Hospital admissions and mortality for acute exacerbations of COPD during the COVID-19 pandemic: A nationwide study in France.

Background: A global reduction in hospital admissions for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) was observed during the first months of the COVID-19 pandemic. Large-scale studies covering the entire pandemic period are lacking. We investigated hospitalizations for AECOPD and the associated in-hospital mortality at the national level in France during the first 2 years of the pandemic. Methods: We used the French National Hospital Database to analyse the time trends in (1) monthly incidences of hospitalizations for AECOPD, considering intensive care unit (ICU) admission and COVID-19 diagnoses, and (2) the related in-hospital mortality, from January 2016 to November 2021. Pandemic years were compared with the pre-pandemic years using Poisson regressions. Results: The database included 565,890 hospitalizations for AECOPD during the study period. The median age at admission was 74 years (interquartile range 65-83), and 37% of the stays concerned women. We found: (1) a dramatic and sustainable decline in hospitalizations for AECOPD over the pandemic period (from 8,899 to 6,032 monthly admissions, relative risk (RR) 0.65, 95% confidence interval (CI) 0.65-0.66), and (2) a concomitant increase in in-hospital mortality for AECOPD stays (from 6.2 to 7.6% per month, RR 1.24, 95% CI 1.21-1.27). The proportion of stays yielding ICU admission was similar in the pre-pandemic and pandemic years, 21.5 and 21.3%, respectively. In-hospital mortality increased to a greater extent for stays without ICU admission (RR 1.39, 95% CI 1.35-1.43) than for those with ICU admission (RR 1.09, 95% CI 1.05-1.13). Since January 2020, only 1.5% of stays were associated with a diagnosis of COVID-19, and their mortality rate was nearly three-times higher than those without COVID-19 (RR 2.66, 95% CI 2.41-2.93). Conclusion: The decline in admissions for AECOPD during the pandemic could be attributed to a decrease in the incidence of exacerbations for COPD patients and/or to a possible shift from hospital to community care. The rise in in-hospital mortality is partially explained by COVID-19, and could be related to restricted access to ICUs for some patients and/or to greater proportions of severe cases among the patients hospitalized during the pandemic.

Prevalence of High-Risk Human Papillomavirus Infections before and after Cervical Lesion Treatment, among Women Living with HIV.

Even when receiving combination antiretroviral therapy, women living with HIV are at high risk of human papillomavirus (HPV) infection and/or cervical lesions, including cancer. Using data from the PapilloV prospective cohort, we evaluated the prevalence of high-risk HPV (HR-HPV) infections after cervical lesion treatment and investigated factors associated with their carriage. Women were followed up for three years with annual Pap smear and HPV genotyping. We offered treatment to women presenting either a Pap smear with high-grade squamous intraepithelial lesion or higher, and/or a biopsy showing cervical intraepithelial neoplasia II or III. We compared the prevalence of HR-HPV infection at the time of first treatment indication and at the end of follow-up among women who received treatment and those who did not. Overall, 46 women had treatment indication. HR-HPV prevalence significantly decreased from 67% to 27% (p value = 0.001) in the 30 women who received treatment, while it did not significantly decrease (from 56% to 38%) in the 16 women who did not (p value = 0.257). Due to lack of statistical power, the 40% relative difference in HR-HPV carriage between treated and untreated women was not significant. In women living with HIV, the treatment of a cervical lesion may be beneficial for clearing HR-HPV infections.

School trajectory disruption among adolescents living with perinatal HIV receiving antiretroviral treatments: a case-control study in Thailand.

BACKGROUND: Adolescents living with perinatal HIV often experience difficult living circumstances that can impact educational achievement and thus their transition to adult life. We explored their school trajectories and evaluated the contribution of perinatal HIV-infection, in Thailand, where education is free and compulsory until the age of 15. METHODS: We used data from the Teens Living with Antiretrovirals (TEEWA) study, a cross-sectional case-control study conducted from 2011 to 2014 in Thailand. Participants were 707 adolescents living with perinatal HIV (ALPHIV, cases) aged 12-19 receiving antiretroviral therapy in 19 hospitals throughout Thailand and 689 HIV-uninfected adolescents (controls) living in the same institutions or, for those living in family settings, randomly selected from the general population and individually matched for sex, age, and place of residence. School trajectory disruption was defined as ≥1 year of academic delay or as early school dropout (before 15 years of age). Logistic regression models were used to assess factors independently associated with disrupted school trajectory and to estimate the proportion of school disruption attributable to HIV-infection. We used multivariate imputations by chained equations (MICE) to manage missing data and performed two sensitivity analyses to evaluate the main model's reliability. RESULTS: The study population's median age was 14.5 years (58% female). School trajectory disruption was experienced by 37% of ALPHIV and 12% of the controls. After adjusting for sociodemographic factors, ALPHIV were 5 times more likely to experience disruption than controls (ORA =5.2 [3.7-7.2]). About 50% of school trajectory disruption was attributable to HIV-infection. Males and adolescents living in institutions were more likely to experience school trajectory disruption (ORA =1.8 [1.3-2.4] and ORA =11.0 [7.7-15.8], respectively). Among ALPHIV, neurocognitive difficulties and growth delay were significantly associated with disruption (ORA =3.3 [2.1-5.2] and ORA =1.8 [1.3-2.6], respectively). For those living in families, disruption was also associated with having a caregiver who had less than a secondary-level education (ORA =2.1 [1.1-3.9]) or having experienced stigmatization (ORA =1.9 [1.2-3.1]). CONCLUSIONS: HIV and contextual factors combine to aggravate the educational disadvantage among ALPHIV. The impact of this disadvantage on their life prospects, especially regarding access to higher education and professional achievement, should be further explored.

Incidence of Tuberculosis and Associated Mortality in a Cohort of Human Immunodeficiency Virus-Infected Children Initiating Antiretroviral Therapy.

BACKGROUND.: We assessed the incidence of tuberculosis, risk factors for tuberculosis, and the contribution of tuberculosis on mortality in a large cohort of human immunodeficiency virus (HIV)-infected children <15 years of age initiating first-line antiretroviral therapy (ART) between 1999 and 2012 in Thailand, one of the 22 high tuberculosis burden countries. METHODS.: A physician reviewed and classified tuberculosis cases. Incidence was the number of children with incident tuberculosis, defined as a first or recurrent tuberculosis diagnosis >30 days after ART initiation, divided by the total person-years of follow-up (PYFU). Risk factors for incident tuberculosis were identified using Fine and Gray's competing risks models, with death from other causes treated as a competing event, and risk factors for death were identified using Cox models. RESULTS.: At ART initiation, 670 children (55% female) had a median age of 6.4 years (interquartile range, 2.0-9.6), body mass index-for-age z-score -0.8 (-1.9 to 0.0), HIV ribonucleic acid viral load 5.1 log10 copies/mL (4.6-5.6), and CD4 9% (3-17). Median duration of follow-up was 7.7 years. Tuberculosis incidence was 7 per 1000 PYFU (95% confidence interval [CI], 5-11) and decreased with ART duration. Lower age-adjusted hemoglobin, hematocrit, and CD4 at ART initiation were associated with a higher risk of incident tuberculosis. Of the 30 incident tuberculosis cases, 9 died. Diagnosis of incident tuberculosis was associated with mortality (unadjusted hazard ratio = 10.2, 95% CI = 4.8-21.5, P < .001 and adjusted hazard ratio = 5.4, 95% CI = 2.5-11.7, P < .001). CONCLUSIONS.: Incident tuberculosis was strongly associated with mortality. CD4 counts or hemoglobin or hematocrit levels may prompt clinicians to consider a possible tuberculosis infection.

HIV-related stigma experiences: Understanding gender disparities in Thailand.

This paper assesses the relationship between gender and HIV-related stigma experiences among people living with HIV (PLHIV) - enacted and anticipated stigma - and PLHIV caregivers - courtesy stigma - in Northern Thailand, along with the underlying reasons for stigmatising attitudes towards PLHIV - instrumental and symbolic stigma - expressed in the general population. We used data from the Living With Antiretrovirals (LIWA) study conducted on all PLHIV receiving antiretroviral treatment in four district hospitals in Northern Thailand (n = 513) and on a community sample of adults from the general population (n = 500). Women living with HIV and female caregivers of PLHIV reported higher rates of HIV-related stigma experiences than men. Gender interacted with other predictors - the period of HIV diagnosis and age - to increase the level of stigma experienced. Among the general population, attitudes of contact avoidance were infrequent. However, stereotypes depicting PLHIV as blameworthy were highly pervasive, with women perceived as the "victims" of their spouse's irresponsible sexual behaviours. In this context, women were yet more often subjected to HIV-related stigma than men, in particular women diagnosed in the pre-antiretroviral therapy era and younger female caregivers. The role of gender in shaping disparities in HIV-related stigma experiences is discussed.

New-Onset Diabetes and Antiretroviral Treatments in HIV-Infected Adults in Thailand.

BACKGROUND: Use of several antiretrovirals (ARVs) has been shown to be associated with a higher risk of diabetes in HIV-infected adults. We estimated the incidence of new-onset diabetes and assessed the association between individual ARVs and ARV combinations, and diabetes in a large cohort in Thailand. METHODS: We selected all HIV-1-infected, nondiabetic, antiretroviral-naive adults enrolled in the Program for HIV Prevention and Treatment cohort (NCT00433030) between January 2000 and December 2011. Diabetes was defined as confirmed fasting plasma glucose ≥ 126 mg/dL or random plasma glucose ≥ 2 00 mg/dL. Incidence was the number of cases divided by the total number of person-years of follow-up. Association between ARVs and ARV combinations, and new-onset diabetes was assessed using Cox proportional hazards models. RESULTS: Overall, 1594 HIV-infected patients (76% female) were included. Median age at antiretroviral therapy initiation was 32.5 years. The incidence rate of diabetes was 5.0 per 1000 person-years of follow-up (95% confidence interval: 3.8 to 6.6) (53 cases). In analyses adjusted for potential confounders, exposure to stavudine + didanosine [adjusted hazard ratio (aHR) = 3.9; P = 0.001] and cumulative exposure ≥ 1 year to zidovudine (aHR = 2.3 vs. no exposure; P = 0.009) were associated with a higher risk of diabetes. Conversely, cumulative exposure ≥ 1 year to tenofovir (aHR = 0.4 vs. no exposure; P = 0.02) and emtricitabine (aHR = 0.4 vs. no exposure; P = 0.03) were associated with a lower risk. CONCLUSIONS: The incidence of diabetes in this predominantly female, young, lean population was relatively low. Although stavudine and didanosine have now been phased out in most antiretroviral therapy programs, our analysis suggests a higher risk of diabetes with zidovudine, frequently prescribed today in resource-limited settings.

Treatment Failure in HIV-Infected Children on Second-line Protease Inhibitor-Based Antiretroviral Therapy.

BACKGROUND: Human immunodeficiency virus (HIV)-infected children failing second-line antiretroviral therapy (ART) have no access to third-line antiretroviral drugs in many resource-limited settings. It is important to identify risk factors for second-line regimen failure. METHODS: HIV-infected children initiating protease inhibitor (PI)-containing second-line ART within the Program for HIV Prevention and Treatment observational cohort study in Thailand between 2002 and 2010 were included. Treatment failure was defined as confirmed HIV type 1 RNA load >400 copies/mL after at least 6 months on second-line regimen or death. Adherence was assessed by drug plasma levels and patient self-report. Cox proportional hazards regression analyses were used to identify risk factors for failure. RESULTS: A total of 111 children started a PI-based second-line regimen, including 59 girls (53%). Median first-line ART duration was 1.9 years (interquartile range [IQR], 1.4-3.3 years), and median age at second-line initiation was 10.7 years (IQR, 6.3-13.4 years). Fifty-four children (49%) experienced virologic failure, and 2 (2%) died. The risk of treatment failure 24 months after second-line initiation was 41%. In multivariate analyses, failure was independently associated with exposure to first-line ART for >2 years (adjusted hazard ratio [aHR], 1.8; P = .03), age >13 years (aHR, 2.9; P < .001), body mass index-for-age z score < -2 standard deviations at second-line initiation (aHR, 2.8; P = .03), and undetectable drug levels within 6 months following second-line initiation (aHR, 4.5; P < .001). CONCLUSIONS: Children with longer exposure to first-line ART, entry to adolescence, underweight, and/or undetectable drug levels were at higher risk of failing second-line ART and thus should be closely monitored.

Switching HIV treatment in adults based on CD4 count versus viral load monitoring: a randomized, non-inferiority trial in Thailand.

BACKGROUND: Viral load (VL) is recommended for monitoring the response to highly active antiretroviral therapy (HAART) but is not routinely available in most low- and middle-income countries. The purpose of the study was to determine whether a CD4-based monitoring and switching strategy would provide a similar clinical outcome compared to the standard VL-based strategy in Thailand. METHODS AND FINDINGS: The Programs for HIV Prevention and Treatment (PHPT-3) non-inferiority randomized clinical trial compared a treatment switching strategy based on CD4-only (CD4) monitoring versus viral-load (VL). Consenting participants were antiretroviral-naïve HIV-infected adults (CD4 count 50-250/mm(3)) initiating non-nucleotide reverse transcriptase inhibitor (NNRTI)-based therapy. Randomization, stratified by site (21 public hospitals), was performed centrally after enrollment. Clinicians were unaware of the VL values of patients randomized to the CD4 arm. Participants switched to second-line combination with confirmed CD4 decline >30% from peak (within 200 cells from baseline) in the CD4 arm, or confirmed VL >400 copies/ml in the VL arm. Primary endpoint was clinical failure at 3 years, defined as death, new AIDS-defining event, or CD4 <50 cells/mm(3). The 3-year Kaplan-Meier cumulative risks of clinical failure were compared for non-inferiority with a margin of 7.4%. In the intent to treat analysis, data were censored at the date of death or at last visit. The secondary endpoints were difference in future-drug-option (FDO) score, a measure of resistance profiles, virologic and immunologic responses, and the safety and tolerance of HAART. 716 participants were randomized, 356 to VL monitoring and 360 to CD4 monitoring. At 3 years, 319 participants (90%) in VL and 326 (91%) in CD4 were alive and on follow-up. The cumulative risk of clinical failure was 8.0% (95% CI 5.6-11.4) in VL versus 7.4% (5.1-10.7) in CD4, and the upper-limit of the one-sided 95% CI of the difference was 3.4%, meeting the pre-determined non-inferiority criterion. Probability of switch for study criteria was 5.2% (3.2-8.4) in VL versus 7.5% (5.0-11.1) in CD4 (p=0.097). Median time from treatment initiation to switch was 11.7 months (7.7-19.4) in VL and 24.7 months (15.9-35.0) in CD4 (p=0.001). The median duration of viremia >400 copies/ml at switch was 7.2 months (5.8-8.0) in VL versus 15.8 months (8.5-20.4) in CD4 (p=0.002). FDO scores were not significantly different at time of switch. No adverse events related to the monitoring strategy were reported. CONCLUSIONS: The 3-year rates of clinical failure and loss of treatment options did not differ between strategies although the longer-term consequences of CD4 monitoring would need to be investigated. These results provide reassurance to treatment programs currently based on CD4 monitoring as VL measurement becomes more affordable and feasible in resource-limited settings. TRIAL REGISTRATION: ClinicalTrials.govNCT00162682 Please see later in the article for the Editors' Summary.

Laboratory and clinical predictors of disease progression following initiation of combination therapy in HIV-infected adults in Thailand.

BACKGROUND: Data on determinants of long-term disease progression in HIV-infected patients on antiretroviral therapy (ART) are limited in low and middle-income settings. METHODS: Effects of current CD4 count, viral load and haemoglobin and diagnosis of AIDS-defining events (ADEs) after start of combination ART (cART) on death and new ADEs were assessed using Poisson regression, in patient aged ≥ 18 years within a multi-centre cohort in Thailand. RESULTS: Among 1,572 patients, median follow-up from cART initiation was 4.4 (IQR 3.6-6.3) years. The analysis of death was based on 60 events during 6,573 person-years; 30/50 (60%) deaths with underlying cause ascertained were attributable to infections. Analysis of new ADE included 192 events during 5,865 person-years; TB and Pneumocystis jiroveci pneumonia were the most commonly presented first new ADE (35% and 20% of cases, respectively). In multivariable analyses, low current CD4 count after starting cART was the strongest predictor of death and of new ADE. Even at CD4 above 200 cells/mm(3), survival improved steadily with CD4, with mortality rare at ≥ 500 cells/mm(3) (rate 1.1 per 1,000 person-years). Haemoglobin had a strong independent effect, while viral load was weakly predictive with poorer prognosis only observed at ≥ 100,000 copies/ml. Mortality risk increased following diagnosis of ADEs during cART. The decline in mortality rate with duration on cART (from 21.3 per 1,000 person-years within first 6 months to 4.7 per 1,000 person-years at ≥ 36 months) was accounted for by current CD4 count. CONCLUSIONS: Patients with low CD4 count or haemoglobin require more intensive diagnostic and treatment of underlying causes. Maintaining CD4 ≥ 500 cells/mm(3) minimizes mortality. However, patient monitoring could potentially be relaxed at high CD4 count if resources are limited. Optimal ART monitoring strategies in low-income settings remain a research priority. Better understanding of the aetiology of anaemia in patients on ART could guide prevention and treatment.