Cyra Christina Mehta

Recent emphasis on transdisciplinary teams in science offers an opportunity for biostatisticians to assume roles beyond data management and analysis. Biostatisticians contribute to all phases of research, from hypothesis formulation and rigorous study design to data analysis and interpretation. Yet, their contributions are often underrecognized. We argue for better integration of biostatisticians in research training and team structures. Postgraduate physician-scientist training should include mentorship from biostatisticians and education on collaborative skills. Fully integrating biostatisticians as co-investigators improves rigor, reproducibility, and innovation. Institutional support, including protected time and updated promotion criteria, is essential to support sustained collaboration. Structural changes must address limited access to biostatistical resources, especially in institutions lacking Clinical and Translational Science Awards. Clarifying roles and responsibilities at the outset, including through tools like team charters, facilitates alignment and prevents conflict. Elevating biostatisticians as scientific partners strengthens team dynamics and improves research quality. Team-based biomedical research—when genuinely collaborative—synergistically advances both methodological rigor and health outcomes. This perspective is especially relevant for general internists engaged in increasingly complex, transdisciplinary research. The future of health science innovation will depend on dismantling traditional silos and promoting meaningful, equitable scientific partnerships across disciplines.

Integrase strand-transfer inhibitors (INSTIs) are associated with weight gain in people with HIV (PWH), particularly in women with HIV (WWH), but underlying mechanisms remain unclear. We used longitudinal untargeted metabolomics to identify metabolic signatures of INSTI-related weight gain in WWH. We analyzed serum from 192 participants in the Women's Interagency HIV Study: 38 virologically suppressed WWH who initiated INSTIs (INSTI group), 88 virologically suppressed WWH who remained on their original antiretroviral therapy (non-INSTI group), and 66 women without HIV (WWoH). Samples were collected at baseline (6-12 months before INSTI initiation), 1-6 months post-initiation, and 1-2 years post-initiation, with matched visits for controls. High-resolution metabolomics was performed by liquid chromatography-mass spectrometry. Within each group, linear mixed-effects models adjusted for baseline age and BMI compared longitudinal metabolite changes between weight gainers and maintainers, and significant features were analyzed by Mummichog v2.0 pathway enrichment. Mean age was 45.7 ± 8.9 years and mean BMI 32.4 ± 8.3 kg/m2, with no differences across groups; within each group, gainers and maintainers were demographically comparable (p > 0.05). In the INSTI group, metabolites differentiating gainers from maintainers were enriched in 16 pathways across timepoints, predominantly lipid-related (56%), including the polyunsaturated fatty acid (PUFA) pathways linoleic acid and arachidonic acid metabolism. In the non-INSTI and WWoH groups, differentiating metabolites spanned a broader range of pathways, including amino acid metabolism. Weight gain among INSTI-treated WWH is characterized by a distinct, lipid- and PUFA-dominated metabolic profile, providing mechanistic insight that may inform therapeutic strategies.

Background: Women with human immunodeficiency virus (HIV; WWH) and with substance use (SU) have poorer HIV-related outcomes. We characterized SU and treatment across reproductive life stages among Study of Treatment And Reproductive Outcomes (STAR) participants. Methods: The STAR is a prospective cohort of WWH and women without HIV (WWoH) across 6 Southern US sites. We analyzed baseline participant data (2021–2024) on self-reported past-year SU (nonmedical drug use, hazardous alcohol use, tobacco use, and nonmedical cannabis use), as well as drug and alcohol use treatment. We assessed SU and treatment by HIV and pregnancy status. Results: Among 891 women (526 WWH and 362 WWoH), 12% (9% of WWH and 15% WWoH; P = .02) reported past-year drug use; 15%, hazardous alcohol use (11% and 20%, respectively; P < .001); 37%, tobacco use (34% and 41%; P = .10); and 45%, cannabis use (40% and 52%; P = .001). The most frequently used drug was crack/cocaine (61%). Among pregnant women, 7% reported past-year drug use, 12% hazardous alcohol use, 28% tobacco use, and 39% cannabis use. Among women with past-year drug use (n = 102), 16% reported experiencing accidental overdose, and 23% had used any drug treatment program in the past year. There was no statistically significant difference in drug treatment by HIV or pregnancy status. Conclusions: Among reproductive-age WWH and WWoH in the Southern United States, SU was common, predominantly stimulant use with high rates of co-occurring cannabis and tobacco use. Implementation studies are needed to understand barriers and facilitators to integrating SU disorder care into HIV settings tailored to the needs of reproductive-age women.

Background: The impact of integrase strand-transfer inhibitors (INSTIs) on steatotic liver disease in women with HIV (WWH) is unknown. Methods: Using data collected in the Women's Interagency HIV Study from 2007–2020, change in Fibrosis-4 index (FIB4), aspartate aminotransferase to platelet ratio index (APRI), and nonalcoholic fatty liver disease fibrosis score (NFS) over 5 years was compared between virologically suppressed WWH who switched to or added an INSTI to their antiretroviral therapy (ART) and WWH remaining on non-INSTI ART. In participants with transient elastography (TE) measures, estimates of hepatic steatosis (controlled attenuation parameter [CAP]), fibrosis (liver stiffness [LS]), and steatohepatitis (FibroScan-aspartate aminotransferase [FAST] scores) were compared by group. Results: A total of 872 WWH (323 INSTI, 549 non-INSTI) were included, and 280 (146 INSTI, 134 non-INSTI) had TE. Of these, 61% were non-Hispanic Black; mean age was 47 years and body mass index was 31.4 kg/m2. Among non-obese women, those in the INSTI versus non-INSTI group had a greater increase in NFS (but not FIB4 or APRI) over time (study group × time, P = .015). Those in the INSTI versus non-INSTI group also had greater CAP (+25; 95% CI: .28–49; P = .048), LS (+1.23; 1.01–1.49; P = .038), and FAST scores (+1.97; 1.17–3.31; P = .011) and a 3.7 (1.2–11.4; P = .021) greater odds of having hepatic steatosis (CAP ≥248 dB/m) within 1 year of starting an INSTI. Conclusions: Hepatic steatosis risk was increased only within the first year following INSTI initiation among WWH. Longitudinal hepatic assessments are warranted to evaluate whether these changes are associated with clinically significant liver disease.

Background: Substance use (SU) contributes to poor outcomes among persons living with HIV. Women living with HIV (WWH) in the United States are disproportionately affected in the South, and examining SU patterns, treatment, and HIV outcomes in this population is integral to addressing HIV and SU disparities. Methods: WWH and comparable women without HIV (WWOH) who enrolled 2013–2015 in the Women's Interagency HIV Study Southern sites (Atlanta, Birmingham/Jackson, Chapel Hill, and Miami) and reported SU (self-reported nonmedical use of drugs) in the past year were included. SU and treatment were described annually from enrollment to the end of follow-up. HIV outcomes were compared by SU treatment engagement. Results: At enrollment, among 840 women (608 WWH, 232 WWOH), 18% (n = 155) reported SU in the past year (16% WWH, 24% WWOH); 25% (n = 38) of whom reported SU treatment. Over time, 30%, 21%, and 18% reported SU treatment at 1, 2, and 3 years, respectively, which did not significantly differ by HIV status. Retention in HIV care did not differ by SU treatment. Viral suppression was significantly higher in women who reported SU treatment only at enrollment (P = 0.03). Conclusions: We identified a substantial gap in SU treatment engagement, with only a quarter reporting treatment utilization, which persisted over time. SU treatment engagement was associated with viral suppression at enrollment but not at other time points or with retention in HIV care. These findings can identify gaps and guide future strategies for integrating HIV and SU care for WWH.

Integrase strand-transfer inhibitors (INSTIs) are associated with weight gain in women living with HIV (WLH). Relationships between drug exposure, baseline obesity, and INSTI-associated weight gain remain unclear. Data from 2006 to 2016 were analyzed from virally suppressed WLH enrolled in the Women's Interagency HIV Study, who switched/added an INSTI to antiretroviral therapy: [raltegravir (RAL), dolutegravir (DTG), or elvitegravir (EVG)]. Percent body weight change was calculated from weights obtained a median 6 months pre-INSTI and 14 months post-INSTI initiation. Hair concentrations were measured with validated liquid chromatography-mass spectrometry (MS)/MS assays. Baseline (preswitch) weight status evaluated obese (body mass index, BMI, ≥30 kg/m ² ) versus nonobese (BMI 500 cells/mm ³ , >75% with undetectable HIV-1 RNA. Over ∼1 year, women experienced median increases in body weight: 1.71% (−1.78, 5.00) with RAL; 2.40% (−2.82, 6.50) with EVG; and 2.48% (−3.60, 7.88) with DTG. Baseline obesity status modified the relationship between hair concentrations and percent weight change for DTG and RAL ( p' s < 0.05): higher DTG, yet lower RAL concentrations were associated with greater weight gain among nonobese women. Additional pharmacologic assessments are needed to understand the role of drug exposure in INSTI-associated weight gain.

Multidrug-resistant organism (MDRO) colonization is a fundamental challenge in antimicrobial resistance. Limited studies have shown that fecal microbiota transplantation (FMT) can reduce MDRO colonization, but its mechanisms are poorly understood. We conducted a randomized, controlled trial of FMT for MDRO decolonization in renal transplant recipients called PREMIX (NCT02922816). Eleven participants were enrolled and randomized 1:1 to FMT or an observation period followed by delayed FMT if stool cultures were MDRO positive at day 36. Participants who were MDRO positive after one FMT were treated with a second FMT. At last visit, eight of nine patients who completed all treatments were MDRO culture negative. FMT-treated participants had longer time to recurrent MDRO infection versus PREMIX-eligible controls who were not treated with FMT. Key taxa ( Akkermansia muciniphila , Alistipes putredinis , Phocaeicola dorei , Phascolarctobacterium faecium , Alistipes species, Mesosutterella massiliensis , Barnesiella intestinihominis , and Faecalibacterium prausnitzii ) from the single feces donor used in the study that engrafted in recipients and metabolites such as short-chain fatty acids and bile acids in FMT-responding participants uncovered leads for rational microbiome therapeutic and diagnostic development. Metagenomic analyses revealed a previously unobserved mechanism of MDRO eradication by conspecific strain competition in an FMT-treated subset. Susceptible Enterobacterales strains that replaced baseline extended-spectrum β-lactamase–producing strains were not detectable in donor microbiota manufactured as FMT doses but in one case were detectable in the recipient before FMT. These data suggest that FMT may provide a path to exploit strain competition to reduce MDRO colonization.

A substantial number of statisticians work in isolated domain science departments without access to support networks and resources typical of larger statistical units. These isolated statisticians face many challenges including limited professional networks, non‐traditional roles with idiosyncratic expectations and unique career paths. Furthermore, “the curse of success” lies ahead, as success of the department may only lead to greater demand and lagging support for the services needed. We provide suggestions for career development in an isolated environment by urging statisticians to build their network and become engaged with other statisticians to reduce isolation and identify mentors. We discuss the importance of regular communication with their supervisors to define one's role and navigate the change in expectations in the transition from a supporting role to a co‐investigator to a core leader. To help with “the curse of success,” we explain how to develop a business model with a plan for future expansion and professional development. We conclude that isolation should not be perceived as a limitation. Opportunities and resources exist within the American Statistical Association (ASA) to reduce isolation and support career development. However, there is a need for a formal career path along with evaluation criteria and example business models to support isolated statisticians striving to become core leaders.

Collaborative statisticians are instrumental to maintaining the rigor and reproducibility of multidisciplinary projects on which they collaborate. Clear, complete, well-annotated records of data, its revising, analysis, interpretation, and presentation are essential. Many students do not know how to systematically and consistently organize their digital files and cannot reliably replicate (or find!) work that may have been performed on a collaborative project. This article describes a newly developed and required one semester collaborative statistics course that includes the explicit teaching of project organization in lecture, emphasis of these skills on linked homework assignments, and their closely supervised practice through a mentored collaborative project with multidisciplinary researchers. The tripartite design provided exposure to project organization concepts during the course, encouraged straightforward implementation through homework assignments, and then challenged students with a real-world experience during a collaborative project.

Objective: Alterations in glucocorticoid receptor (GCR) function may be a risk factor for cognitive complications among older people with human immunodeficiency virus (HIV). We evaluated whether HIV serostatus and age modify the GCR function-cognition association among women. Methods: Eighty women with HIV ( n = 40, 50 years of age [older]) and 80 HIV-uninfected women ( n = 40 older, n = 40 younger) enrolled in the Women’s Interagency HIV Study completed a comprehensive neuropsychological test battery. Peripheral blood mononuclear cells collected concurrent with neuropsychological testing were assessed for GCR function. Multivariable linear regression analyses were conducted to examine whether a) HIV serostatus and age were associated with GCR function, and b) GCR function-cognition associations are moderated by HIV serostatus and age adjusting for relevant covariates. Results: Among older women, higher baseline FKBP5 expression level was associated with lower attention/working memory performance among women with HIV ( B = 6.4, standard error = 1.7, p = .0003) but not in women without HIV infection ( B = −1.7, standard error = 1.9, p = .37). There were no significant HIV serostatus by age interactions on dexamethasone (DEX)-stimulated expression of the genes regulated by the GCR or lipopolysaccharide-stimulated tumor necrosis factor α levels (with or without DEX stimulation; p values > .13). HIV serostatus was associated with GC target genes PER1 ( p = .006) and DUSP1 ( p = .02), but not TSC22D3 ( p = .32), after DEX stimulation. Conclusions: Collectively, these data suggest that HIV serostatus and age may modify the influence of the GCR, such that the receptor is likely engaged to a similar extent, but the downstream influence of the receptor is altered, potentially through epigenetic modification of target genes.