La dermatite atopique (DA) est une dermatose inflammatoire chronique caractérisée par un prurit intense. Les symptômes de la DA peuvent être invalidants et entraîner un trouble du sommeil et un retentissement psychosocial, diminuant la qualité de vie du patient. L’upadacitinib (UPA) est un inhibiteur sélectif de Janus kinase (JAK) par voie orale avec un puissance inhibitrice plus élevée pour JAK1 versus JAK2, JAK3 et tyrosine kinase 2. Les résultats d’une étude de phase 3b (Heads Up ; NCT03738397) ont démontré qu’UPA 30 mg était plus efficace que le dupilumab (DUPI) sur la réponse EASI 75 à la semaine 16. Dans cette analyse post-hoc, a été étudié le nombre de jours de maintien de la réponse EASI sous UPA ou DUPI aux semaines 16 et 24. L’étude Heads Up était une étude comparative directe multicentrique, randomisée, en double aveugle et double placebo contrôlée versus comparateur actif de 24 semaines et comparant la tolérance et l’efficacité d’UPA 30 mg à DUPI 300 mg chez les adultes atteints de DA modérée à sévère. Les patients ont été randomisés selon un ratio 1/1 pour recevoir UPA 30 mg par voie orale une fois par jour ou DUPI 300 mg par voie sous-cutanée toutes les 2 semaines après une première injection de 600 mg. L’étude a évalué la proportion moyenne de jours pendant lesquels les patients obtenaient une amélioration du score EASI de ≥ 75 %, ≥ 90 % et 100 % (EASI 75, EASI 90, EASI 100) comparativement au score à l’inclusion. Les 692 patients étaient randomisés en deux groupes : les patients traités par UPA (n = 348) ou DUPI (n = 344). À 16 et 24 semaines, une proportion plus importante de patients traités par UPA versus DUPI ont atteint une réponse EASI 100, EASI 90 et EASI 75. Au bout de 16 et 24 semaines, la proportion de jours pendant lesquels les patients étaient répondeurs EASI 100, EASI 90 et EASI 75 était supérieure pour les patients traités par UPA par rapport à DUPI. Sur 24 semaines, UPA 30 mg a permis d’obtenir une proportion plus importante de jours pendant lesquels les patients atteints de DA modérée à sévère étaient répondeurs EASI 75, EASI 90 et EASI 100 par rapport à DUPI.

BACKGROUND:Research examining associations between the clinician-reported validated Investigator Global Assessment for AD (vIGA-AD) and patient-reported disease burden is sparse. This study aims to evaluate the relationship between vIGA-AD with patient-reported disease severity and quality of life (QoL).METHODS:A cross-sectional analysis was conducted using a September 2021 data cut from the TARGET-DERM AD study, a real-world, longitudinal cohort of children, adolescents, and adults with AD enrolled at 44 academic and community dermatology and allergy sites in the US. Clinical AD severity was measured using vIGA-AD while disease severity and QoL were assessed by the Patient Oriented Eczema Measure (POEM) and (Children’s) Dermatology Life Quality Index (C/DLQI), respectively. Patient characteristics, clinical- and patient reported-outcomes were assessed by stratified POEM and C/DLQI categories using descriptive statistics. Associations with vIGA-AD were evaluated using unadjusted and adjusted ordinal logistic regression and linear regression models.RESULTS:The analysis cohort (n=1,888) primarily consisted of adults (57%), females (56%), and patients with private insurance (63%). Unadjusted analyses suggest that clinical AD severity was associated with age, with more adolescents and adults having moderate/severe vIGA-AD than pediatric patients. Clinical AD severity was also associated with disease severity, with greater POEM scores observed at greater vIGA-AD severity levels (r = 0.496 and 0.45 for adults and pediatrics, respectively). Clinical AD severity and QoL were positively correlated, with greater CDLQI/DLQI scores at greater vIGA-AD severity levels (r = 0.458 and 0.334 for DLQI and CDLQI, respectively). After adjusting for demographics and other risk factors, vIGA-AD continued to show significant associations with POEM and DLQI/CDLQI. Compared to patients with clear/almost clear disease, adults and pediatrics with moderate-to-severe AD were 8.19 and 5.78 times as likely to be in a more severe POEM category, respectively. Similarly, compared to patients with clear/almost clear disease, adults and pediatrics with moderate/severe AD were 6.69 and 3.74 times as likely to be in a more severe DLQI/CDLQI category. Adjusted linear regression analyses of DLQI in adults showed significant differences by vIGA-AD level, with mild AD and moderate/severe AD associated with a 2.26-point and 5.42-point greater DLQI relative to clear/almost clear AD.CONCLUSIONS:In this real-world study of patients with AD, greater clinician-reported disease severity is positively correlated with higher patient-reported disease severity and lower QoL. J Drugs Dermatol. 2023;22(4): doi:10.36849/JDD.7473 Access Supplementary Material here Citation: Guttman-Yassky E, Bar J, Rothenberg Lausell C, et al. Do atopic dermatitis patient-reported outcomes correlate with validated investigator global assessment? Insights from TARGET-AD registry. J Drugs Dermatol. 2023;22(4):344-355. doi:10.36849/JDD.7473.

IMPORTANCE Primary results from the Measure Up 1 and Measure Up 2 studies demonstrated upadacitinib efficacy and safety through 16 weeks in patients with atopic dermatitis. Longer-term outcomes remain unknown. OBJECTIVE To evaluate long-term (52 weeks) efficacy and safety of upadacitinib treatment in patients with atopic dermatitis. DESIGN, SETTING, AND PARTICIPANTS Measure Up 1 and Measure Up 2 are ongoing double-blind, placebo-controlled, replicate phase 3 randomized clinical trials that indude adults and adolescents with moderate to severe atopic dermatitis at Eland 154 centers, respectively. Cutoffs for this analysis were December 21, 2020 (Measure Up 1), and January 15, 2021 (Measure Up 2). INTERVENTIONS Patients were randomized 1:1:1 to receive once-daily oral upadacitinib 15 mg, 30 mg, or placebo. At week 16, patients randomized at baseline to receive upadacitinib 15 mg (273 and 260 patients in Measure Up 1 and Measure Up 2, respectively) and 30 mg (270 and 268 patients) continued assigned treatment; placebo-treated patients were rerandomized 1:1 to receive upadacitinib 15 mg (121 and 120 patients in Measure Up 1 and Measure Up 2, respectively) or 30 mg (123 and 121 patients) in a double-blinded manner. MAIN OUTCOMES AND MEASURES Safety and efficacy, including 75% improvement in the Eczema Area and Severity Index and Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) with 2 or greater grades of improvement, were assessed. Results Measure Up 1 and Measure Up 2 included a total of 1609 patients (mean [SD] age, 33.8 [15.6] years; 727 women [45.2%]; 882 men [54.8%]). Efficacy at week 16 was maintained through week 52. At week 52, 75% improvement in the Eczema Area and Severity Index was achieved by 82.0% (95% CI, 77.0%-86.9%) and 79.1% (95% CI, 73.9%-84.4%) of patients continuing the 15-mg dose and 84.9% (95% CI, 80.3%-89.5%) and 84.3% (95% CI, 79.6%-89.0%) of patients continuing the 30-mg dose (for Measure Up 1 and Measure Up 2, respectively); Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) with 2 or greater grades of improvement was achieved by 59.2% (95% CI, 52.9%-65.5%) and 52.6% (95% CI, 46.2%-59.1%) and 62.5% (95% CI, 56.3%-68.7%) and 65.1% (95% CI, 58.9%-71.2%) of patients in the Measure Up 1 and Measure Up 2 studies, respectively. Treatment discontinuation due to adverse events was low overall but was slightly higher for the upadacitinib 30-mg dose. Both upadacitinib doses were well tolerated with no new safety signals. CONCLUSIONS AND RELEVANCE In this analysis of follow-up data from 2 randomized clinical trials, longer-term treatment of adolescents and adults with moderate to severe atopic dermatitis with upadacitinib demonstrated a favorable benefit-risk profile, with sustained efficacy responses through 52 weeks.

Background: Atopic dermatitis (AD) is severely burdensome, and there has been poor characterization of any differences in impact based on the area affected.Objective: To estimate the prevalence and HRQoL impact of head/face/neck/hand (HFNH) involvement among patients with moderate-to-severe atopic dermatitis.Methods: All TARGET-DERM AD registry patients with moderate/severe Investigator Global Assessment (vIGA-AD) were assessed using the Patient Oriented SCORing Atopic Dermatitis, Patient Oriented Eczema Measure (POEM) and the (Children's) Dermatology Life Quality Index ((C)DLQI).Results: 541 participants met the criteria (75.0% adults) and 84% (N = 453) reported HFNH involvement. HFNH and non-HFNH involved participants had similar characteristics; 55.2% female and 46.9% White. Compared to the non-HFNH involved, the involved had severe vIGA-AD (28.5% vs 16.3%, P = .02) and higher median body surface area affected (15% vs 10%, P # .01) and were twice as likely to have higher (C) DLQI and POEM scores.Limitations: This was an analysis of real-world and patient reported outcome data.Conclusion: Real-world HFNH involved AD patients were associated with significantly worse quality of life, POEM/(C)DLQI, and more severe disease. Detailed assessments of specific areas affected by AD are needed to personalize treatment.

Atopic dermatitis (AD) is a common, chronic, inflammatory skin condition that affects people of all ages, races, and ethnicities. The condition is heterogeneous in both clinical presentation (phenotype) and underlying pathobiology (endotype). Atopic dermatitis diagnosis, assessment, and monitoring rely on clinical evaluation because there are no definitive biomarkers for AD. This review addresses variation in the clinical presentation of AD across the spectrum of Fitzpatrick skin types, with an emphasis on clinical evaluation challenges in patients with skin of color. We present photographs from phase 3 clinical trials that evaluated the safety and efficacy of upadacitinib among patients with moderate-to-severe AD and demonstrate the challenges in evaluating the clinical signs of AD (erythema and excoriation in patients with dark skin types and lichenification in those with light skin types) by illustrating the changes in clinical signs and symptoms that can be achieved with targeted systemic therapies.

Primary results from the Measure Up 1 and Measure Up 2 studies demonstrated upadacitinib efficacy and safety through 16 weeks in patients with atopic dermatitis. Longer-term outcomes remain unknown.To evaluate long-term (52 weeks) efficacy and safety of upadacitinib treatment in patients with atopic dermatitis.Measure Up 1 and Measure Up 2 are ongoing double-blind, placebo-controlled, replicate phase 3 randomized clinical trials that include adults and adolescents with moderate to severe atopic dermatitis at 151 and 154 centers, respectively. Cutoffs for this analysis were December 21, 2020 (Measure Up 1), and January 15, 2021 (Measure Up 2).Patients were randomized 1:1:1 to receive once-daily oral upadacitinib 15 mg, 30 mg, or placebo. At week 16, patients randomized at baseline to receive upadacitinib 15 mg (273 and 260 patients in Measure Up 1 and Measure Up 2, respectively) and 30 mg (270 and 268 patients) continued assigned treatment; placebo-treated patients were rerandomized 1:1 to receive upadacitinib 15 mg (121 and 120 patients in Measure Up 1 and Measure Up 2, respectively) or 30 mg (123 and 121 patients) in a double-blinded manner.Safety and efficacy, including 75% improvement in the Eczema Area and Severity Index and Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) with 2 or greater grades of improvement, were assessed.Measure Up 1 and Measure Up 2 included a total of 1609 patients (mean [SD] age, 33.8 [15.6] years; 727 women [45.2%]; 882 men [54.8%]). Efficacy at week 16 was maintained through week 52. At week 52, 75% improvement in the Eczema Area and Severity Index was achieved by 82.0% (95% CI, 77.0%-86.9%) and 79.1% (95% CI, 73.9%-84.4%) of patients continuing the 15-mg dose and 84.9% (95% CI, 80.3%-89.5%) and 84.3% (95% CI, 79.6%-89.0%) of patients continuing the 30-mg dose (for Measure Up 1 and Measure Up 2, respectively); Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) with 2 or greater grades of improvement was achieved by 59.2% (95% CI, 52.9%-65.5%) and 52.6% (95% CI, 46.2%-59.1%) and 62.5% (95% CI, 56.3%-68.7%) and 65.1% (95% CI, 58.9%-71.2%) of patients in the Measure Up 1 and Measure Up 2 studies, respectively. Treatment discontinuation due to adverse events was low overall but was slightly higher for the upadacitinib 30-mg dose. Both upadacitinib doses were well tolerated with no new safety signals.In this analysis of follow-up data from 2 randomized clinical trials, longer-term treatment of adolescents and adults with moderate to severe atopic dermatitis with upadacitinib demonstrated a favorable benefit-risk profile, with sustained efficacy responses through 52 weeks.ClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1) and NCT03607422 (Measure Up 2).

Background: Boosted protease inhibitor (PI) plus two nucleoside reverse transcriptase inhibitors (NRTI) is the preferred strategy for second-line anti-retroviral therapy (ART2) after the failure of a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line (ART1). We aim at comparing lopinavir/ritonavir (LPV/r) and atazanavir plus ritonavir (ATV/r) ART2 in routine clinical practice in Buenos Aires. Methods & Materials: Data were retrospectively collected from 3 clinical sites. Inclusion criteria: HIV+, ≥18 years; ART1 containing NNRTI + 2-3 N(t)RTIs; switched to ATV/r or LPV/r ART2 by treating physician due to virologic failure (2 pVL > 400 or 1 pVL >1000 at least 180 days after ART2 initiation); ART1 from January-2007 and switch to ART2 before June-2015. Exclusion criteria: any use of ddI + TDF or ddI + d4T in ART2; other PIs, etravirine, maraviroc, enfuvirtide or integrase inhibitors previous or concomitant to ART2. Three outcomes were evaluated at week 48: ART2 discontinuation, virologic failure in those not discontinued and, treatment failure with discontinuations considered as failures. Predictors for each outcome were assessed through logistic regression. Results: 162 patients were included: 93 patients (57%) received ATV/r based ART2 and 69 (43%) LPV/r. Patients on LPV/r were younger (36.0 vs. 39.2 years), had lower CD4 counts (179 vs. 229 cels/uL) and higher pVL (4.3 vs. 3.9 log copies/uL). Before week 48, 11 patients on ATV/r (11.8%) and 15 on LPV/r (21.7%) discontinued ART2, mainly due to gastrointestinal adverse events. Virologic failure in those not discontinued was similar for ATV/r and LPV/r (18% vs 22%). Treatment failure was observed in 24.7% and 36.2% respectively. After adjusting for sex, age and baseline pVL, LPV/r use was no longer associated with treatment failure (OR: 1.19, 95%CI: 0.52-2.73, p: 0.686) being pVL the main predictor (OR for pVL ≥ 4 logs: 2.71, 95%CI: 1.16-6.32, p: 0.021) Conclusion: In this retrospective cohort study of patients receiving ATV/r or LPV/r after failure of ART1, we found an increased risk of treatment discontinuation in LPV/r ART2 while virologic suppression in those on therapy was similar with both PIs. The main driver of virologic failure was pVL at start of ART2.

Background: Palivizumab is the standard immunoprophylaxis against serious disease due to respiratory syncytial virus infection. Current evidence-based prophylaxis guidelines may not address certain children with CHD within specific high-risk groups or clinical/management settings. Methods: An international steering committee of clinicians with expertise in paediatric heart disease identified key questions concerning palivizumab administration; in collaboration with an additional international expert faculty, evidence-based recommendations were formulated using a quasi-Delphi consensus methodology. Results: Palivizumab prophylaxis was recommended for children with the following conditions: < 2 years with unoperated haemodynamically significant CHD, who are cyanotic, who have pulmonary hypertension, or symptomatic airway abnormalities; < 1 year with cardiomyopathies requiring treatment; in the 1st year of life with surgically operated CHD with haemodynamically significant residual problems or aged 1-2 years up to 6 months postoperatively; and on heart transplant waiting lists or in their 1st year after heart transplant. Unanimous consensus was not reached for use of immunoprophylaxis in children with asymptomatic CHD and other co-morbid factors such as arrhythmias, Down syndrome, or immunodeficiency, or during a nosocomial outbreak. Challenges to effective immunoprophylaxis included the following: multidisciplinary variations in identifying candidates with CHD and prophylaxis compliance; limited awareness of severe disease risks/burden; and limited knowledge of respiratory syncytial virus seasonal patterns in subtropical/tropical regions. Conclusion: Evidence-based immunoprophylaxis recommendations were formulated for subgroups of children with CHD, but more data are needed to guide use in tropical/subtropical countries and in children with certain co-morbidities.

BACKGROUND:Respiratory syncytial virus (RSV) is a major public health burden worldwide. We aimed to review the current literature on the incidence and mortality of severe RSV in children globally.METHODS:Systematic literature review and meta-analysis of published data from 2000 onwards, reporting on burden of acute respiratory infection (ARI) due to RSV in children. Main outcomes were hospitalization for severe RSV-ARI and death.RESULTS:Five thousand two hundred and seventy-four references were identified. Fifty-five studies were included from 32 countries. The global RSV-ARI hospitalization estimates, reported per 1,000 children per year (95% Credible Interval (CrI), were 4.37 (2.98, 6.42) among children <5 years, 19.19 (15.04, 24.48) among children <1 year, 20.01 (9.65, 41.31) among children <6 months and 63.85 (37.52, 109.70) among premature children <1 year. The RSV-ARI global case-fatality estimates, reported per 1,000 children, (95% Crl) were 6.21 (2.64, 13.73) among children <5 years, 6.60 (1.85, 16.93) for children <1 year, and 1.04 (0.17, 12.06) among preterm children <1 year.CONCLUSIONS:A substantial proportion of RSV-associated morbidity occurs in the first year of life, especially in children born prematurely. These data affirm the importance of RSV disease in the causation of hospitalization and as a significant contributor to pediatric mortality and further demonstrate gestational age as a critical determinant of disease severity. An important limitation of case-fatality ratios is the absence of individual patient characteristics of non-surviving patients. Moreover, case-fatality ratios cannot be translated to population-based mortality. Pediatr Pulmonol. 2017;52:556-569. © 2016 The Authors. Pediatric Pulmonology. Published by Wiley Periodicals, Inc.

Globally, respiratory syncytial virus (RSV) is the most common cause of serious lower respiratory tract infections (LRTIs) in young children, and is a major cause of hospital admission in children <1 year of age. The study evaluated the severity of RSV-associated LRTI disease among premature (<36 weeks gestational age (GA)) and term children <1 year of age and assessed the influence of GA on outcomes of RSV LRTI hospitalization in Central and Eastern Europe (CEE).

BACKGROUND:Preterm infants are at high risk of developing respiratory syncytial virus (RSV)-associated lower respiratory tract infection (LRTI). This observational epidemiologic study evaluated RSV disease burden and risk factors for RSV-associated LRTI hospitalization in preterm infants 33 weeks+0 days to 35 weeks+6 days gestational age not receiving RSV prophylaxis.METHODS:Preterm infants ≤6 months of age during RSV season (1 October 2013-30 April 2014) were followed at 72 sites across 23 countries from September 2013-July 2014 (study period). RSV testing was performed according to local clinical practice. Factors related to RSV-associated hospitalization for LRTI were identified using multivariable logistic regression with backward selection.RESULTS:Of the 2390 evaluable infants, 204 and 127 were hospitalized for LRTI during the study period and RSV season, respectively. Among these subjects, 64/204 and 46/127, respectively, were hospitalized for confirmed RSV LRTI. Study period and RSV season normalized RSV hospitalization rates (per 100 infant years) were 4.1 and 6.1, respectively. Factors associated with an increased risk of RSV-related LRTI hospitalization in multivariable analyses were smoking of family members (P<0.0001), non-hemodynamically significant congenital heart disease diagnosis (P = 0.0077), maternal age of ≤25 years at delivery (P = 0.0009), low maternal educational level (P = 0.0426), household presence of children aged 4 to 5 years (P = 0.0038), age on 1 October ≤3 months (P = 0.0422), and presence of paternal atopy (P<0.0001).CONCLUSIONS:During the 2013-2014 RSV season across 23 countries, for preterm infants 33-35 weeks gestation ≤6 months old on 1 October not receiving RSV prophylaxis, confirmed RSV LRTI hospitalization incidence was 4.1 per 100 infant years during the study period and 6.1 per 100 infant years during the RSV season. This study enhances the findings of single-country studies of common risk factors for severe RSV infection in preterm infants and suggests that combinations of 4-6 risk factors may be used to accurately predict risk of RSV hospitalization. These findings may be useful in the identification of infants most at risk of severe RSV infection.

Introduction: Lower respiratory tract infection (LRTI) is the leading cause of infant mortality globally in post-neonatal infants (i.e., 28-364 days of age). Respiratory syncytial virus (RSV) is the most commonly identified pathogen for infant LRTI and is the second most important cause of death in post-neonatal infants. Despite 50 years of RSV vaccine research, there is still no approved vaccine. Therefore, passive immunity with the monoclonal antibody palivizumab is the sole regulatory-approved option for the prevention of serious LRTI caused by RSV in pediatric patients at high risk of RSV disease.Methods: We conducted a comprehensive systematic literature review of randomized controlled trials (RCTs), open-label noncomparative clinical trials, and prospective observational studies/registries, and summarized the evidence related to the safety, efficacy, and effectiveness of palivizumab.Results: The efficacy of palivizumab, as measured by the relative reduction in RSVrelated hospitalization rate compared with placebo ranged from 39% to 78% (P<0.05) in the 2 pivotal RCTs. A meta-analysis of the RSVrelated hospitalization rate from 5 randomized placebo-controlled trials yielded an overall odds ratio of 0.41 (95% CI, 0.31-0.55) in favor of palivizumab prophylaxis over placebo (P<0.00001). Low rates of RSV-related hospitalizations were observed in palivizumab recipients consistently over time in more than 42,000 pediatric subjects across 7 RCTs, 4 open-label non-comparative trials, and 8 observational studies/registries conducted in 34 countries. In addition, among palivizumabprophylaxed subjects with breakthrough RSV LRTI, rates of intensive care unit admission and mechanical ventilation from RSV hospitalization also were low and consistent across studies. With respect to safety, no differences were observed between palivizumab and placebo in the blinded RCTs. Conclusion: Rates of RSV hospitalizations and RSV hospitalization-related endpoints in pediatric subjects who received prophylaxis with palivizumab were low and constant over time and across RCTs, open-label noncomparative trials, and observational studies/registries.

Background: Cardiovascular disease (CVD) causes significant morbidity and mortality in HIV-infected individuals. Advancing age, chronic HIV-associated inflammation and antiretroviral therapy in part contributes to the increased risk of CVD in these patients. Aim: This study aimed to compare the CVD- and HIV-related morbidity of subjects prior to initiating an non-nucleoside reverse transcriptase inhibitor (NNRTI)- versus a protease inhibitor (PI)-based HAART regimen. Methods: Subjects in this retrospective, observational study of medical claims data representing HIV-infected beneficiaries from May 2000 to December 2009 were assigned either to a PI initiator group (n = 2192) or to a NNRTI initiator group (n = 3338). The case mix similarities and differences between the two groups were compared. Results: More subjects in the PI group had previous treatment with nucleoside reverse transcriptase inhibitor therapy or with the fusion inhibitor enfuvirtide, whereas more subjects in the NNRTI group had prior treatment with lamivudine plus zidovudine. Uncontrolled Type 2 diabetes, substance abuse, drug dependence, cardiovascular morbidity, heart failure, nonhypertension kidney dysfunction, depression, AIDS-related diagnosis, Kaposi‘s sarcoma, candidiasis and cachexia were observed more often in the PI group. Subjects in the PI group were more likely to be receiving medications for AIDS conditions. Only smoking cessation medication showed a higher prevalence in the NNRTI group. Conclusion: Subjects initiating PI-based versus NNRTI-based therapy had a greater prevalence of specific comorbidities that may adversely affect CVD risk profile.

BACKGROUND:Antiretroviral therapy is associated with adverse events (AEs). The most frequently reported AE associated with lopinavir/ritonavir (LPV/r) containing regimens is diarrhea. The objective of this meta-analysis is to describe the incidence, prevalence, and duration of diarrhea in individuals taking LPV/r.METHODS:This is a meta-analysis of Abbott-conducted clinical trials. Inclusion criteria included prospective randomized clinical trials with the LPV/r tablet formulation and had AE data (moderate/severe diarrhea) available through 48 weeks of treatment.RESULTS:Three trials (total 1469 participants) met the inclusion criteria. In all, 11.2% of participants reported moderate/severe diarrhea by week 8, with median time to resolution of 7.4 weeks. The overall 48-week incidence of moderate/severe diarrhea was 15.5%. The discontinuation rate due to moderate/severe diarrhea was 1.3%.CONCLUSIONS:Moderate/severe diarrhea occurred in less than 1 in 6 participants taking LPV/r, typically started in the first 8 weeks of treatment and infrequently resulted in premature discontinuation.