA 2 R1-associated MN or from healthy controls. Further, active immunization was performed using human recombinant PLA 2 R1 protein. The presence of PLA 2 R1antibodies and development of proteinuria were monitored in the serum and urine of minipigs. Kidney samples were analyzed using immunohistochemistry, immunofluorescence and electron microscopy. Results: PLA 2 R1 is expressed on the podocytes on the minipig in a pattern identical to that in human kidneys. Human PLA 2 R1-antibodies bind to the minipig PLA 2 R1 both in vitro and in vivo. The passive transfer experiments using plasma or purified IgG from patients with PLA 2 R1-associated MN to minipigs resulted in development of all functional and morphologic characteristics of human MN in minipigs. Human PLA 2 R1-antibodies were detectable in the blood of the minipigs and could be eluted from the glomeruli of the minipigs. Importantly, the eluted human PLA 2 R1-antibodies were of the IgG4 subclass. Transfer of healthy human plasma of total IgG did not lead to any histomorphological changes resembling MN. The active immunization of minipigs with the human PLA 2 R1 protein led to generation of anti-PLA 2 R1 antibodies, which also resulted in the induction of all characteristics of human MN in the kidneys of the minipigs. Conclusions: By applying a translational approach from humans to minipigs we demonstrated that human PLA 2 R1-antibodies are pathogenetic and induce MN. In addition, we created a humanized model of autoimmune PLA 2 R1-induced MN by active immunization of minipigs with PLA 2 R1.