Effects of Semaglutide on Muscle Structure and Function in the SLIM LIVER Study.

BACKGROUND: Semaglutide, a GLP-1 receptor agonist, is highly effective for decreasing weight. Concomitant loss of muscle mass often accompanies weight loss and may have consequences on muscle function. METHODS: This is a secondary analysis from the SLIM LIVER (ACTG A5371) study, a single-arm study of semaglutide in people with HIV (PWH) with metabolic dysfunction-associated steatotic liver disorder (MASLD). Participants received subcutaneous semaglutide for 24 weeks (titrated to 1 mg/week by week 4). Psoas volume and fat fraction were assessed from liver magnetic resonance imaging and physical function by 10-time chair rise test and 4m gait speed. Mean change from baseline to week 24 was estimated with linear regression modeling. RESULTS: 51 PWH enrolled; muscle measures were available from 46 participants. The mean age was 50 (standard deviation [SD] 11) years and BMI 35.5 (5.6) kg/m2, 43% were women, 33% Black, and 39% Hispanic/Latino. Psoas muscle volume decreased by 9.3% (95% confidence interval [CI]: -13.4, -5.2; p<0.001) over 24 weeks but psoas muscle fat did not significantly change (-0.42%, CI: -1.00, 0.17; p=0.16). Chair rise and gait speed had non-significant improvements of 1.27 seconds (CI: -2.7, 0.10) and 0.05 m/sec (CI: -0.01, 0.10), respectively (both p>0.07). The prevalence of slow gait speed (< 1 m/sec) decreased from 63% to 46% (p=0.029). CONCLUSIONS: In PWH receiving low-dose semaglutide for MASLD, despite decreased psoas muscle volume, there was no significant change in physical function. This suggests that function was maintained despite significant loss of muscle concomitant with weight loss.

Development and content validity of EVAD: A novel tool for evaluating and classifying the severity of adverse events for psychotherapeutic clinical trials.

OBJECTIVE: Develop and obtain content validity of a new tool for Evaluating and Classifying the Severity of Adverse Events for Psychotherapeutic Clinical Trials (EVAD). METHOD: Study of the development process of EVAD in four stages: (1) identify the domain and concept definition through a literature review, (2) instrument design, (3) expert judgment of the EVAD items through Gwent's concordance coefficient, and (4) applicability. RESULTS: In the absence of a consistent conceptual framework of adverse events in psychotherapeutic clinical trials, we have developed a framework and defined it. We have designed EVAD items and their complementary tool for rating adverse events. Content validation by expert judges resulted in CVR = 1.0 for each item and CVI = 0.79 in sufficiency, 0.76 in clarity, 0.91 in coherence and 0.95 in relevance for all items (p < 0.001). Final version of EVAD were applied to three participants for 7 weeks. Overall EVAD seems to be clear and meaningful for participants. CONCLUSIONS: EVAD is a semistructured interview based on a consistent conceptual framework, and proven content validity following the most important guidelines described in the literature. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03878186.

Pharmacogenetic interactions of efavirenz or rifampin and isoniazid with levonorgestrel emergency contraception during treatment of HIV or tuberculosis.

OBJECTIVE: In AIDS Clinical Trials Group study A5375, a pharmacokinetic trial of levonorgestrel emergency contraception, double-dose levonorgestrel (3 mg, versus standard dose 1.5 mg) offset the induction effects of efavirenz or rifampin on plasma levonorgestrel exposure over 8 h post-dose (AUC 0-8h ). We characterized the pharmacogenetics of these interactions. METHODS: Cisgender women receiving efavirenz- or dolutegravir-based HIV therapy, or on isoniazid-rifampin for tuberculosis, were followed after a single oral dose of levonorgestrel. Linear regression models, adjusted for BMI and age, characterized associations of CYP2B6 and NAT2 genotypes (which affect plasma efavirenz and isoniazid exposure, respectively) with levonorgestrel pharmacokinetic parameters. RESULTS: Of 118 evaluable participants, 17 received efavirenz/levonorgestrel 1.5 mg, 35 efavirenz/levonorgestrel 3 mg, 34 isoniazid-rifampin/levonorgestrel 3 mg, and 32 (control group) dolutegravir/levonorgestrel 1.5 mg. There were 73 Black and 33 Asian participants. Regardless of genotype, women on efavirenz and isoniazid-rifampin had higher levonorgestrel clearance. In the efavirenz/levonorgestrel 3 mg group, CYP2B6 normal/intermediate metabolizers had levonorgestrel AUC 0-8h values similar to controls, while CYP2B6 poor metabolizers had AUC 0-8h values of 40% lower than controls. In the isoniazid-rifampin group, NAT2 rapid/intermediate acetylators had levonorgestrel AUC 0-8h values similar to controls, while NAT2 slow acetylators had AUC 0-8h values 36% higher than controls. CONCLUSION: CYP2B6 poor metabolizer genotypes exacerbate the efavirenz-levonorgestrel interaction, likely by increased CYP3A induction with higher efavirenz exposure, making the interaction more difficult to overcome. NAT2 slow acetylator genotypes attenuate the rifampin-levonorgestrel interaction, likely by increased CYP3A inhibition with higher isoniazid exposure.

Acceptability and Feasibility of Providing Adherence Feedback Based on Tenofovir Diphosphate in Dried Blood Spots: Results from a Pilot Study Among Patients and Providers in Cape Town, South Africa.

Tenofovir diphosphate (TFV-DP) concentrations in dried blood spots (DBS) predict viral breakthrough, but their use remains understudied in real-world clinic settings. This pilot study examined acceptability, feasibility, and initial adherence outcomes of providing adherence feedback using TFV-DP concentrations on patient- and provider-levels in Cape Town, South Africa. We enrolled 60 persons with HIV (PWH) receiving tenofovir-containing ART attending a primary health clinic. They were randomized 1:1 to an intervention receiving TFV-DP concentration feedback by research staff vs. no feedback at monthly visits for 4 months. Acceptability among medical providers and level of clinical follow-up of TFV-DP results was examined. Patient acceptability was assessed descriptively. Mean electronic adherence (EA), as measured by WisePill device, and TFV-DP in DBS were compared between the two arms. All participants in the intervention group (100%) reported finding TFV-DP feedback helpful and 86% reported changing adherence behaviors. Medical providers indicated high acceptability of incorporating TFV-DP concentration feedback into the clinic, yet among 29 results < 1000 fmol/punch, only 2 were reviewed with no follow-up actions performed. In the intervention arm, mean TFV-DP concentrations were significantly higher (t = 2.5, p < .01) during follow-up and EA in upper quartile (96-100%) was greater compared to controls (x2 = 7.8, p ≤ .05). This study found high acceptability among patients for receiving adherence feedback based on TFV-DP concentrations. TFV-DP and EA data demonstrated greater adherence in the intervention group. Providers indicated high acceptability of incorporating TFV-DP feedback into the clinic, but few providers reviewed results, which could impact clinic-level feasibility.

Pyridostigmine reduces mortality of patients with severe SARS-CoV-2 infection: A phase 2/3 randomized controlled trial.

BACKGROUND: Respiratory failure in severe coronavirus disease 2019 (COVID-19) is associated with a severe inflammatory response. Acetylcholine (ACh) reduces systemic inflammation in experimental bacterial and viral infections. Pyridostigmine increases the half-life of endogenous ACh, potentially reducing systemic inflammation. We aimed to determine if pyridostigmine decreases a composite outcome of invasive mechanical ventilation (IMV) and death in adult patients with severe COVID-19. METHODS: We performed a double-blinded, placebo-controlled, phase 2/3 randomized controlled trial of oral pyridostigmine (60 mg/day) or placebo as add-on therapy in adult patients admitted due to confirmed severe COVID-19 not requiring IMV at enrollment. The primary outcome was a composite of IMV or death by day 28. Secondary outcomes included reduction of inflammatory markers and circulating cytokines, and 90-day mortality. Adverse events (AEs) related to study treatment were documented and described. RESULTS: We recruited 188 participants (94 per group); 112 (59.6%) were men; the median (IQR) age was 52 (44-64) years. The study was terminated early due to a significant reduction in the primary outcome in the treatment arm and increased difficulty with recruitment. The primary outcome occurred in 22 (23.4%) participants in the placebo group vs. 11 (11.7%) in the pyridostigmine group (hazard ratio, 0.47, 95% confidence interval 0.24-0.9; P = 0.03). This effect was driven by a reduction in mortality (19 vs. 8 deaths, respectively). CONCLUSION: Our data indicate that adding pyridostigmine to standard care reduces mortality among patients hospitalized for severe COVID-19.

Incidence of Cytomegalovirus disease and viral replication kinetics in seropositive liver transplant recipients managed under preemptive therapy in a tertiary-care center in Mexico City: a retrospective cohort study.

BACKGROUND: In the absence of an adequate prevention strategy, up to 20% of CMV IgG+ liver transplant recipients (LTR) will develop CMV disease. Despite improved reporting in CMV-DNAemia, there is no consensus as to what the ideal CMV-DNAemia cutoff for a successful preemptive strategy is. Each transplant centre establishes their own threshold. We aimed to determine the effectiveness of our preventive strategy in CMV IgG+ LTR, and evaluate CMV replication kinetics. METHODS: In this retrospective study we determined the incidence of CMV disease in the first 6 months following transplantation in CMV seropositive LTR in a tertiary-care centre in Mexico. Secondary outcomes were determining the number of patients who required preemptive therapy (treatment cutoff ≥ 4000 UI/ml), adherence to the centre's prevention protocol and calculation of viral replication kinetics. RESULTS: One-hundred and twenty-four patients met inclusion criteria. Four patients (3.2%) developed CMV disease. Ninety-six (85%) had detectable DNAemia and 25 (22%) asymptomatic patients received preemptive therapy, none of them developed CMV disease. The highest viral loads were observed on the second posttransplant month. The number of viral load measurements decreased over time. Patients with DNAemia ≥ 4000 UI/ml had a faster viral load growth rate, shorter viral load duplication time, and higher basic reproductive number. Viral load growth rate and autoimmune hepatitis were associated with development of DNAemia ≥ 4000 UI/ml. CONCLUSION: Cytomegalovirus disease occurred in 3.2% of the study subjects. Preemptive therapy using a threshold of CMV ≥ 4000 UI/ml was effective in reducing the incidence of end-organ disease. The viral replication parameters described in this population highlight the importance of frequent monitoring, a challenging feat for transplant programs in low- and middle-income countries.

Guillain-Barré syndrome outbreak in Tapachula temporally associated with the Zika virus introduction in Southern Mexico.

The Guillain-Barré syndrome (GBS) has been previously associated with Zika virus infection. We analysed the data from all the patients with GBS diagnosis that were admitted to a referral hospital, in Tapachula City during the period from January 2013 to August 2016, comparing the incidence of GBS according to the temporality of the Zika outbreak in Southern Mexico. Additionally, we described the clinical and epidemiological characteristics of the GBS patients admitted before or after the Zika outbreak. We observed a sharp increase in the number of patients hospitalised due to GBS from the time the first confirmed Zika cases appeared in Mexico. Clinically we observed GBS cases before zika outbreak had more frequently history of respiratory/gastrointestinal symptoms and GBS during zika outbreak had significantly more frequently recent history of rash/conjunctivitis. Although we cannot affirm that the increased cases of GBS have a specific aetiologic association with Zika, our results suggest that this observed outbreak of in Tapachula, might have been associated to the emerging Zika epidemic, locally and suggests that rare complications associated with acute infections (such as GBS) might be useful in the surveillance systems for emerging infections.

Result Turnaround Time of RT-PCR for SARS-CoV-2 is the Main Cause of COVID-19 Diagnostic Delay: A Country-Wide Observational Study of Mexico and Colombia.

BACKGROUND: Delay in COVID-19 diagnosis due to late real-time reverse transcription-polymerase chain reaction reporting has been described to be an important cause of suboptimal COVID-19 surveillance and outbreak containment. OBJECTIVE: The objective of the study was to determine the duration of diagnostic delay due to test turnaround time and its association with marginalization status. METHODS: In this observational study using national open data of Mexico and Colombia, we quantified the delay in COVID-19 diagnosis that occurred in both countries. We considered two periods that contributed to the delay in diagnosis: the time from symptom onset until testing (delay-one) and test turnaround time (delay-two). Marginalization status was determined according to country-specific scores. RESULTS: Among 3,696,773 patients from Mexico and Colombia, delay-two was generally longer than delay-one. Median delay-one was 3 days and delay-two 7 days in Colombia, while in Mexico, they were 3 days and 4 days, respectively. In Colombia, worse marginalization status prolonged delaytwo. In Mexico, a lower number and percentage of rapid tests were performed in areas with worse marginalization. CONCLUSION: Diagnostic delay was mostly due to test turnaround time. Marginalization status was an important barrier to diagnostic test access.

Different epidemiological profiles in patients with Zika and dengue infection in Tapachula, Chiapas in Mexico (2016-2018): an observational, prospective cohort study.

BACKGROUND: The introduction of Zika and chikungunya to dengue hyperendemic regions increased interest in better understanding characteristics of these infections. We conducted a cohort study in Mexico to evaluate the natural history of Zika infection. We describe here the frequency of Zika, chikungunya and dengue virus infections immediately after Zika introduction in Mexico, and baseline characteristics of participants for each type of infection. METHODS: Prospective, observational cohort evaluating the natural history of Zika virus infection in the Mexico-Guatemala border area. Patients with fever, rash or both, meeting the modified criteria of PAHO for probable Zika cases were enrolled (June 2016-July 2018) and followed-up for 6 months. We collected data on sociodemographic, environmental exposure, clinical and laboratory characteristics. Diagnosis was established based on viral RNA identification in serum and urine samples using RT-PCR for Zika, chikungunya, and dengue. We describe the baseline sociodemographic and environmental exposure characteristics of participants according to diagnosis, and the frequency of these infections over a two-year period immediately after Zika introduction in Mexico. RESULTS: We enrolled 427 participants. Most patients (n = 307, 65.7%) had an acute illness episode with no identified pathogen (UIE), 37 (8%) Zika, 82 (17.6%) dengue, and 1 (0.2%) chikungunya. In 2016 Zika predominated, declined in 2017 and disappeared in 2018; while dengue increased after 2017. Patients with dengue were more likely to be men, younger, and with lower education than those with Zika and UIE. They also reported closer contact with water sources, and with other people diagnosed with dengue. Participants with Zika reported sexual exposure more frequently than people with dengue and UIE. Zika was more likely to be identified in urine while dengue was more likely found in blood in the first seven days of symptoms; but PCR results for both were similar at day 7-14 after symptom onset. CONCLUSIONS: During the first 2 years of Zika introduction to this dengue hyper-endemic region, frequency of Zika peaked and fell over a two-year period; while dengue progressively increased with a predominance in 2018. Different epidemiologic patterns between Zika, dengue and UIE were observed. Trial registration Clinical.Trials.gov (NCT02831699).

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.

A parallel-group, multicenter randomized, double-blinded, placebo-controlled, phase 2/3, clinical trial to test the efficacy of pyridostigmine bromide at low doses to reduce mortality or invasive mechanical ventilation in adults with severe SARS-CoV-2 infection: the Pyridostigmine In Severe COvid-19 (PISCO) trial protocol.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the causative agent of coronavirus disease 2019 (COVID-19), may lead to severe systemic inflammatory response, pulmonary damage, and even acute respiratory distress syndrome (ARDS). This in turn may result in respiratory failure and in death. Experimentally, acetylcholine (ACh) modulates the acute inflammatory response, a neuro-immune mechanism known as the inflammatory reflex. Recent clinical evidence suggest that electrical and chemical stimulation of the inflammatory reflex may reduce the burden of inflammation in chronic inflammatory diseases. Pyridostigmine (PDG), an ACh-esterase inhibitor (i-ACh-e), increases the half-life of endogenous ACh, therefore mimicking the inflammatory reflex. This clinical trial is aimed at evaluating if add-on of PDG leads to a decrease of invasive mechanical ventilation and death among patients with severe COVID-19. METHODS: A parallel-group, multicenter, randomized, double-blinded, placebo-controlled, phase 2/3 clinical trial to test the efficacy of pyridostigmine bromide 60 mg/day P.O. to reduce the need for invasive mechanical ventilation and mortality in hospitalized patients with severe COVID-19. DISCUSSION: This study will provide preliminary evidence of whether or not -by decreasing systemic inflammation- add-on PDG can improve clinical outcomes in patients with severe COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04343963 (registered on April 14, 2020).

Impact of RT-PCR Test False-Negative Results for SARS-CoV-2 Surveillance in Mexico.

Background: Underestimation of the number of cases during the coronavirus disease 2019 (COVID-19) pandemic has been a constant concern worldwide. Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA using realtime reverse-transcription polymerase chain reaction (RT-PCR) is the most common method to confirm a case. However, these tests have suboptimal sensitivity. Objective: The objective of the study was to estimate the number of COVID-19 confirmed cases, intensive care unit (ICU) admissions and deaths in Mexico, accounting for the probabilities of false-negative tests. Methods: We used publicly available, national databases of all SARS-CoV-2 tests performed at public laboratories in Mexico between February 27 and October 31, 2020. We used the estimated probabilities of false-negative tests based on the day of clinical sample collection after symptom initiation calculated previously. With the resulting model, we estimated the corrected daily number of cases, ICU admissions, and deaths. Results: Among 2,024,822 people tested in Mexico between February 27 and October 31 with an available result, we estimated 1,248,583 (95% confidence interval 1,094,850-1,572,818) cases, compared to 902,343 cases reported with positive tests. ICU admissions and deaths were 15% and 8% higher than reported, respectively. Conclusion: Accounting for SARS-CoV-2 RT-PCR-based diagnostic tests' precision is a simple way to improve estimations for the true number of COVID-19 cases among tested persons.

Progressive disseminated histoplasmosis in Latin America and the Caribbean in people receiving highly active antiretroviral therapy for HIV infection: A systematic review.

Histoplasmosis is the most clinically significant mycosis in Latin America; still it has been neglected in people with human immunodeficiency virus (HIV). There is limited information about its contribution to morbidity and mortality in this population. We conducted a systematic review of scientific literature to provide an estimation of the frequency and mortality of histoplasmosis among people with HIV receiving highly active antiretroviral therapy (HAART) in Latin America, and factors associated with mortality. We searched articles in PubMed, Scopus, WHO Global health library, and Scielo using different combination of terms including "histoplasmosis" and HAART. We identified 949 articles, removed 662 duplicated; screened 287 abstracts; reviewed full text of 53 articles; and selected 15 articles that provided information on the number of patients studied, included patients receiving ART, and reported any measure of frequency estimate for qualitative synthesis. Studies were conducted in Argentina (n = 4), Brazil (n = 6), Colombia (n = 2), French Guyana and the Bahamas (=2), and Guatemala (n = 1). Heterogeneity of studies characteristics precluded any aggregated estimates. Histoplamosis was frequent in these cohort studies and mortality was high despite the use of HAART. Low CD4 counts, delayed HAART initiation and poor adherence were related to increased incidence, poor prognosis and increased mortality, respectively. Histoplasmosis may be an important contributor to mortality in people with HIV in Latin America. Diagnostic delays represent an important limitation for improving care of patients suspected to have histoplasmosis. Reducing histoplasmosis diagnostic delays and therapy initiation is needed to further decrease mortality.

Correlates of depressive symptoms among older adults living with HIV.

OBJECTIVE: To establish the correlates of depressive symptoms among Mexican community-dwelling older people living with HIV (PLWHIV). METHODS: Cross-sectional, 2-center study of 328 participants aged 50 or older being followed in the outpatient HIV clinics of 2 tertiary care hospitals in Mexico. Data were obtained through a comprehensive geriatric assessment. Multivariate logistic regression analyses were performed to identify the correlates of depressive symptoms. RESULTS: Mean age of participants was 58.4 years (SD = 7.2), and 82.9% were men. Depressive symptoms were present in 15.9% of participants. The multivariate logistic regression models showed that frailty and disability for activities of daily living were both independently associated with depressive symptoms. CONCLUSION: Frailty and disability were independent correlates of depressive symptoms in older PLWHIV. Future studies should attempt to explore the role of physical frailty and disability on psychosocial morbidity among older PLWHIV.

Substance Use and Adherence Among People Living with HIV/AIDS Receiving cART in Latin America.

This cross-sectional study describes substance use prevalence and its association with combination antiretroviral therapy (cART) adherence among 3343 individuals receiving care at HIV clinics in Argentina, Brazil, Chile, Honduras, Mexico, and Peru. A rapid screening tool evaluated self-reported 7-day recall of alcohol, marijuana, cocaine, heroin, and methamphetamine use, and missed cART doses. Overall, 29.3 % individuals reported having ≥1 alcoholic drinks, 5.0 % reported any illicit drug use and 17.0 % reported missed cART doses. In the logistic regression model, compared to no substance use, alcohol use [adjusted odds ratio (AOR) = 2.46, 95 % confidence interval (CI): 1.99-3.05], illicit drug use (AOR = 3.57, 95 % CI: 2.02-6.30), and using both alcohol and illicit drugs (AOR = 4.98, 95 % CI: 3.19-7.79) were associated with missed cART doses. The associations between substance use and likelihood of missing cART doses point to the need of targeting alcohol and illicit drug use to improve adherence among people living with HIV in Latin America.

Monitoring of HIV treatment in seven countries in the WHO Region of the Americas.

OBJECTIVE: To determine the prevalence of adequate monitoring and the costs of measuring CD4+ T-lymphocytes (CD4+ cell) and human immunodeficiency virus (HIV) viral load in people receiving antiretroviral therapy (ART) in seven countries in the WHO Region of the Americas. METHODS: We obtained retrospective, longitudinal data for 14 476 adults who started a first ART regimen at seven HIV clinics in Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru between 2000 and 2011. We estimated the proportion of 180-day periods with adequate monitoring, which we defined as at least one CD4+ cell count and one viral load measurement. Factors associated with adequate monitoring were analysed using regression methods. The costs of the tests were estimated. FINDINGS: The median follow-up time was 50.4 months; the proportion of 180-day periods with adequate CD4+ cell counts was 69% while the proportion with adequate monitoring was 62%. Adequate monitoring was more likely in participants who were older, who started ART more recently, whose first regimen included a non-nucleoside reverse transcriptase inhibitor or who had a CD4+ cell count less than 200 cells/µl at ART initiation. The cost of one CD4+ cell count ranged from 7.37 United States dollars (US$) in Argentina to US$ 64.09 in Chile; the cost of one viral load measurement ranged from US$ 20.34 in Brazil to US$ 186.28 in Haiti. CONCLUSION: In HIV-infected participants receiving ART in the WHO Region of the Americas, CD4+ cell count and viral load monitoring was often carried out less frequently than regional guidelines recommend. The laboratory costs of monitoring varied greatly.

Surveillance of Oseltamivir-Resistant Influenza A(H1N1)pdm09 in Guanajuato State, Mexico from 2009 to 2012.

BACKGROUND: The influenza A(H1N1)pdm09 virus was first identified in Mexico in April 2009, subsequently spreading worldwide. Soon after the WHO declared a pandemic, a series of cases involving oseltamivir-resistant viruses were described, following concerns about the spread of strains resistant to neuraminidase inhibitors that could hamper control measures. To study the prevalence of oseltamivir-resistant influenza A(H1N1)pdm09, we implemented a surveillance program across the state of Guanajuato, Mexico. METHODS: We collected respiratory samples from patients with confirmed infection with influenza A(H1N1)pdm09 virus between 2009 and 2012 in rural and urban regions in Guanajuato, Mexico. Specimens were screened for the H275Y mutation by Sanger sequencing. RESULTS: A total of 1,192 laboratory confirmed influenza A(H1N1)pdm09-positive samples were processed between 2009 and 2012. Using two endpoint real-time polymerase chain reaction, 575 samples were sequenced. Two different clusters, I and II, were identified. The H275Y substitution was found in only one sample from cluster I. CONCLUSIONS: The prevalence of oseltamivir-resistant influenza A(H1N1)pdm09 2009 viruses during the pandemic period and following years was very low in our State.

The impact of earthquakes in Latin America on the continuity of HIV care: A retrospective observational cohort study.

Objectives: As earthquakes occur frequently in Latin America and can cause significant disruptions in HIV care, we sought to analyze patterns of HIV care for adults at Latin American clinical sites experiencing a significant earthquake within the past two decades. Study design: Retrospective clinical cohort study. Methods: Adults receiving HIV care at sites experiencing at least a "moderate intensity" (Modified Mercalli scale) earthquake in the Caribbean, Central and South America network for HIV epidemiology (CCASAnet) contributed data from 2003 to 2017. Interrupted Time Series models were fit with discontinuities at site-specific earthquake dates (Sept. 16, 2015 in Chile; Apr. 18, 2014 and Sept. 19, 2017 in Mexico; and Aug. 15, 2007 in Peru) to assess clinical visit, CD4 measure, viral load lab, and ART initiation rates 3- and 6-months after versus before earthquakes. Results: Comparing post-to pre-earthquake periods, there was a sharp drop in median visit (incidence rate ratio [IRR] = 0.79, 95% confidence interval [CI]: 0.68-0.91) and viral load lab (IRR = 0.78, 95% CI: 0.62-0.99) rates per week, using a 3-month window. CD4 measurement rates also decreased (IRR = 0.43; 95% CI: 0.37-0.51), though only using a 6-month window. Conclusions: Given that earthquakes occur frequently in Latin America, disaster preparedness plans must be more broadly implemented to avoid disruptions in HIV care and attendant poor outcomes.