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Age-associated comorbidities are higher in people with HIV (PWH) than HIV-negative individuals. This is partially attributed to immune activation and CD38 expression on T cells driving chronic inflammation. However, the exact contribution of CD38-expressing T cells on the proinflammatory response is not completely understood.CD38-expressing CD8 + T lymphocytes were measured from PWH and HIV-negative individuals. Mitochondrial mass, superoxide content, membrane depolarization of CD4 + and CD8 + T lymphocytes, and cytokine production after HIV(Gag)-specific peptide stimulation from CD38 + CD8 + T lymphocytes of PWH were measured to link biological effects of CD38 expression on cellular metabolism.The frequency of activated CD8 + CD38 + T cells persists in PWH on ART compared with HIV-negative individuals. Higher CD38 expression is associated with mitochondrial biogenesis and HIV(Gag)-specific proinflammatory cytokine production in PWH. Blockade of CD38 results in lower Gag-specific cytokine production.ART only partially reduced HIV-induced CD38 expression on CD8 + T cells. CD8 + CD38 + T cells are highly activated in vivo, and HIV-specific stimulation in vitro augments CD38 expression, contributing to a proinflammatory response despite virologic control with ART. Therefore, CD38 is a potential therapeutic target for mitigating chronic inflammation that likely drives cellular aging, comorbidities, and end-organ disease in PWH.

Background Antiretroviral treatment (ART) has increased the life expectancy of people with HIV (PWH), however, comorbidities are higher in PWH than HIV-negative individuals. This is partly due to accelerated cellular aging, a consequence of CD38 expression, mitochondrial dysfunction, and inflammation. However, the role of CD38-expressing T cells on accelerated cellular aging in PWH is not completely understood. Methods The proportion of cytotoxic CD38+ CD8+ T lymphocytes from peripheral blood mononuclear cells (PBMCs) of PWH and HIV negative-individuals was measured. PBMCs from PWH on ART were cultured with or without gag-specific peptide stimulation and cytokine production was detected by flow cytometry. Mitochondrial function from T cells of PWH on ART and healthy donors was compared. Last, we generated a humanized (NSG) mouse model and infected mice with HIV (Bal strain) to determine the proportion of CD38+ T cells and cytokine production. Results Mean CD38 expression on CD8+ T cells was significantly different between PWH on ART and HIV-negative individuals (Figure 1). In PWH, gag-specific peptide stimulation of CD8+ T cells significantly increased CD38 expression (Figure 2A) and augmented secretion of IFNγ+ and TNFα+ (Figure 2B). There was a higher expression of CD38 among CD8+ T cells that produced IFNγ and TNFα (Figures 2C). T cells in PWH have altered mitochondrial function (Figures 2D-2F). Finally, HIV-infected NSG mice had T cell changes consistent with HIV infection (Figure 3A), a higher proportion of CD38+ T cells with an activated phenotype (Figures 3B and 3C), and significantly higher levels of inflammatory cytokines (Figure 3D). Figure 1.CD38 expression in PWH and HIV-negative individuals.Mean %CD38+CD8+ T cells in people with HIV (PWH) on and off antiretroviral therapy (ART) and HIV-negative individuals. Statistical significance was tested by Kruskal-Wallis test with post hoc analysis (Dunn’s Multiple comparison test). ****, P value< 0.0001.Figure 2.Cytokine production in response to gag stimulation from CD38+CD8+ T cells and mitochondrial function in T cells of PWH. Figure 2. (A) Frequency of CD38+ cells in gag-peptide stimulated CD8+ T cells and unstimulated cells. (B) Frequency of IFNγ and TNFα producing CD8+ T cells in gag-stimulated and unstimulated cells. Proportion of CD38+ cells among (C) IFNγ-/IFNγ+ and TNFα-/TNFα+ gag-peptide stimulated CD8+ T cells. Statistical significance was tested by paired t test. (D) Mitochondrial mass was determined by measuring the mean fluorescence intensity (MFI) of mitochondria-specific dye mitotracker green (MTG) among CD8+ T lymphocytes. (D) Frequency of mitochondrial superoxide positive lymphocytes and level of mitochondrial superoxide (MFI) were determined by staining the CD8+ T lymphocytes with mitosox red dye. (F) Mitochondrial membrane depolarization was determined by the red to green ratio of MFIs of mitochondrial membrane potential-dependent dye JC-1 among the CD8+ T lymphocytes. Statistical significance was tested by Mann-Whitney test. *, P value< 0.05; **, P value< 0.01; ***, P value< 0.001; ns – not significant. PWH=People with HIV. HD= Healthy Donors. Figure 3.Lymphocyte changes, CD38 expression, and cytokine production in HIV-infected NSG mice.(A) Frequency of CD4+ and CD8+ T lymphocytes and comparison of ratio of the frequencies of CD4+ to CD8+ T cells between control and HIV infected humanized mice. Statistical significance determined by Mann-Whitney test. (B) Frequency of CD38+ and CD38+HLADR CD4+ (A) and CD8+ (B) T cells in HIV- infected humanized mice compared to control. Statistical significance determined by Mann-Whitney test. (D)Cytokine measurements of HIV-infected humanized mice and controls. Statistical significance was tested by independent t test. *, P value< 0.05; **, P value< 0.01; ns – not significant. HLADR= Human Leukocyte Antigen – DR isotype, IFN=Interferon, IP=Inducible Protein, MCP=Monocyte Chemoattractant Protein, TNF=Tumor Necrosis Factor, IL=Interleukin. Conclusion ART decreases CD38 expression on CD8+ T cells, but not to the levels of HIV-negative individuals. In vitro, T cells of PWH have altered mitochondrial function, and HIV-specific stimulation augments CD38 expression on CD8+ T cells and contributes to a proinflammatory response. These findings translate to a humanized mouse model, where HIV infection upregulates CD38 expression and cytokine production. Together, these data suggest that CD38 is a potential therapeutic target for mitigating the mitochondrial dysfunction and chronic inflammation that drive cellular aging and comorbidities in PWH. Disclosures Poonam Mathur, DO, MPH, American Academy of HIV Medicine: Honoraria|Med Learning Group: Speaker/presenter|NACCME: Advisor/Consultant|NKGP Pharma: Advisor/Consultant Shyam Kottilil, MD, PhD, Arbutus Pharmaceuticals: Grant/Research Support|Gilead: Grant/Research Support|Merck: Grant/Research Support|Regeneron Pharmaceuticals: Advisor/Consultant|Silverback Therapeutics: Advisor/Consultant|The Liver Company: Advisor/Consultant|Yufan Biotechnologies: Advisor/Consultant.

Chronic infection with hepatitis B and C viruses (HBVHCV) is a major contributor to liver disease and liver-related mortality in Uzbekistan. There is a need to demonstrate the feasibility of large-scale simplified testing and treatment to implement a national viral hepatitis elimination program.13 polyclinics were utilized to screen, conduct follow up biochemical measures, and treat chronic HBV and HCV infection in the general adult population. Task shifting and motivational interviewing training allowed nurses to provide rapid screening and general practitioners (GPs) to treat individuals on-site. An electronic medical system tracked individuals through the cascade of care.The use of rapid tests allowed for screening of 60,769 people for HCV and HBV over 6 months and permitted outdoor testing during the COVID-19 pandemic along with COVID testing. 13-14% of individuals were lost to follow-up after the rapid test, and another 62-66% failed to come in for their consultation. One stop testing and treatment did not result in a statistically increase in retention and lack of patient awareness of viral hepatitis was identified as a key factor. Despite training, there were large differences between GPs and patients initiating treatment.The current study demonstrated the feasibility of large-scale general population screening and task shifting in low- and middle-income countries. However, such programs need to be proceeded by awareness campaign to minimize loss to follow up. In addition, multiple trainings are needed for GPs to bolster their skills to talk to patients about treatment.

Summary Background Treatment for infection with hepatitis C virus (HCV) during pregnancy has not yet been approved; however, interventions specifically targeting women, especially those of childbearing age (15–49 years), could prevent vertical transmission and community spread. To assess the impact of such interventions, improved prevalence estimates in this group are needed. We aimed to estimate the global prevalence of viraemic HCV in 2019 among women of childbearing age. Methods In this modelling study, we used previously developed models for 110 countries inputted with country-specific demographic and HCV epidemiology data. We did a literature review, searching PubMed, Embase, and grey literature for studies published between Jan 1, 2000, and June 30, 2018, reporting HCV antibody or viraemic prevalence in women of childbearing age. Studies from the literature review and studies in models were compared by use of a data quality scoring system and models were updated, as appropriate, when a better study was identified. We used these HCV disease burden models to calculate the 2019 prevalence of viraemic HCV in women of childbearing age. In countries without a model, prevalence was extrapolated by Global Burden of Disease (GBD) region. Findings An estimated 14 860 000 (95% uncertainty interval [UI] 9 667 000–18 282 000) women aged 15–49 years had HCV infection worldwide in 2019, corresponding to a viraemic prevalence of 0·78% (95% UI 0·62–0·86). Globally, HCV prevalence increased with age, rising from 0·25% (95% UI 0·20–0·27) in women aged 15–19 years to 1·21% (0·97–1·34) in women aged 45–49 years. China (16% of total infections) and Pakistan (15%) had the greatest numbers of viraemic infections, but viraemic prevalence was highest in Mongolia (5·14%, 95% CI 3·46–6·28) and Burundi (4·91%, 3·80–18·75). Of the countries with 500 cases or more, viraemic prevalence was lowest in Chile (0·07%, 95% UI 0·04–0·12). Among the GBD regions, eastern Europe had the highest viraemic prevalence (3·39%, 95% UI 1·88–3·54). By WHO region, the Eastern Mediterranean region had the highest viraemic prevalence (1·75%, 95% UI 1·26– 1·90). Interpretation Most research on HCV disease burden among women aged 15–49 years focuses on pregnant women. Using modelling, this analysis provides global and national estimates of HCV prevalence in all women of childbearing age. These data can inform preconception test-and-treat strategies to reduce vertical transmission and total disease burden. Funding Gilead Sciences, John C Martin Foundation, private donors.

OBJECTIVE The ANCHOR program offered buprenorphine treatment to people who inject drugs engaged in hepatitis C (HCV) treatment at a Washington, DC harm reduction organization. This analysis describes the program model and outcomes of the opioid care continuum at 1 year. METHODS Primary outcomes were initiation of buprenorphine and retention in care, defined by an active buprenorphine prescription at given time points. Secondary outcomes included treatment interruptions, reasons for treatment noninitiation and termination, buprenorphine and opiate use, and HIV risk behaviors. Buprenorphine and opiate use were measured by urine toxicology screens and HIV risk behavior was quantified using a validated survey. RESULTS Of 67 patients receiving HCV treatment not on opioid agonist therapy at baseline, 96% (n = 64) were interested and 73% (n = 49) initiated buprenorphine. Retention was 82% (n = 40), 65% (n = 32), and 59% (n = 29) at months 1, 6, and 12, respectively. Retention at 12 months was associated with self-reported engagement in routine medical care (P

Here, we present a case of an immunocompetent 37-year old male who developed Aspergillus fumigatus osteomyelitis 16 years after extensive chest wall reconstructive surgery for Ewing sarcoma. His treatment course was complicated by a severe adverse drug reaction to voriconazole, requiring the use of oral posaconazole therapy. Serum 1,3-beta-D glucan assay was utilized to dictate the duration of posaconazole therapy. The patient successfully completed 9 months of oral posaconazole therapy and has not had clinical recurrence for 9 months off antifungal therapy.

ANS-6637, a pro-drug of GS-548351, is a selective, reversible inhibitor of aldehyde dehydrogenase isoform 2 under development as an anticraving agent for the treatment of substance use disorders. In vitro testing indicates that GS-548351 is an inhibitor and inducer of cytochrome P450 family 3, subfamily A (CYP3A). In this phase 1 single-center, open-label, fixed-sequence drug-drug interaction study we assessed the impact of steady-state GS-548351 on single-dose pharmacokinetics of midazolam, an index substrate for CYP3A. Twelve healthy volunteers received 600 mg of ANS-6637 by mouth daily from study days 3 to 8 and a single 5-mg oral dose of midazolam on days 1 and 8. Pharmacokinetic samples were collected over 24 hours on days 1 and 8, then analyzed using liquid chromatography-tandem mass spectrometry. The prespecified no-effect range for the 90% confidence interval (CI) of the geometric mean ratio (GMR) of midazolam coadministered with ANS-6637 (day 8) compared with midazolam alone (day 1) was 0.7-1.43. There was an increase in midazolam AUC0-∞ (GMR [90%CI]) that was within the no-effect range (1.26 [1.12-1.425]) and an increase in midazolam Cmax that was outside the range (1.22 [1.03-1.45]). The AUC0-∞ (1.08 [0.91-1.27]) and Cmax (0.95 [0.75-1.2]) of 1-hydroxymidazolam, the primary metabolite of midazolam, were also within the no-effect range. A single grade 3 adverse event (alanine aminotransferase elevation) was identified and resolved following discontinuation of the study drug. Overall, multidose ANS-6637 was well tolerated and did not alter the PK of midazolam beyond a small increase in AUC0-∞ that is unlikely to be clinically significant.

Background People who inject drugs have a high prevalence of hepatitis C virus (HCV) and significant disease associated with drug use; however, HCV treatment often occurs in absence of interventions to address opioid use disorder and drug use–related harms. The impact of concurrent initiation of opioid agonist therapy (OAT) on HCV treatment and drug use outcomes is unknown. Methods In this prospective, open-label, observational trial at a harm reduction organization’s drop-in center in Washington, DC, 100 patients with chronic HCV infection, opioid use disorder, and ongoing injection drug use were treated with sofosbuvir-velpatasvir for 12-weeks and offered buprenorphine initiation. The primary end point was sustained virologic response (SVR), and secondary end points included uptake of and retention in OAT, change in risk behavior, and determinants of SVR. Results Eighty-two patients (82%) achieved SVR, which was not associated with baseline OAT status (P = .33), on-treatment drug use (P >.99), or imperfect daily adherence (P = .35) but was significantly associated with completing 2 or more 28-pill bottles of sofosbuvir-velpatasvir (P Conclusions The Novel Model of Hepatitis C Treatment as an Anchor to Prevent HIV, Initiate Opioid Agonist Therapy, and Reduce Risky Behavior study demonstrates high uptake of buprenorphine collocated with HCV treatment, and it shows that concurrent initiation of OAT with HCV treatment can result in high rates of SVR while reducing risks associated with drug use. Clinical Trials Registration NCT03221309.

Background Daily oral preexposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) prevents human immunodeficiency (HIV) among people who inject drugs (PWID). Despite rising HIV incidence and injection drug use (IDU), PrEP use remains low and there is limited research about uptake, adherence, and retention among PWID. Methods The ANCHOR investigation evaluated a community-based care model collocating hepatitis C virus (HCV) treatment, medication for opioid use disorder (OUD), and PrEP in individuals in Washington, DC, and Baltimore, Maryland. PrEP counseling was conducted from HCV treatment day 0 until week 24. Subjects could start any time during this window, were followed for 48 weeks, and were assessed for adherence by self-report and dried blood spot TDF analysis. Results One hundred ninety-eight participants were enrolled, of whom 185 (93%) were HIV negative. Twenty-nine individuals (15.7% of HIV-negative cohort) initiated PrEP. One hundred sixteen participants (62.7%) met 2014 Centers for Disease Control and Prevention (CDC) PrEP criteria due to IDU (82 [44.3%]), sex (9 [4.9%]), or both practices (25 [13.5%]). Providers recommended PrEP to 94 individuals (50.8%), and recommendation was associated with PrEP uptake. Median treatment duration was 104 days (interquartile range, 28–276 days), with 8 participants retained through week 48. Adherence was variable over time by self-report and declined by TDF analysis. No HIV seroconversions occurred. Conclusions This cohort of people with HCV and OUD experienced low uptake of PrEP despite the majority meeting CDC criteria. High rates of disruption and discontinuation, compounded by variable adherence, made TDF/FTC a suboptimal prevention strategy. Emerging modalities like long-acting formulations may address these barriers, but PWID have been excluded from their development to date.

HIV structure and life cycle are highlighted in this chapter. The reader is provided information regarding how virology informs treatment aimed at various stages of the viral life cycle and virology in relation to current and potential drug targets. The chapter goes on to discuss viral classification, viral structure, and viral entry. Reverse transcription and integration are reviewed, and the chapter concludes with an overview of HIV natural history.

This chapter provides an overview of what antiretroviral therapy (ART) is and the current treatment guidelines according to the US Department of Health and Human Services and the International Antiviral Society-USA. Important criteria in selecting an initial treatment regimen are discussed as well as when to switch or simplify the regimen. Factors to consider when selecting an antiretroviral regimen and other information involving ART is presented to the reader via tables.

Outcomes for critically ill people living with human immunodeficiency virus (PLHIV) have changed with the use of antiretroviral therapy (ART). To identify these outcomes and correlates of mortality in a contemporary critically ill cohort in an urban academic medical center in Baltimore, a city with a high burden of HIV, we conducted a retrospective cohort study of individuals admitted to a medical intensive care unit (MICU) at a tertiary care center between 2009 and 2014. PLHIV who were at least 18 years of age with an index MICU admission of ≥24 hours during the 5-year study period were included in this analysis. Data were obtained for participants from the time of MICU admission until hospital discharge and up to 180 days after MICU admission. Logistic regression was used to identify independent predictors of hospital mortality. Between June 2009 and June 2014, 318 PLHIV admitted to the MICU met inclusion criteria. Eighty-six percent of the patients were non-Hispanic Blacks. Poorly controlled HIV was very common with 70.2% of patients having a CD4 cell count200 cells/mm3 within 3 months prior to admission and only 34% of patients having an undetectable HIV viral load. Hospital mortality for the cohort was 17%. In a univariate model, mortality did not differ by demographic variables, CD4 cell count, HIV viral load, or ART use. Regression analysis adjusted by relevant covariates revealed that MICU patients admitted from the hospital ward were 6.4 times more likely to die in hospital than those admitted from emergency department. Other positive predictors were a diagnosis of end-stage liver disease, cardiac arrest, ventilator-dependent respiratory failure, vasopressor requirement, non-Hodgkin lymphoma, and symptomatic cytomegalovirus disease. In conclusion, in this critically ill cohort with HIV infection, most predictors of mortality were not directly related to HIV and were similar to those for the general population.

The global coronavirus disease 2019 pandemic has raised significant concerns of developing rapid, broad strategies to protect the vulnerable population and prevent morbidity and mortality. However, even with an aggressive approach, controlling the pandemic has been challenging, with concerns of emerging variants that likely escape vaccines, nonadherence of social distancing/preventive measures by the public, and challenges in rapid implementation of a global vaccination program that involves mass production, distribution, and execution. In this review, we revisit the utilization of attenuated vaccinations, such as the oral polio vaccine, which are safe, easy to administer, and likely provide cross-protection against respiratory pathogens. We discuss the rationale and data supporting its use and detail description of available vaccines that could be repurposed for curtailing the pandemic.

The 69th World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis, embracing a goal to eliminate hepatitis infection as a public health threat by 2030. This was followed by the World Health Organization's (WHO) global targets for the care and management of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These announcements and targets were important in raising awareness and calling for action; however, tracking countries’ progress towards these elimination goals has provided insights to the limitations of these targets. The existing targets compare a country's progress relative to its 2015 values, penalizing countries who started their programmes prior to 2015, countries with a young population, or countries with a low prevalence. We recommend that (1) WHO simplify the hepatitis elimination targets, (2) change to absolute targets and (3) allow countries to achieve these disease targets with their own service coverage initiatives that will have the maximum impact. The recommended targets are as follows: reduce HCV new chronic cases to ≤5 per 100000, reduce HBV prevalence among 1-year-olds to ≤0.1%, reduce HBV and HCV mortality to ≤5 per 100000, and demonstrate HBV and HCV year-to-year decrease in new HCV- and HBV-related HCC cases. The objective of our recommendations is not to lower expectations or diminish the hepatitis elimination standards, but to provide clearer targets that recognize the past and current elimination efforts by countries, help measure progress towards true elimination, and motivate other countries to follow suit.

A 76-year-old man with acute myelogenous leukemia presented to the hospital with 1 week of left-sided jaw pain and swelling and subjective fevers. The patient had been severely neutropenic (i.e., with an absolute neutrophil count of

Answer: Mucormycosis caused by Rhizopus species. A feared opportunistic invasive fungal infection of the immunocompromised host, mucormycosis typically presents as rhinocerebral, pulmonary, or cutaneous disease in patients with diabetes or hematological malignancies. Rhizopus and Mucor are the most

Background There has been an evolution in the treatment of chronic hepatitis C (HCV) due to highly effective direct-acting antivirals, however, restriction of treatment to medical specialists hinders escalation of HCV treatment. This is particularly true in resource-limited settings (RLS), which disproportionately represent the burden of HCV worldwide. The ASCEND study in Washington, DC, demonstrated that complete task-shifting can safely and effectively overcome a low provider-to-patient ratio and expand HCV treatment. However, this model has not been applied internationally to RLS. Method The validated ASCEND model was translated to an international clinical program in Kigali, Rwanda, aimed at training general medicine providers on HCV management and obtaining HCV prevalence data. Results The didactic training program administered to 11 new HCV providers in Rwanda increased provider’s knowledge about HCV management. Through the training program, 26% of patients seen during the follow-up period were screened for HCV and a prevalence estimate of 2% was ascertained. Of these patients, 30% were co-infected with hepatitis B. Conclusion The ASCEND paradigm can be successfully implemented in RLS to escalate HCV care, in a self-sustaining fashion that educates more providers about HCV management, while increasing the public’s awareness of HCV and access to treatment.

Mixed cryoglobulinemic vasculitis is associated with monoclonal B cell expansion in patients with chronic hepatitis C (HCV) infection. B cell depletion therapy using rituximab, a CD20 monoclonal antibody, has been successful in achieving remission from symptomatic disease. This study investigated whether B cell depletion therapy has an impact on activation of HCV-specific T cell phenotype and function. Nineteen patients with Hepatitis C mixed cryoglobulinemic vasculitis were treated with 4 cycles of rituximab (375 mg/m2 ) and variables were measured 6 months after therapy. Using flow cytometry and Enzyme-Linked Immunospot assay, the number of activated and tissue-like B cells and number of T cells expressing Programmed cell death protein 1 (PD-1), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), and multiple cytokines were measured before and after rituximab therapy. B cell depletion therapy is associated with a significant (P < 0.0001) decline in peripheral T cells with exhaustive phenotype, from pre-therapy to post-therapy-of rituximab (mean ± standard error): CD4+ (16.9 ± 0.9% to 8.9 ± 1.0%) and CD8+ (6.8 ± 0.6% to 3.0 ± 0.5%) T cells expressing PD-1 and CD4+ (11.0 ± 1.0% to 6.1 ± 0.8%) and CD8+ (12.7 ± 0.7% to 6.4 ± 0.4%) T cells expressing TIM-3. In addition, there was a significantly higher percentage of peripheral CD8+ T cells responding to HCV peptide stimulation in vitro secreting IFN-γ (4.55 ± 0.3 to 9.6 ± 1.0 IFN-γ/106 PBMCs, P < 0.0001), and more than one cytokine (1.3 ± 0.1% to 3.8 ± 0.2%, P < 0.0001) after therapy compared to pre-therapy. B cell depletion therapy results in recovery of T cell exhaustion and function in patients with HCV cryoglobulinemic vasculitis.

Background Sustained virologic response (SVR) after hepatitis C virus (HCV) treatment with either Interferon (IFN)-based or IFN-free regimens with direct-acting antivirals (DAAs) has been shown to reduce cardiovascular disease (CVD) events in majority white populations stratified by ASCVD score. However, the effect of IFN-free therapy on lipid profiles after SVR, as an indirect measure of CVD risk, is unknown in Black patients. Methods We evaluated HCV-infected Veterans from the Baltimore VA who were treated with DAAs between 2015-2019. We performed a retrospective analysis comparing lipid profile changes following SVR among those with early stage (F0-F2) fibrosis and advanced liver disease (ALD, F3-F4 fibrosis) using two-tailed paired t-tests. Independent t-tests were used to assess differences in lipid profiles based on fibrosis stage in patients with HIV and Type II Diabetes Mellitus (DM2). Results Of those treated for HCV (n=1,528), 96% (n=1,474) achieved SVR. Demographics are shown in Table 1. Most patients were Black males (75%) and a minority (2.7%) received statin therapy during treatment (Table 1). Of 1,094 patients for whom data was available, an increase in total cholesterol (TC) and LDL (p< 0.01 for both) was seen an average of 17 months after SVR, regardless of fibrosis stage (Figure 1). A significant decrease in triglyceride levels (p=0.04) was also seen in the ALD group after SVR (Figure 1). Mean pre-treatment HCV RNA level was comparable between fibrosis groups (F0-F2: 6.35 logs, F3-F4: 6.37 logs, p=0.46). There were 101 and 436 patients with HIV and DM2, respectively, for whom pre-treatment liver fibrosis data was available. In both groups, there were significant increases in LDL (p=0.008 (HIV), p=0.003 (DM2)) among patients with ALD following SVR. Table 1. Baseline characteristics of treated HCV-infected persons who achieved SVR. Figure 1. Mean lipid profile parameters before and after HCV treatment for patients who achieved SVR. TC was measured a mean of 8.1 months (228 days, SD 333 days) before treatment and 17.4 months (488 days, SD 196 days) after SVR. LDL was measured a mean of 8 months (224 days, SD 284 days) before treatment and 17.5 months (492 days, SD 201 days) after SVR. *=differences in means using paired t-test were statistically significant with p Conclusion In a cohort of mostly Black HCV-infected Veterans, significant increases in TC, driven by increases in LDL, were seen after SVR regardless of fibrosis stage. In addition, patients with ALD and HIV or DM2, who have an inherently higher risk of CVD, had increased LDL levels, suggesting that these patients should be screened and treated for HCV prior to development of ALD. Correlates such as the ASCVD score should be considered in the timing of HCV treatment, in order to reduce the long-term risk of CVD. Disclosures Shyam Kottilil, MD PhD, Arbutus Pharmaceuticals (Grant/Research Support)Gilead Sciences (Grant/Research Support)Merck Inc (Grant/Research Support, Advisor or Review Panel member)

The past five years have seen a revolution in the treatment of chronic hepatitis C, as short duration oral regimens of direct-acting antiviral drugs (DAAs), with nearly 100% cure rates for all genotypes, have replaced longer courses of ribavirin and injected interferon. Although initially very expensive, these DAAs are now becoming available in generic equivalents in countries with large numbers of chronically infected people, such as India. However, a number of obstacles may hinder the delivery of these drugs in resource-limited settings, including lack of access to diagnostic testing and the restriction of treatment to a small number of medical specialists. New approaches are therefore needed to make DAAs available to the estimated 71 million infected people, many of whom disproportionately live in low- or middle-income countries. A recent pilot study (ASCEND) of hepatitis C management in a low-income population in Washington, D.C., demonstrated that trained nurse practitioners, primary care physicians and hepatologists were equally successful in diagnosing and treating patients, indicating that such an approach might be successful in resource-limited regions of the world. Members of the Global Virus Network have received funding to carry out a similar training project in a region of India with a high prevalence of hepatitis C. This paper reviews the challenges of delivering DAA therapy in low- and middle-income countries, describes plans for performing and evaluating the effectiveness of a training program in India, and discusses future needs for the eventual elimination of hepatitis C.

Documentation of antibiotic indication provides helpful information for antimicrobial stewardship, but accuracy is not understood. Review of 396 antibiotic orders in a pediatric ICU and adult medicine step-down unit found 90% agreement between provider-selected indication and independent review. Prompts to enter antibiotic indication during order entry provide largely accurate information.Infect Control Hosp Epidemiol2018;39:111–113

Upon completion of this chapter, the reader should be able to • Demonstrate and apply knowledge about established and evolving science describing HIV virology, both in the cell and in the host. • Effectively counsel and educate patients and their communities regarding HIV treatment.

Hepatitis C virus (HCV) antigen testing is less expensive than quantitative reverse-transcription polymerase chain reaction but has lower sensitivity for very low viral load (VLVL; HCV RNA ≤3000 IU/mL). Currently the benefits of antigen testing for screening are discussed, but data on prevalence and outcomes of persons with VLVL are scarce.We assessed prevalence and predictors of VLVL by logistic regression in treatment-naive participants in the Swiss Hepatitis C Cohort Study. We analyzed if the last viral load after VLVL was low, compared cirrhosis and mortality in persons with and without VLVL, and evaluated the number of samples with VLVL that were reactive by antigen testing.We included 2533 treatment-naive persons with available quantitative HCV RNA testing results. Overall, 133 persons (5.3%) had a VLVL. Age 18-40 years, female sex, and human immunodeficiency virus coinfection were associated with VLVL. Of 72 persons with a viral load available after VLVL, 14% had a VLVL and 17% had spontaneous viral clearance. The prevalence and incidence of cirrhosis and mortality were comparable in persons with and without VLVL; all 24 persons with VLVL and cirrhosis had excessive alcohol consumption or immunosuppression. Overall, 33% of samples with VLVL were reactive by antigen testing.The frequency of VLVL was low. Among the persons who would probably be missed by antigen screening, some had a favorable disease course, but some had immunosuppression and liver cirrhosis. The benefit of HCV antigen testing for screening may be limited by the risk of missing patients with severe liver disease.

Background & Aims Cure rates in response to retreatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) are high, but this regimen has not been studied in patients with a history of poor adherence or treatment interruption, nor in patients with HIV/HCV coinfection. Herein, we aimed to assess the safety and efficacy of this combination in patients with genotype 1 HCV infection who had relapsed following combination direct-acting antiviral (DAA) therapy, regardless of HIV infection or previous treatment course. Methods The RESOLVE study was a multicenter, open-label, phase IIb study investigating the safety, tolerability and efficacy of SOF/VEL/VOX in 77 patients with virologic rebound following combination DAA therapy. Efficacy was defined as HCV RNA below the lower limit of detection 12 weeks after the end of treatment (SVR12), while safety endpoints included the incidence of grade 3 and 4 adverse events (AEs) following treatment, and the proportion of patients who stopped treatment prematurely due to AEs. Results In an intent-to-treat analysis, 70/77 (90.9%, 95% CI 82.1–95.8%) patients achieved SVR12, including 14/17 (82.4%) HIV coinfected participants and 18/22 (81.8%) of those with previous non-completion of DAA therapy. In an analysis of all patients who completed 12 weeks of study medication, 70/71 patients (99%) achieved SVR12. One patient experienced a grade 3 AE, and 4 experienced a grade 4 AE, all unrelated to study participation. Reported AEs were similar in HIV-coinfected patients, and patients receiving dolutegravir-based antiretroviral treatment experienced no clinically significant increases in aminotransferases. Conclusion Retreatment with 12 weeks of SOF/VEL/VOX was safe and effective in patients with relapsed HCV following initial combination DAA-based treatment. Treatment response was not affected by HIV coinfection or previous treatment course. Lay summary Twelve weeks of the combination of direct-acting antivirals (SOF/VEL/VOX) was safe and effective in patients with relapsed hepatitis C virus infection who had previously received combination therapy with direct-acting antivirals. Treatment response was not diminished by HIV coinfection, or non-completion of previous direct-acting antiviral-based therapy.

Background: Hormonal therapy for menopause has been found to be the most efficacious treatment, but it may be associated with adverse effects in some of the women. Rheum rhaponticum root extract (”ERr 731”), which is available worldwide, is a natural, reliable, effective, and well-tolerated remedy for women in perimenopausal women with menopausal symptoms (MSs), but there is no Indian study demonstrating its efficacy, safety, and tolerability till date. Objective: This study aimed to evaluate the efficacy and safety of ERr 731 in alleviating MSs in perimenopausal Indian women. Patients and Methods: In this open-labeled prospective study, 129 perimenopausal women were treated with tablet containing 4 mg of Rr dried root extract once daily for 12 weeks. The Menopause Rating Scale (MRS) II score, endometrial thickness (ET), blood pressure, glycemic status, lipid profile, and high-sensitivity C-reactive protein (hs-CRP) level were periodically assessed and compared. Results: A significant reduction (67% by 12th week) in the mean MRS II score was observed from baseline till the end of 12 weeks (18.1; 95% confidence interval [CI]: 17.0–19.2; P < 0.001). A monotonic reduction in the mean total MRS II score over time was found (1.51 units/week; 95% CI: 1.42–1.60 units/week; P < 0.001) noticeable. There was a reduction in the mean ET from baseline till the end of 12 weeks, although the change was not significant. There were significant reductions in the mean fasting (6.3 mg/dl; 95% CI: 1.7–11.0 mg/dl; P = 0.008) and postprandial (6.3 mg/dl; 95% CI: 1.0–11.7; P = 0.021) blood glucose levels and glycated hemoglobin level (0.30%; 95% CI: 0.085–0.520; P = 0.007) at 12 weeks. No significant changes were noted in terms of blood pressure, lipid profile, and hs-CRP level. The drug was found to be safe. Conclusion: ERr 731 was well tolerated and was found to be efficacious and safe in alleviating MSs in Indian perimenopausal women.

Chronic hepatitis C infection is a major cause of morbidity and mortality in the USA. Treatment options have progressed from interferon-based regimens with moderate efficacy and many adverse effects to the use of directly-acting antiviral agents that are highly efficacious with limited side effect profiles. There is a disproportionate number of patients with end-stage renal disease who are infected with hepatitis C and have an increased risk of cirrhosis and hepatocellular carcinoma, while suffering from a lower quality of life. Renal transplant patients with hepatitis C additionally have an increased risk of graft failure, so treatment is of utmost importance in this population. There are currently several options for hepatitis C treatment in the renal impairment and transplant populations which have similar efficacy compared to the general population; however, the safety of these regimens is still being ascertained. Paritaprevir/ritonavir/ombitasvir and dasabuvir or elbasvir/grazoprevir are good options for use in patients with severe renal impairment or post-renal transplant; however, close monitoring is important given the potential for drug-drug interactions and the need for ribavirin in some of these patients. Several limited recent studies suggest that the efficacy and safety of full doses of sofosbuvir in these populations is not significantly different compared to that in the general population, though the safety of this dosing has not yet been established. Treatment of chronic hepatitis C infection in patients with renal impairment and/or transplant can significantly reduce the morbidity and mortality from cirrhosis and hepatocellular carcinoma, while serving as an effective public health tool to reduce transmission.

Background: Urinary incontinence (UI) affects many older adults. Some of its deleterious consequences include stress, major depression, diminished quality of life, sexual dysfunction, and familial discord. Despite a wealth of research contributions on this topic, the available literature is under representative of ethnic minority older women. Methods: A cross-sectional observational study was conducted by taking a group of 225 females of perimenopausal age group. Patients were assessed clinically for the diagnosis of urinary incontinence and effect on quality of life was assessed. Further testing was done depending on the storage symptoms & voiding symptoms and included residual volume assessment by ultrasound, cystometry, complex urodynamic test and cystoscopy. The data obtained and the socio-demographic data recorded in a structured proforma. The data obtained was assessed, analysed and results were drawn thereafter. Results: In our study the prevalence of UI was found to be 18%. Maximum prevalence was seen in the age group of 61-70 years. Highest numbers were found to have stress incontinence 60.44%, followed by 23.55% of urge, overflow 5.33% and 10.66% mixed symptoms. The impact was equitable over all dimensions measured for QOL, namely activity limitation (28.44%), social interaction limitation (35.11%), sexual activity limitation (16%), financial burden increased (3.55%), emotional upset and distress (16.88%). Conclusions: In the present study, we determined the prevalence of UI among 200 community-dwelling, ethnically diverse older women, discovered that our new UI screener is reliable, and did not find the UI-depression link to be significant.

Background: In female reproductive tract the differential diagnosis of pelvic mass is quite variable because abnormality may arise from gynaecological or non-gynaecological origin. The aim of the present study is to find out the causes why these patients come with large abdominal masses, to find out the risk factors and to do proper management. Methods: This study is a retrospective study of all cases of large abdominal mass All the patient coming with palpable abdominal and pelvic adnexal mass in the gynaecologic OPD were included in the study. Study population included women of all ages and the relevant population of women with treatment for fibroids and ovarian mass. The data was analysed retrospectively and the results were computed accordingly. Results: Incidence of large ovarian mass was found out to be 2.82% and of large fibroid was 2.31%. Our study showed the peak incidence of ovarian tumors in age group more than 40 years. 90.5% of patients were illiterate and only 10 patients were literate. In the study only 8.57% patients had addiction to some drug and all were tobacco chewer. The incidence of benign tumor was 83.33% (commonest being ovarian tumours) and that of malignant tumors is 16.66%. Conclusions: Ultrasound is effective in detecting the abdominal mass, size and type of abdominal mass, so that early diagnosis can be done and treatment can be given as soon as possible. Apart from already established risk factors, obesity and uterine fibroid have an important association.

Background: Pregnancy induced hypertension is one of the most dreaded complication in developing countries. The purpose of this study is to evaluate incidence, risk factors and complications of pre-eclampsia and eclampsia and its relation to serum LDH levels. This was done with a view to making recommendations towards furtherance of objectives of this initiative. Methods: 380 patients with diagnosed eclampsia and preeclampsia were included based on a proforma. Results: Higher grades of proteinuria, higher BP and serum LDH levels >600 IU/L are significantly associated with adverse maternal and fetal outcome. Conclusions: LDH co-relates with adversity of maternal and fetal outcome in eclampsia and pre-eclampsia.

Treatment for hepatitis C has escalated rapidly since the advent of direct-acting antivirals. Although there are highly efficacious, pangenotypic regimens available as standard of care, 5–10% of patients do not achieve virological cure. The recently approved fixed-dose combination of sofosbuvir, velpatasvir and voxilaprevir provides an option for retreatment in patients who have failed prior regimens and have characteristics which make them difficult to treat. This review provides a summary of the evidence for use of Vosevi®, a fixed-dose combination pill for treatment of hepatitis C in treatment-experienced patients.

Background: Hypertensive disorders of pregnancy remains to be a major cause of maternal and fetal morbidity and mortality. The retina offers the unique opportunity to directly observe changes in the vasculature due to preeclampsia. Fundoscopy can be used to prognosticate and assess the severity of disease and offer an optimum time of delivery to improve fetomaternal outcome. There are limited number of studies from northern India assessing the relationship between hypertensive disorders of pregnancy and retinopathy. This study was undertaken to bridge this gap.Methods: This was an observational cohort study undertaken in a tertiary hospital, 225 patients of preeclampsia coming to the department were identified and a structured proforma used to gather relevant information. All patients underwent fundoscopy and were classified into groups on the basis of fundal grade observed. The groups were compared in terms of clinicodemographic variables. Appropriate statistical tests were applied.Results: A total 68% patients had retinal changes of which the most common grade was grade 1 There was a significant rise in the mean systolic and diastolic blood pressure with increasing grade of fundal change. The (p-value 0.001). 65.5% of patients of preeclampsia without severe features (i.e. mild cases) had no retinopathy. None of these patients had grade 3 or 4 changes. In the patients of preeclampsia with severe features, 88.9% cases had varying degrees of retinopathy.Conclusions: As severity of preeclampsia increases, incidence of retinopathy also increases. Fundoscopy is a useful diagnostic aid and should be done to optimize fetomaternal outcome.

Ribavirin, once a staple of hepatitis C treatment, has significant drawbacks, including treatment-limiting side effects, the requirement for intensive laboratory monitoring, the need for frequent dose adjustments, and teratogenicity. These factors make it difficult to escalate ribavirin-based HCV treatment to most infected patients globally. Most studies have shown comparable response rates between ribavirin-inclusive and ribavirin-sparing regimens in uncomplicated patient populations. However, ribavirin is still used in the management of patients who have failed previous therapy as well as those with decompensated liver disease. In this review, we explore the evidence supporting the use of ribavirin in the current climate of hepatitis C treatment with oral combination direct-acting antiviral agents.

Background: Early screening plays a pivotal role in management of breast cancer. Given the socio-economic situation in India, there is a strong felt need for a screening tool which reaches the masses rather than waiting for the masses to reach tertiary centers to be screened. Digital infra-red thermal imaging (DITI) or breast thermography as a screening test offers this possibility and needs to be carefully assessed in Indian scenario.Methods: The study involved 1008 female patients of age 20–60 years that had not been diagnosed of cancer of breast earlier. All the subjects in this population were screened for both the breasts using DITI. Based on the measured temperature gradients (ΔT) in thermograms, the subjects were classified in one of the three groups, normal (ΔT ≤ 2.5), abnormal (ΔT > 2.5, 2.5) underwent triple assessment that consisted of clinical examination, radiological and histopathological examination. Those with normal thermograms were subjected to only clinical examination. Results: Forty nine female breasts had thermograms with temperature gradients exceeding 2.5 and were subjected to triple assessment. Forty one of these which had ΔT ≥ 3 were proven to be having cancer of breast and were offered suitable treatment. Eight thermograms had temperature gradients exceeding 2.5 but less than 3. Most of these were lactating mothers or had fibrocystic breast diseases. As a screening modality, DITI showed sensitivity of 97.6%, specificity of 99.17%, positive predictive value 83.67% and negative predictive value 99.89%. Conclusion: Based on the results of this study involving 1008 subjects for screening of breast cancer, thermography turns out to be a very useful tool for screening. Because it is non-contact, pain-free, radiation free and comparatively portable it can be used in as a proactive technique for detection of breast carcinoma.

HIV is a member of the lentivirus subfamily of retroviruses. Two distinct groups of viruses are pathogenic in humans: HIV-1 and HIV-2. Both are transmitted sexually and known to cause immunodeficiency disease. HIV enters the cell through use of the CD4 receptor and chemokine co-receptors, primarily CCR5 and CXCR4. The viral genome is transcribed from RNA to DNA by reverse transcriptase and integrated into the host genome by integrase. The HIV genome encodes 15 proteins, comprising three categories: structural, regulatory, and accessory. After budding from the host cell, the virus matures into its infectious form through cleavage of viral precursor proteins by protease.

Background Engaging PWID in HCV treatment and monitoring for reinfection is critical to eliminate HCV and improve health in people who use drugs. However, PWID are often marginalized and can be difficult to engage and retain in care. The collocation of HCV treatment with buprenorphine to treat opioid use disorder (OUD) may improve visit adherence in this population. Methods ANCHOR is a single-center study evaluating treatment of HCV in PWID with chronic HCV, OUD, and IDU. Participants receive sofosbuvir/velpatasvir x12 weeks and are offered collocated buprenorphine. HCV visits occur at weeks 4, 12, 24, 48, 72 and 96. Results At screening, the 100 enrolled patients were predominantly male (76%), black (93%), middle-aged (median 57years), injected opioids daily or more (58%), and were not on OAT (67%). Fifty-five (55%) patients were initiated on collocated buprenorphine at some point after day 0. Being on collocated buprenorphine at the time of HCV visit was associated with increased likelihood of visit attendance at weeks 12 (P = 0.002), 24 (P = 0.01), 48 (P = 0.02), 72 (P = 0.003), and 96 (P = 0.04). For patients who attended study visits, being on collocated buprenorphine was associated with a shorter time between planned visit and actual visit at weeks 12 (P = 0.03), 24 (P = 0.04), and 48 (P = 0.04). When looking at patients not on collocated buprenorphine, being on noncollocated opioid agonist therapy vs. not being on OUD treatment did not impact visit adherence. Conclusion Evidence-based treatment of HCV and OUD are critical to improving health in PWID. The collocation of HCV treatment with office-based buprenorphine may improve adherence to visits and visit timing, especially in long-term follow-up. Infectious disease providers should offer collocated buprenorphine as a tool to improve long-term outcomes and engagement in this high-risk population. Disclosures All Authors: No reported Disclosures.

Background People who inject drugs (PWID) have significant morbidity and mortality associated with hepatitis C (HCV); however, harms associated with ongoing injecting drug use (IDU)—such as opioid overdose—may pose a more imminent risk, and often are not addressed as part of HCV treatment. Naloxone distribution is a simple, evidenced-based strategy to reduce mortality associated with opioid overdose. Methods ANCHOR is a single-center study embedded in an urban harm-reduction program evaluating treatment of HCV in PWID with chronic HCV, opioid use disorder (OUD), and IDU. Participants received HCV treatment and were offered collocated buprenorphine. At each study visit, patients self-reported experienced and witnessed overdose and were offered naloxone. Results The 100 enrolled participants are predominantly male (75%), median 57 years, black (93%) and inject opioids at least daily (58%). At baseline, 65% had ever experienced overdose, 91% had ever witnessed an overdose, and 35% had ever administered naloxone. Between day 0 and week 48, 15 patients (15%) experienced overdose; of which, 4 (4%) were fatal. The rate of experienced overdose was 15 overdoses per 100 person-years. In addition, 59 (59%) patients witnessed at least one overdose between day 0 and week 48. Seventy-three patients were dispensed naloxone at least once, and of those who witnessed an overdose, 48 (81%) administered naloxone. Nineteen (40%) patients who administered naloxone had never used naloxone before starting HCV treatment. Conclusion PWID with HCV, OUD, and ongoing IDU have high rates of personal and witnessed overdose during and after HCV treatment. Dispensing naloxone at HCV-related visits is highly acceptable among PWID, and results in high rates of naloxone utilization. To reduce morbidity and mortality in patients and their communities, ID providers should complement treatment of infections by prescribing naloxone for patients with OUD, ideally as part of a comprehensive package of harm reduction and OUD treatment. Disclosures All Authors: No reported Disclosures.

Aim: The aim of this study is to identify the common urinary problems in Indian females, their etiology and symtomatology. Material and Methods: This is a prospective epidemiological study of 703 female patients with urinary problems, who attended the surgery and gynecology OPD (outpatient department) in our institution which is a tertiary referral centre in central India. Result: 58% of patients were middle age (31 - 55) yrs. Burning micturition was the most common urinary complain (607 patients) followed by increased frequency of micturition (309 patients). 68% females took months or even years to take first consultation after appearance of their symptoms. 14% percent of patients suffered from urinary incontinence (stress, urge and mixed). 86% of women had education level below fifth standard. About 58% of females gave birth to 3 or more than 3 issues. About 254 (36%) patients had one or more unassisted delivery at home. Thirty eight percent of patients still remained undiagnosed. More than 50% of undiagnosed females lie in middle age group. 68% of undiagnosed patients took consultation months or years after their symptoms first appeared. Irritative symptoms are the most common presenting complains of these undiagnosed patients followed by pain in abdomen. Around 60% of patients had history of either mental distress, domestic violence or any neuropschiatric disease. This study only gives us an idea about the urinary problems faced by females and their probable causative factors. Many more studies need to be done involving multidisciplinary approach in order to benefit this section of our society.

Background People who inject drugs (PWID) have an increased risk for HIV, and HCV infection may foreshadow HIV acquisition in current epidemics. Studies of PWID have demonstrated a desire to obtain HCV treatment; however, use of pre-exposure prophylaxis (PrEP) in this population has not been well studied. Methods The ANCHOR study is an ongoing single-center study evaluating treatment of HCV in PWID. Enrolled patients have chronic HCV, opioid use disorder, and inject opioids. Patients are treated with sofosbuvir/velpatasvir and offered PrEP. Patients complete baseline community health worker (CHW)-administered surveys, physician assessment of PrEP eligibility, and are offered PrEP uptake. Results Of 89 enrolled patients, 49 (55%) met CDC criteria for PrEP, and 21 (24%) patients started PrEP. Reasons for not starting PrEP are in Figure 1. Though most patients are black (n = 82, 92.1%) and heterosexual (n = 81, 91%), these patients were less likely to start PrEP (P = 0.0068 and P = 0.0283, respectively). Baseline interest in starting PrEP was correlated with uptake (P = 0.0023), however, self-identifying as high-risk for HIV acquisition or meeting CDC criteria for PrEP were not. Though more patients endorsed sharing of injection equipment to a CHW than a physician (17% vs. 7%), endorsement to a physician rather than CHW was associated with starting PrEP (P = 0.0307). To date, 13 (62%) patients discontinued PrEP, 7 (54%) due to side effects. Conclusion Preliminary results of the ANCHOR study support that engagement in HCV care provides an opportunity for PWID to participate in PrEP intake; however, we found relatively low uptake in these patients, despite over half meeting CDC criteria. Our findings highlight the importance of counseling by physicians for initiation of PrEP, and suggest that improved communication between CHW and physician regarding risk behaviors could improve uptake. These data also reinforce that patients must be counseled and managed for side effects in order to retain them in care. Given the increasing opioid epidemic in the United States, more consideration needs to be given regarding how to incorporate PrEP into care, and how to effectively target and improve interest in PrEP for high-risk populations with poor uptake, including minorities and PWID. Disclosures C. Gross, Merck, Pfizer, Johnson and Johnson: Shareholder, stock. E. Rosenthal, Gilead Sciences, Merck: Grant Investigator, Grant recipient.

Background: There is a massive public interest and debate on both the cause and appropriateness of increasingly employing a surgical procedure to short circuit or entirely bypass labour and delivery. The indications of caesarean sections vary among institutions as there is no standard classification system exists for indications of C-Section. Present study analysed pattern of caesarean section at two tertiary centre in Madhya Pradesh, India.Methods: A structured proforma was filled up for every case and results were recorded on excel sheet. All the cases included in study were further divided in group 1 (deliveries conducted in year 2014-2015 at Govt. Medical College Indore, M.P.), group 2 (deliveries conducted at Govt. Medical College Rewa at same time. Comparative analysis between study group1 and group 2 was done using Pearson Chi square test.Results: In group 1 there were 10525 deliveries out of which 3705 were delivered by caesarean section (35.2%), in group 2 there were 8674 deliveries out of which 1182 were delivered by caesarean section (13.6%). This difference in caesarean section at both medical college may be due to the more no. of referrals from the periphery to the medical college Indore and having more no of private institutions and district hospital which cater the normal delivery.Conclusions: There is a reliable and reproducible framework is required for audit and analysis of Caesarean section trends in specific obstetric subgroups to permit comparisons of practice between different institutions and over time in the same institution.