Adjuvant Topical Interferon Alpha 2b for the Treatment of Monkeypox Ocular Manifestations.

PURPOSE: The aim of this study was to report a case of ocular Mpox that responded favorably to treatment with topical interferon and oral doxycycline. METHODS: This is a case report of a previously healthy 24-year-old woman who developed a pustular rash, headache, fever, arthralgia, sore throat, and asthenia 3 weeks before attending to our clinic. Her main complaint at the moment of the visit was pain, photophobia, foreign body sensation, blurred vision, red eye, and discharge on the left eye. The slit-lamp examination of the left eye showed severe conjunctival hyperemia associated with tarsal follicles, 360 degrees ciliary injection, diffuse corneal epithelial edema with white linear epithelial infiltrates, pigmented and nonpigmented keratic precipitates, and two 1-mm peripheral corneal ulcers with white infiltrates, associated with positive fluorescein staining. Anterior chamber cellularity and flare were mildly present. RESULTS: Mpox with ocular manifestations diagnosis was confirmed by real-time quantitative reverse transcription polymerase chain reaction assay (qRT-PCR) testing; samples were taken from corneal, conjunctival, and nasopharynx swab as well as a skin scab. Topical interferon alpha 2b 1 MIU/mL every 6 hours for 1 month and oral doxycycline 100 mg BID were administered along with other medications with consequent decrease of inflammation and malaise symptoms 1 week later, associated with uncorrected visual acuity improvement. CONCLUSIONS: Alternative and efficacious treatment options for Mpox ocular manifestations are needed to prevent further disease progression and sequelae in countries with no access to the gold-standard therapy. Topical interferon alpha 2b and oral doxycycline have shown adequate response as shown with this patient.

Incomplete Antiretroviral Therapy Adherence Is Associated with Lower CD4-CD8 Ratio in Virally Suppressed Patients with HIV Infection in Mexico.

Suboptimal adherence to antiretroviral therapy (ART) in people with HIV, even during sustained viral suppression, is associated with persistent inflammation, immune activation, and coagulopathy. Persistently low CD4-CD8 Ratio has been also associated with residual inflammation, is a good predictor of increased risk of death and more widely available than inflammatory biomarkers. We tested the hypothesis that the CD4-CD8 Ratio is associated with ART adherence during periods of complete viral suppression. We used the Medication Possession Ratio based in pharmacy registries as measure of adherence and time-varying, routine care CD4 and CD8 measurements as outcome. We used a linear mixed model for longitudinal data, including fixed effects for sex, age, education, date of ART initiation, AIDS-related conditions, and baseline CD4 to model the outcome. In 988 adults with a median follow-up of 4.13 years, higher ART adherence was independently associated with a modest increase in CD4-CD8. For each increasing percentage point in adherence, the CD4-CD8 Ratio increased 0.000857 (95% confidence interval [CI] -0.000494 to 0.002209, p = .213731) in the first year after achieving viral suppression; 0.001057 (95% CI 0.000262-0.001853, p = .009160) in years 1 to 3; 0.000323 (95% CI -0.000448 to 0.001095, p = .411441) in years 3 to 5; and 0.000850 (95% CI 0.000272-0.001429, p = .003946) 5-10 years after achieving viral suppression. The magnitude of the effect of adherence over CD4-CD8 Ratios varied over time and by baseline CD4 count, with increasing adherence having a larger effect early after ART initiation in people with higher baseline CD4 (>500 cells/µL) and in later years in people with lower baseline CD4 count (≥200 cells/µL). Our findings expand on previous evidence suggesting that the benefits of optimal adherence to modern ART regimens goes beyond maintaining viral suppression. These results highlight the importance of including objective measurements of adherence as part of routine care, even in patients with complete HIV suppression over long-term follow-up.

Gaps in the continuum of care in HIV-positive adults and the need for caution in those returning to care after loss to follow-up.

Loss to follow-up (LTFU) and interruption of antiretroviral therapy (ART) are associated with worse outcomes in people with HIV (PWH). Little is known about gaps in the continuum of care. We conducted a retrospective cohort study including adult PWH with at least one clinical visit during 2000-2017. Three groups of care were defined: those constantly retained in care (constantly-RIC), definitively LTFU (dLTFU), and those who returned to care (RTC) after being LTFU for 1 year. We analyzed characteristics of individuals at enrollment. Among 2967 patients, 1565 (53%) were constantly-RIC, 826 (28%) dLTFU, and 576 (19%) RTC. CD4+ ≥350 cells/µL at enrollment was more frequent in RTC patients (43% vs 28% in both constantly-RIC and dLTFU groups, p < 0.01). Time since enrollment to ART initiation was longer in dLTFU (3.3 weeks) and RTC groups (6.0 weeks) in comparison with constantly-RIC patients (2.0 weeks, p < 0.01). Multivariate analysis showed significant differences between groups. Older and ART-naïve patients at enrollment were less likely to have gaps in the continuum of care. Those with non-MSM transmission were less likely to RTC. Patients with CD4+ ≥350 cells/µL at enrollment were more likely to reengage in care. Interventions should be tailored for those at risk of LTFU.

Risk factors associated with HCV co-infection amongst MSM and transgender women living with HIV in Mexico City: A case-control study.

INTRODUCTION AND OBJECTIVES: Hepatitis C virus infection (HCV) is a major cause of co-morbidity in people living with HIV (PLWHIV). The modes of HCV transmission in the local population of PLWHIV are still unclear. We conducted this study to identify risk factors for HCV transmission amongst PLWHIV in central Mexico. MATERIAL AND METHODS: We enrolled HIV/HCV co-infected cases and HIV controls receiving care in two outpatient clinics in Mexico City. Structured questionnaires were applied, covering demographics, history of percutaneous exposures, sexual behaviors, self-reported STD and recreational drug use. The statistical analysis for between-group comparisons were multivariate logistic regression models to assess the risk factors associated with HCV co-infection. We limited the final analysis to men who have sex with men (MSM) to avoid confounders potentially related to HCV acquisition in other populations. RESULTS: Three hundred and thirty-four MSM with HIV (175 with HCV co-infection and 159 without) were analysed. We did not identify percutaneous exposures as risk factors for HCV. Intravenous drug use (IVDU) occurred in two cases and one control case. Risk factors independently associated with acquiring HCV co-infection were: history of an ulcerative STD (aOR=2.65, 95%CI=1.44-4.88), a HCV positive partner (aOR=5.25, 95%CI=2.78-9.91), having practiced insertive fisting (aOR=2.62, 95%CI=1.01-6.90), and rectal administration of drugs during sex (aOR=2.46, 95%CI=1.25-4.84). CONCLUSIONS: Risky sexual behaviors and chemsex seem to be the main drivers of HIV/HCV co-infection amongst PLWHIV in Central Mexico. IVDU and percutaneous exposures have a minor role in the local HCV epidemic. These findings highlight the importance of testing for HCV in sexually active MSMs.

Clinical effects of durability of immunosuppression in virologically suppressed ART-initiating persons with HIV in Latin America. A retrospective cohort study.

Background: Clinical outcomes are rarely studied in virologically suppressed people living with HIV (PWH) and incomplete CD4 recovery. To explore whether time living with severe immunosuppression predict clinical outcomes better than baseline or time updated CD4, we estimated the association between cumulative percentage of time with CD4 <200 cells/µL during viral suppression (VS) (%tCD4<200), and mortality and comorbidities during 2000-2019. Methods: In a retrospective cohort analysis, we followed PWH initiating ART in Latin America from first VS (HIV-RNA<200 copies/µL) to death, virological failure or loss to follow-up. We fit Cox models to estimate risk of death and/or AIDS-defining and serious non-AIDS-defining events (ADE and SNADE -cancer, cardiovascular, liver, and renal diseases) by %tCD4<200 (continuous variable). We predicted survival probabilities for each event and calculated risks of hypothetical cases of different %tCD4<200. Findings: In 8,369 patients with 34·9 months of follow-up (median, IQR: 16·7, 69·1), 4,274 (51%) started ART with CD4<200 cells/µL. Median %tCD4<200 was 0% (IQR: 0, 15%). We identified 195 (2·3%) deaths and 584 (7·2%) patients with ADE/SNADE. For an increased %tCD4<200 of 15% (e.g., 15% vs. 0%), the adjusted relative hazard (aHR) of death was 1·27 (95% confidence interval [CI]: 1·19 - 1·35), of ADE/SNADE was 1·13 (95%CI: 1·09 - 1·17), of SNADE was 0·96 (95%CI: 0·89 - 1·02) and of death/ADE/SNADE was 1·11 (95%CI: 1·07 - 1·14). Estimates were similar after adjusting for time updated CD4 count. Interpretation: In virologically suppressed PWH, increased time living with severe immunosuppression had an increased risk of death and ADE/SNADE in this Latin American cohort, independently of time updated CD4 count. Funding: This work was supported by the NIH-funded Caribbean, Central and South America network for HIV epidemiology (CCASAnet, U01AI069923), a member cohort of the International Epidemiologic Databases to Evaluate AIDS (leDEA). This award is funded by the following institutes: Eunice Kennedy Shriver National Institute Of Child Health & Human Development (NICHD), National Cancer Institute (NCI), National Institute Of Allergy And Infectious Diseases (NIAID), National Institute Of Mental Health (NIMH), the National Heart, Lung, and Blood Institute (NHLBI), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and the Fogarty International Center (FIC). Specific funding was provided from the Fogarty International Center (FIC) for lead author, Yanink Caro-Vega, for the Fogarty-IeDEA Mentorship Program (FIMP).

Seroepidemiology of SARS-CoV-2 in healthcare personnel working at the largest tertiary COVID-19 referral hospitals in Mexico City.

INTRODUCTION: We performed a longitudinal SARS-CoV-2 seroepidemiological study in healthcare personnel of the two largest tertiary COVID-19 referral hospitals in Mexico City. METHODS: All healthcare personnel, including staff physicians, physicians in training, nurses, laboratory technicians, researchers, students, housekeeping, maintenance, security, and administrative staff were invited to voluntarily participate, after written informed consent. Participants answered a computer-assisted self-administered interview and donated blood samples for antibody testing every three weeks from October 2020 to June 2021. RESULTS: A total of 883 participants (out of 3639 registered employees) contributed with at least one blood sample. The median age was 36 years (interquartile range: 28-46) and 70% were women. The most common occupations were nurse (28%), physician (24%), and administrative staff (22%). Two hundred and ninety participants (32.8%) had a positive-test result in any of the visits, yielding an overall adjusted prevalence of 33.5% for the whole study-period. Two hundred and thirty-five positive tests were identified at the baseline visit (prevalent cases), the remaining 55 positive tests were incident cases. Prevalent cases showed associations with both occupational (institution 2 vs. 1: adjusted odds ratio [aOR] = 2.24, 95% confidence interval [CI]: 1.54-3.25; laboratory technician vs. physician: aOR = 4.38, 95% CI: 1.75-10.93) and community (municipality of residence Xochimilco vs. Tlalpan: aOR = 2.03, 95% CI: 1.09-3.79) risk-factors. The incidence rate was 3.0 cases per 100 person-months. Incident cases were associated with community-acquired risk, due to contact with suspect/confirmed COVID-19 cases (HR = 2.45, 95% CI: 1.21-5.00). CONCLUSIONS: We observed that between October 2020 and June 2021, healthcare workers of the two largest tertiary COVID-19 referral centers in Mexico City had similar level of exposure to SARS-CoV-2 than the general population. Most variables associated with exposure in this setting pointed toward community rather than occupational risk. Our observations are consistent with successful occupational medicine programs for SARS-CoV-2 infection control in the participating institutions but suggest the need to strengthen mitigation strategies in the community.

Exceptional T CD4+ Recovery Post-antiretroviral Is Linked to a Lower HIV Reservoir with a Specific Immune Differentiation Pattern.

We present a cohort of individuals who reached CD4+ T cell counts of greater than 1,000 cells/mm3 (Hypers) after starting antiretroviral treatment (ART) and compared them with those who reached between 350 and 999 CD4+ T cells/mm3 (Concordants). Demographic data, immune recovery kinetics, T CD4+ subset phenotypes, and integrated HIV DNA were analyzed. Data from individuals living with HIV on their first ART regimen and after 48 months of follow-up were obtained. Immune phenotype by Flow Cytometry analysis on whole blood was performed, cytokines were measured, and integrated HIV-1 DNA was measured by polymerase chain reaction. From a total of 424 individuals, 26 Hypers (6.1%), 314 Concordants (74.1%), and 84 (19.8%) discordants were identified. Hypers had a higher proportion of CD4+-naive (Nv) T cells (37.6 vs. 24.8, p < .05), and a low proportion of CD4+ effector memory T cells (27.9 vs. 39.4, p < .05), with similar results found in CD8+ T cells. Hypers demonstrated a higher percentage of CD4+CD45RA+CD31neg cells with a lower response to interleukin-2 stimulation and a lower integrated HIV-1 DNA/CD4 ratio (1.2 vs. 2.89, p < .05). In Hypers, T cell recovery occurs very early after initiation of ART. Following this initial recovery state, their CD4+ T cell level homeostasis seems to be driven by nonthymic-central-Nv cells. This exceptional recovery is associated with a lower HIV reservoir, which may be related to an increase in noninfected CD4+ T cells. These patients could then be eligible candidates for cure trials.

Retention in Care, Mortality, Loss-to-Follow-Up, and Viral Suppression among Antiretroviral Treatment-Naïve and Experienced Persons Participating in a Nationally Representative HIV Pre-Treatment Drug Resistance Survey in Mexico.

We describe associations of pretreatment drug resistance (PDR) with clinical outcomes such as remaining in care, loss to follow-up (LTFU), viral suppression, and death in Mexico, in real-life clinical settings. We analyzed clinical outcomes after a two-year follow up period in participants of a large 2017-2018 nationally representative PDR survey cross-referenced with information of the national ministry of health HIV database. Participants were stratified according to prior ART exposure and presence of efavirenz/nevirapine PDR. Using a Fine-Gray model, we evaluated virological suppression among resistant patients, in a context of competing risk with lost to follow-up and death. A total of 1823 participants were followed-up by a median of 1.88 years (Interquartile Range (IQR): 1.59-2.02): 20 (1%) were classified as experienced + resistant; 165 (9%) naïve + resistant; 211 (11%) experienced + non-resistant; and 1427 (78%) as naïve + non-resistant. Being ART-experienced was associated with a lower probability of remaining in care (adjusted Hazard Ratio(aHR) = 0.68, 0.53-0.86, for the non-resistant group and aHR = 0.37, 0.17-0.84, for the resistant group, compared to the naïve + non-resistant group). Heterosexual cisgender women compared to men who have sex with men [MSM], had a lower viral suppression (aHR = 0.84, 0.70-1.01, p = 0.06) ART-experienced persons with NNRTI-PDR showed the worst clinical outcomes. This group was enriched with women and persons with lower education and unemployed, which suggests higher levels of social vulnerability.

Clinical Characteristics and Mortality of Health-Care Workers With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Mexico City.

BACKGROUND: We evaluated the risk of death for health-care workers (HCW) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Mexico City during the coronavirus disease 2019 (COVID-19) pandemic, and describe the associated factors in hospitalized HCW, compared with non-HCW. METHODS: We analyzed data from laboratory-confirmed SARS-CoV-2 cases registered from 27 February-31 August 2020 in Mexico City's public database. Individuals were classified as non-HCW or HCW (subcategorized as physicians, nurses, and other HCW). In hospitalized individuals, a multivariate logistic regression model was used to analyze the potential factors associated with death and compare mortality risks among groups. RESULTS: A total of 125 665 patients were included. Of these, 13.1% were HCW (28% physicians, 38% nurses, and 34% other HCW). Compared with non-HCW, HCW were more frequently female, were younger, and had fewer comorbidities. Overall, 25 771 (20.5%) were treated as inpatients and 11 182 (8.9%) deaths were reported. Deaths in the total population (9.9% vs 1.9%, respectively; P < .001) and in hospitalized patients (39.6% vs 19.3%, respectively; P < .001) were significantly higher in non-HCW than in HCW. In hospitalized patients, using a multivariate model, the risk of death was lower in HCW in general (odds ratio [OR], 0.53) than in non-HCW, and the risks were also lower by specific occupation (OR for physicians, 0.60; OR for nurses, 0.29; OR for other HCW 0.61). CONCLUSIONS: HCW represent an important proportion of individuals with SARS-CoV-2 infection in Mexico City. While the mortality risk is lower in HCW compared to non-HCW, a high mortality rate in hospitalized patients was observed in this study. Among HCW, nurses had a lower risk of death compared to physicians and other HCW.

CLINICAL AND EPIDEMIOLOGICAL CHARACTERISTICS OF PATIENTS DIAGNOSED WITH COVID-19 IN A TERTIARY CARE CENTER IN MEXICO CITY: A PROSPECTIVE COHORT STUDY.

BACKGROUND: Regional information regarding the characteristics of patients with coronavirus disease (COVID)-19 is needed for a better understanding of the pandemic. OBJECTIVE: The objective of the study to describe the clinical features of COVID-19 patients diagnosed in a tertiary-care center in Mexico City and to assess differences according to the treatment setting (ambulatory vs. hospital) and to the need of intensive care (IC). METHODS: We conducted a prospective cohort, including consecutive patients with COVID-19 from February 26, 2020 to April 11, 2020. RESULTS: We identified 309 patients (140 inpatients and 169 outpatients). The median age was 43 years (interquartile range, 33-54), 59.2% men, and 18.6% healthcare workers (12.3% from our center). The median body mass index (BMI) was 29.00 kg/m2 and 39.6% had obesity. Compared to outpatients, inpatients were older, had comorbidities, cough, and dyspnea more frequently. Twenty-nine (20.7%) inpatients required treatment in the IC unit (ICU). History of diabetes (type 1 or 2) and abdominal pain were more common in ICU patients compared to non-ICU patients. ICU patients had higher BMIs, higher respiratory rates, and lower room-air capillary oxygen saturations. ICU patients showed a more severe inflammatory response as assessed by white blood cell count, neutrophil and platelet count, C-reactive protein, ferritin, procalcitonin, and albumin levels. By the end of the study period, 65 inpatients had been discharged because of improvement, 70 continued hospitalized, and five had died. CONCLUSIONS: Patients with comorbidities, either middle-age obese or elderly complaining of fever, cough, or dyspnea, were more likely to be admitted. At admission, patients with diabetes, high BMI, and clinical or laboratory findings consistent with a severe inflammatory state were more likely to require IC.

Frequency of non-communicable diseases in people 50 years of age and older receiving HIV care in Latin America.

BACKGROUND: A growing population of older adults with HIV will increase demands on HIV-related healthcare. Nearly a quarter of people receiving care for HIV in Latin America are currently 50 years or older, yet little is known about the frequency of comorbidities in this population. We estimated the prevalence and incidence of non-communicable diseases (NCDs) among people 50 years of age or older (≥50yo) receiving HIV care during 2000-2015 in six centers affiliated with the Caribbean, Central and South American network for HIV epidemiology (CCASAnet). METHODS: We estimated the annual prevalence, and overall prevalence and incidence of cardiovascular diseases, diabetes, hypertension, dyslipidemia, psychiatric disorders, chronic liver and renal diseases, and non-AIDS-defining cancers, and multimorbidity (more than one NCD) of people ≥50yo receiving care for HIV. Analyses were performed according to age at enrollment into HIV care (<50yo and ≥50yo). RESULTS: We included 3,415 patients ≥50yo, of whom 1,487(43%) were enrolled at age ≥50 years. The annual prevalence of NCDs increased from 32% to 68% and multimorbidity from 30% to 40% during 2000-2015. At the last registered visit, 53% of patients enrolled <50yo and 50% of those enrolled ≥50yo had at least one NCD. Most common NCDs at the last visit in each age-group at enrollment were dyslipidemia (36% in <50yo and 28% in ≥50yo), hypertension (17% and 18%), psychiatric disorders (15% and 10%), and diabetes (11% and 12%). CONCLUSIONS: The prevalence of NCDs and multimorbidity in people ≥50 years receiving care for HIV in CCASAnet centers in Latin America increased substantially in the last 15 years. Our results make evident the need of planning for provision of complex, primary care for aging adults living with HIV.

Clinical and epidemiological characteristics of patients diagnosed with covid-19 in a tertiary care center in Mexico City: a prospective cohort study

ABSTRACT Background: Regional information regarding the characteristics of patients with coronavirus disease (COVID)-19 is needed for a better understanding of the pandemic. Objective: The objective of the study to describe the clinical features of COVID-19 patients diagnosed in a tertiary-care center in Mexico City and to assess differences according to the treatment setting (ambulatory vs. hospital) and to the need of intensive care (IC). Methods: We conducted a prospective cohort, including consecutive patients with COVID-19 from February 26, 2020 to April 11, 2020. Results: We identified 309 patients (140 inpatients and 169 outpatients). The median age was 43 years (interquartile range, 33-54), 59.2% men, and 18.6% healthcare workers (12.3% from our center). The median body mass index (BMI) was 29.00 kg/m2 and 39.6% had obesity. Compared to outpatients, inpatients were older, had comorbidities, cough, and dyspnea more frequently. Twenty-nine (20.7%) inpatients required treatment in the IC unit (ICU). History of diabetes (type 1 or 2) and abdominal pain were more common in ICU patients compared to non-ICU patients. ICU patients had higher BMIs, higher respiratory rates, and lower room-air capillary oxygen saturations. ICU patients showed a more severe inflammatory response as assessed by white blood cell count, neutrophil and platelet count, C-reactive protein, ferritin, procalcitonin, and albumin levels. By the end of the study period, 65 inpatients had been discharged because of improvement, 70 continued hospitalized, and five had died. Conclusions: Patients with comorbidities, either middle-age obese or elderly complaining of fever, cough, or dyspnea, were more likely to be admitted. At admission, patients with diabetes, high BMI, and clinical or laboratory findings consistent with a severe inflammatory state were more likely to require IC.

High prevalent human papillomavirus infections of the oral cavity of asymptomatic HIV-positive men.

BACKGROUND: Incidence of anal and oral infections with Human Papillomavirus (HPV) is increasing, particularly among Human Immunodeficiency Virus-positive (HIV+) men. HPV type 16 has exhibited the highest incidence and only limited data is available on other prevalent types, variants of HPV16, as well as associated factors. We were interested in identifying prevalent HPV types, variants of type 16, as well as factors associated with HPV16 infections in the oral cavity of HIV+ men who have sex with men (MSM). METHODS: A cross-sectional study of oral cavity samples from HIV+ MSM, that in a previous study were identified as positive for HPV16 in the anal canal. Cells from the oral cavity (102 samples, paired with 102 from the anal canal of same patient) were used to extract DNA and detect HPV infections using INNO-LiPA HPV Genotyping Extra II, and PCR. From these, 80 samples (paired, 40 anal and 40 oral) were used to identify variants of type 16 by sequencing. Statistical differences were estimated by the X2 test, and p values equal to or less than 0.05 were considered significant. SPSS ver. Twenty-four statistical software (IBM Corp) was used. RESULTS: We found a high prevalence of High-Risk HPV (HR-HPV) and Low-Risk HPV (LR-HPV). Patients were positive in the oral cavity for HR types; 16, 39 and 18 (80.4, 61.8 and 52.9% respectively) and LR types 11 and 6 (53.9 and 34.3% respectively). Surprisingly, only European variants of type 16 were found in the oral cavity, although American Asian (22.5%) and African (2.5%) variants were identified in the anal canal. The analysis showed that CD4 counts could be the most important risk factor associated with HR-HPV infections in the oral cavity, anal canal or both anatomical regions. The risk of infection of the oral cavity with type 18 increased in men diagnosed with HIV for more than 6 years. CONCLUSIONS: Prevalence of both HR and LR HPV's in the oral cavity of Mexican HIV+ MSM is very high. The fact that only European variants of HPV16 were found in the oral cavity suggest a possible tropism not previously described.

The Population Impact of Late Presentation With Advanced HIV Disease and Delayed Antiretroviral Therapy in Adults Receiving HIV Care in Latin America.

Late presentation to care and antiretroviral therapy (ART) initiation with advanced human immunodeficiency virus (HIV) disease are common in Latin America. We estimated the impact of these conditions on mortality in the region. We included adults enrolled during 2001-2014 at HIV care clinics. We estimated the adjusted attributable risk (AR) and population attributable fraction (PAF) for all-cause mortality of presentation to care with advanced HIV disease (advanced LP), ART initiation with advanced HIV disease, and not initiating ART. Advanced HIV disease was defined as CD4 of <200 cells/µL or acquired immune deficiency syndrome. AR and PAF were derived using marginal structural models. Of 9,229 patients, 56% presented with advanced HIV disease. ARs of death for advanced LP were 86%, 71%, and 58%, and PAFs were 78%, 58%, and 43% at 1, 5, and 10 years after enrollment. Among people without advanced LP, ARs of death for delaying ART were 39%, 32%, and 37% at 1, 5, and 10 years post-enrollment and PAFs were 20%, 14%, and 15%. Among people with advanced LP, ART decreased the hazard of death by 63% in the first year after enrollment, but 93% of these started ART; thus universal ART among them would reduce mortality by only 10%. Earlier presentation to care and earlier ART initiation would prevent most HIV deaths in Latin America.

Bilateral Proximal Forearm Transplantation: Case Report at 7 Years.

BACKGROUND: Although return of function has been reported in patients undergoing proximal forearm transplantations (PFTs), reports of long-term function are limited. In this study, we evaluated the clinical progress and function 7 years postoperatively in a patient who underwent bilateral PFT. CASE PRESENTATION: A 58-year-old man underwent bilateral PFT in May 2012. Transplantation involved all of the flexor and extensor muscles of the forearm. Neurorrhaphies of the median, ulnar, and radial nerves were epineural and 7 cm proximal to the elbow. Immunosuppressive maintenance medications during the first 3 years postoperatively were tacrolimus, mycophenolate, and steroids, and later, tacrolimus, sirolimus, and steroids. Forearm function was evaluated annually using the Disabilities of the Arm, Shoulder, and Hand; Carroll; Hand Transplantation Score System; Short Form-36; and Kapandji scales. We also evaluated his grip and pinch force. RESULTS: Postoperatively, the patient developed hypertriglyceridemia and systemic hypertension. He experienced 6 acute rejections, and none were resistant to steroids. Motor function findings in his right/left hand were: grip strength: 10/13 kg; key pinch: 3/3 kg; Kapandji score: 6/9 of 10; Carroll score: 66/80; Hand Transplantation Score System score: 90/94. His preoperative Disabilities of the Arm, Shoulder, and Hand score was 50 versus 18, postoperatively; his Short Form-36 score was 90. This function improved in relation with the function reported in the second year. CONCLUSIONS: Seven years following PFT, the patient gained limb strength with a functional elbow and wrist, although with diminished digital dexterity and sensation. Based on data presented by other programs and our own experience, PFT is indicated for select patients.

III. THE ROLE OF THE RESEARCH ETHICS COMMITTEES IN THE REGULATION OF PHARMA-SPONSORED STUDIES.

Participants of Pharma-sponsored research are exposed to risks, benefits, and uncertainties that do not occur in other forms of clinical studies. Ethics committees represent the subjects' first line of protection. This responsibility begins with the study review and ends after all study subjects finish the intervention. The objective of this paper is to review the most common controversial issues found in Pharma-sponsored studies. Potential solutions are proposed to prevent or resolve the polemical aspects. However, different challenges will be faced in the near future (e.g., when new therapies reach their late stage of development). All parties involved in research should work together to guarantee the protection of participants, the paramount principle on which clinical investigation is based. Pharma-sponsored research is a crucial driver to develop and implement innovative approaches to improve the informed consent process and the execution of the studies.

III. The role of the Research Ethics Committees in the regulation of Pharma-Sponsored studies

Participants of Pharma-sponsored research are exposed to risks, benefits, and uncertainties that do not occur in other forms of clinical studies. Ethics committees represent the subjects’ first line of protection. This responsibility begins with the study review and ends after all study subjects finish the intervention. The objective of this paper is to review the most common controversial issues found in Pharma-sponsored studies. Potential solutions are proposed to prevent or resolve the polemical aspects. However, different challenges will be faced in the near future (e.g., when new therapies reach their late stage of development). All parties involved in research should work together to guarantee the protection of participants, the paramount principle on which clinical investigation is based. Pharma-sponsored research is a crucial driver to develop and implement innovative approaches to improve the informed consent process and the execution of the studies.