Screening and Enrollment by Sex in Human Immunodeficiency Virus Clinical Trials in the United States.

BACKGROUND: Women are underrepresented in human immunodeficiency virus (HIV) research in the United States. To determine if women screening for HIV clinical trials enrolled at lower rates than men, we performed a retrospective, cross-trial analysis. METHODS: We conducted an analysis of screening and enrollment during 2003-2013 to 31 clinical trials at 99 AIDS Clinical Trials Group network research sites in the United States. Random-effects meta regression estimated whether sex differences in not enrolling ("screen out") varied by various individual, trial, or site characteristics. RESULTS: Of 10 744 persons screened, 18.9% were women. The percentages of women and men who screened out were 27.9% and 26.5%, respectively (P = .19); this small difference did not significantly vary by race, ethnicity, or age group. Most common reasons for screening out were not meeting eligibility criteria (30-35%) and opting out (23%), and these did not differ by sex. Trial and research site characteristics associated with variable screen-out by sex included HIV research domain and type of hemoglobin eligibility criterion, but individual associations did not persist after adjustment for multiple testing. CONCLUSIONS: In the absence of evidence of significantly higher trial screen-out for women, approaching more women to screen may increase female representation in HIV trials.

Perspectives on Polycystic Ovary Syndrome: Is Polycystic Ovary Syndrome Research Underfunded?

Context: Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic abnormality with a worldwide prevalence of 4% to 21%, depending on diagnostic criteria. The National Institutes of Health (NIH) is the largest single funding agency in the world; it invests nearly $30.0 billion annually in biomedical research. Evidence Acquisition: Using the NIH Research Portfolio Online Reporting tool, we searched for all grants awarded by the NIH for PCOS and three other disorders with similar degrees of morbidity and similar or lower mortality and prevalence [rheumatoid arthritis (RA), tuberculosis (TB), and systemic lupus erythematosus (SLE)]. Evidence Synthesis: We compared funding by the NIH for PCOS, RA, TB, and SLE research for the years 2006 to 2015, inclusive. Conclusion: PCOS, compared with RA, TB, and SLE, was relatively less funded (total mean 10-year funding was $215.12 million vs $454.39 million, $773.77 million, and $609.52 million, respectively). Funding for PCOS was largely provided by one NIH Institute/Center (ICs) vs at least two ICs for SLE and RA; more individual Research Project Grants were awarded for RA, SLE, and TB than for PCOS, whereas PCOS funding was more likely to be through General Clinical Research Centers Program or Specialized Centers Program awards. Our data suggest that PCOS research may be underfunded considering its prevalence, economic burden, metabolic morbidity, and negative impact on quality of life. Greater education of NIH leaders, including those at the National Heart, Lung, and Blood Institute and National Institutes of Diabetes and Digestive and Kidney Diseases; other federal and state agency leads; elected leaders; and the general public by professional societies, the scientific community, and patient advocates regarding this disorder is needed.

Genetics of polycystic ovary syndrome.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a hormonal and metabolic disorder affecting 5 to 20% of reproductive-aged women worldwide that results in androgen excess, menstrual dysfunction and oligo-ovulatory subfertility, with increased risks for type 2 diabetes, endometrial adenocarcinoma, and potentially vascular disease, among other morbidities. PCOS is a complex genetic trait with strong heritability accounting for as high as 70% of the development of the disorder. Areas covered: The authors summarize the historical and recent findings of genetic studies of PCOS, such as familial studies, twin studies, and molecular genetic studies, including the results of recent genome wide associated studies. PubMed, Medline and Embase database were used to search relevant articles. Included studies were predominately conducted in Asia, North Africa, North America, and Europe. Expert commentary: Current studies aim to establish the role and function of identified genes; such efforts could serve as potential platforms for novel diagnostic and treatments for PCOS patients. The etiology of PCOS will be better understood as more data is gathered systematically, subjects are better phenotyped larger populations are recruited, and a better understanding of the role of genetic architecture, genetic variation, epigenetics, and gene-gene, gene-environment, and gene-phenotype interaction is obtained.

Phenotypes and body mass in women with polycystic ovary syndrome identified in referral versus unselected populations: systematic review and meta-analysis.

OBJECTIVE: To compare the prevalence of polycystic ovary syndrome (PCOS) phenotypes and obesity among patients detected in referral versus unselected populations. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Thirteen thousand seven hundred ninety-six reproductive-age patients with PCOS, as defined by the extended Rotterdam 2003 criteria. INTERVENTION(S): Review of PUBMED, EMBASE, and Cochrane Library, 2003-2016. Only observational studies were included. Data were extracted using a web-based, piloted form and combined for meta-analysis. MAIN OUTCOME MEASURE(S): PCOS phenotypes were classified as follows: phenotype A, clinical and/or biochemical hyperandrogenism (HA) + oligo-/anovulation (OA) + polycystic ovarian morphology (PCOM); phenotype B, HA+OA; phenotype C, HA+PCOM; and phenotype D, OA+PCOM. RESULT(S): Forty-one eligible studies, reporting on 43 populations, were identified. Pooled estimates of detected PCOS phenotype prevalence were consequently documented in referral versus unselected populations, as [1] phenotype A, 50% (95% confidence interval [CI], 46%-54%) versus 19% (95% CI, 13%-27%); [2] phenotype B, 13% (95% CI, 11%-17%) versus 25% (95% CI, 15%-37%); [3] phenotype C, 14% (95% CI, 12%-16%) versus 34% (95% CI, 25-46%); and [4] phenotype D, 17% (95% CI, 13%-22%) versus 19% (95% CI, 14%-25%). Differences between referral and unselected populations were statistically significant for phenotypes A, B, and C. Referral PCOS subjects had a greater mean body mass index (BMI) than local controls, a difference that was not apparent in unselected PCOS. CONCLUSION(S): The prevalence of more complete phenotypes in PCOS and mean BMI were higher in subjects identified in referral versus unselected populations, suggesting the presence of significant referral bias.

Lack of resistance to integrase inhibitors among antiretroviral-naive subjects with primary HIV-1 infection, 2007-2013.

BACKGROUND: US guidelines recommend genotyping for persons newly diagnosed with HIV infection to identify transmitted drug resistance mutations associated with decreased susceptibility to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors. To date, testing for integrase strand transfer inhibitor (INSTI) mutations has not been routinely recommended. We aimed to evaluate the prevalence of transmitted INSTI mutations among persons with primary HIV-1 infection in Seattle, WA, USA. METHODS: Persons with primary HIV-1 infection have enrolled in an observational cohort at the University of Washington Primary Infection Clinic since 1992. We performed a retrospective analysis of plasma specimens collected prospectively from the 82 antiretroviral-naive subjects who were enrolled from 2007-2013, after FDA-approval of the first INSTI. Resistance testing was performed by consensus sequencing. RESULTS: Specimens for analysis had been obtained a median of 24 (IQR 18-41, range 8-108) days after the estimated date of HIV-1 infection. All subjects were infected with HIV-1 subtype B except for one subject infected with subtype C. Consensus sequencing identified no subjects with major INSTI mutations (T66I, E92Q, G140S, Y143C/H/R, S147G, Q148H/K/R, N155H). Using exact binomial CIs, the upper bound of the 95% CI was 4.4%. CONCLUSIONS: Although our sample size was small, this study does not support the need at this time to evaluate integrase mutations as part of routine consensus sequencing among persons newly diagnosed with HIV-1 infection. However, it is likely that the prevalence of transmitted INSTI mutations may increase with the recent commercial introduction of additional INSTIs and presumably greater INSTI use among persons living with HIV-1.