Doravirine plus lamivudine two-drug regimen as maintenance antiretroviral therapy in people living with HIV: a French observational study.

BACKGROUND: Two-drug regimens based on integrase strand transfer inhibitors (INSTIs) and boosted PIs have entered recommended ART. However, INSTIs and boosted PIs may not be suitable for all patients. We aimed to report our experience with doravirine/lamivudine as maintenance therapy in people living with HIV (PLWH) followed in French HIV settings. METHODS: This observational study enrolled all adults who initiated doravirine/lamivudine between 1 September 2019 and 31 October 2021, in French HIV centres participating in the Dat'AIDS cohort. The primary outcome was the rate of virological success (plasma HIV-RNA < 50 copies/mL) at Week (W)48. Secondary outcomes included: rate of treatment discontinuation for non-virological reasons, evolution of CD4 count and CD4/CD8 ratio over follow-up. RESULTS: Fifty patients were included, with 34 (68%) men; median age: 58 years (IQR 51-62), ART duration: 20 years (13-23), duration of virological suppression: 14 years (8-19), CD4 count: 784 cells/mm3 (636-889). Prior to switching, all had plasma HIV-RNA < 50 copies/mL. All but three were naive to doravirine, and 36 (72%) came from a three-drug regimen. Median follow-up was 79 weeks (IQR 60-96). Virological success rate at W48 was 98.0% (95% CI 89.4-99.9). One virological failure occurred at W18 (HIV-RNA = 101 copies/mL) in a patient who briefly discontinued doravirine/lamivudine due to intense nightmares; there was no resistance at baseline and no resistance emergence. There were three strategy discontinuations for adverse events (digestive disorders: n = 2; insomnia: n = 1). There was no significant change in CD4/CD8 ratio, while CD4 T cell count significantly increased. CONCLUSIONS: These preliminary findings suggest that doravirine/lamivudine regimens can maintain high levels of viral suppression in highly ART-experienced PLWH with long-term viral suppression, and good CD4+ T cell count.

Abnormal T-cell phenotype in episodic angioedema with hypereosinophilia (Gleich syndrome): Frequency, clinical implication, and prognosis.

BACKGROUND: Episodic angioedema with eosinophilia (EAE) (Gleich syndrome) is a rare disorder consisting of recurrent episodes of angioedema, hypereosinophilia, and frequent elevated serum IgM level. METHODS: We conducted a retrospective multicenter nationwide study regarding the clinical spectrum and therapeutic management of patients with EAE in France. RESULTS: A total of 30 patients with a median age at diagnosis of 41 years (range, 5-84) were included. The median duration of each crisis was 5.5 days (range, 1-90), with swelling affecting mainly the face and the upper limbs. Total serum IgM levels were increased in 20 patients (67%). Abnormal T-cell immunophenotypes were detected in 12 patients (40%), of whom 5 (17%) showed evidence of clonal T-cell receptor gamma locus gene (TRG) rearrangement. The median duration of follow-up was 53 months (range, 31-99). The presence of an abnormal T-cell population was the sole factor associated with a shorter time to flare (hazard ratio, 4.15; 95% confidence interval, 1.18-14.66; P = .02). At last follow-up, 3 patients (10%) were able to have all treatments withdrawn and 11 (37%) were in clinical and biologic remission with less than 10 mg of prednisone daily. CONCLUSION: EAE is a heterogeneous condition that encompasses several disease forms. Although patients usually respond well to glucocorticoids, those with evidence of abnormal T-cell phenotype have a shorter time to flare.

One-Year Sequelae and Quality of Life in Adults with Meningococcal Meningitis: Lessons from the COMBAT Multicentre Prospective Study.

INTRODUCTION: COMBAT is a prospective, multicentre cohort study that enrolled consecutive adults with community-acquired bacterial meningitis (CABM) in 69 participating centres in France between February 2013 and July 2015 and followed them for 1 year. METHODS: Patients aged at least 18 years old, hospitalised with CABM were followed during their hospitalisation and then contacted by phone 12 months after enrolment. Here we present the prevalence of sequelae at 12 months in a subgroup of patients with meningococcal meningitis. RESULTS: Five of the 111 patients with meningococcal meningitis died during initial hospitalisation and two died between discharge and 12 months, leaving 104 patients alive 1 year after enrolment, 71 of whom provided 12-month follow-up data. The median age was 30.0 years and 54.1% of the patients had no identified risk factor for meningitis. More than 30% reported persistent headache, more than 40% were not satisfied with their sleep and 10% had concentration difficulties. Hearing loss was present in about 15% of the patients and more than 30% had depressive symptoms. About 13% of the patients with a previous professional activity had not resumed work. On the SF-12 Health Survey, almost 50% and 30% had physical component or mental component scores lower than the 25th percentile of the score distribution in the French general population. There was a non-significant improvement in the patients' disability scores from hospital discharge to 12 months (p = 0.16), but about 10% of the patients had residual disability. CONCLUSIONS: Although most patients in our cohort survive meningococcal meningitis, the long-term burden is substantial and therefore it is important to ensure a prolonged follow-up of survivors and to promote preventive strategies, including vaccination. TRIAL REGISTRATION: ClinicalTrial.Gov identification number NCT01730690.

Incidence of cervical, breast and colorectal cancers between 2010 and 2015 in people living with HIV in France.

BACKGROUND: We aimed to evaluate the incidence rates between 2010 and 2015 for invasive cervical cancer (ICC), breast cancer (BC), and colorectal cancer (CRC) in people living with HIV (PLWH) in France, and to compare them with those in the French general population. These cancers are targeted by the national cancer-screening program. SETTING: This is a retrospective study based on the longitudinal data of the French Dat'AIDS cohort. METHODS: Standardized incidence ratios (SIR) for ICC and BC, and incidence rates for all three cancers were calculated overall and for specific sub-populations according to nadir CD4 cell count, HIV transmission category, HIV diagnosis period, and HCV coinfection. RESULTS: The 2010-2015 CRC incidence rate was 25.0 [95% confidence interval (CI): 18.6-33.4] per 100,000 person-years, in 44,642 PLWH (both men and women). Compared with the general population, the ICC incidence rate was significantly higher in HIV-infected women both overall (SIR = 1.93, 95% CI: 1.18-3.14) and in the following sub-populations: nadir CD4 ≤ 200 cells/mm3 (SIR = 2.62, 95% CI: 1.45-4.74), HIV transmission through intravenous drug use (SIR = 5.14, 95% CI: 1.93-13.70), HCV coinfection (SIR = 3.52, 95% CI: 1.47-8.47) and HIV diagnosis before 2000 (SIR = 2.06, 95% CI: 1.07-3.97). Conversely, the BC incidence rate was significantly lower in the study sample than in the general population (SIR = 0.56, 95% CI: 0.42-0.73). CONCLUSION: The present study showed no significant linear trend between 2010 and 2015 in the incidence rates of the three cancers explored in the PLWH study sample. Specific recommendations for ICC screening are still required for HIV-infected women and should focus on sub-populations at greatest risk.

Dolutegravir-based dual maintenance regimens combined with lamivudine/emtricitabine or rilpivirine: risk of virological failure in a real-life setting.

BACKGROUND: Maintenance ART with dolutegravir-based dual regimens have proved their efficacy among HIV-1-infected subjects in randomized trials. However, real-life data are scarce, with limited populations and follow-up. OBJECTIVES: We assessed virological failure (VF) and resistance-associated mutations (RAMs) on dolutegravir maintenance regimens in combination with rilpivirine or with lamivudine or emtricitabine (xTC) and analysed the factors associated with VF. METHODS: Between 2014 and 2018, all HIV-1-infected adults included in the Dat'AIDS cohort and starting dolutegravir/rilpivirine or dolutegravir/xTC as a maintenance dolutegravir-based dual regimen were selected. VF was defined as two consecutive HIV RNA values >50 copies/mL or a single value >400 copies/mL. We compared cumulative genotypes before initiation of a maintenance dolutegravir-based dual regimen with genotype at VF. RESULTS: We analysed 1374 subjects (799 on dolutegravir/rilpivirine and 575 on dolutegravir/xTC) with a median follow-up of 20 months (IQR = 11-31) and 19 months (IQR = 11-31), respectively. VF occurred in 3.8% (n = 30) of dolutegravir/rilpivirine subjects and 2.6% (n = 15) of dolutegravir/xTC subjects. Among subjects receiving dolutegravir/rilpivirine, two genotypes harboured emerging RAMs at VF: E138K on NNRTI (n = 1); and E138K+K101E on NNRTI and N155H on INSTI (n = 1). Among subjects receiving dolutegravir/xTC, no new RAM was detected. The only predictive factor of VF on dolutegravir/rilpivirine was the history of failure on an NNRTI-based regimen (adjusted HR = 2.97, 95% CI = 1.28-6.93). No factor was associated with VF on dolutegravir/xTC. CONCLUSIONS: In this large real-life cohort, dolutegravir/rilpivirine and dolutegravir/xTC sustained virological suppression and were associated with a low rate of VF and RAM emergence. Careful virological screening is essential before switching to dolutegravir/rilpivirine in virologically suppressed patients with a history of NNRTI therapy.

Spectrum and Incidence Trends of AIDS- and Non-AIDS-Defining Cancers between 2010 and 2015 in the French Dat'AIDS Cohort.

BACKGROUND: Cancer risk is higher in people living with HIV (PLWH) compared with the general population, and cancers related to age are expected to be most prevalent. METHODS: We determined the spectrum and incidence rates of AIDS-defining cancers (ADC) and non-AIDS-defining cancers (NADC) and of lung, Hodgkin lymphoma (HL), head and neck (HNC), colon-rectum, anal, liver, breast, prostate, and urinary bladder cancers between January 2010 and December 2015 in the French Dat'AIDS cohort. Incidence rates were calculated by year and compared using the χ 2 test for linear trend. Standardized incidence ratios [SIR (95% confidence interval)] were calculated relative to the French general population. RESULTS: Among 44,642 patients, corresponding to 180,216.4 person-years (PY), 1,440 cancer cases occurred in 1,314 patients. ADC incidence was 191.4 (172.3-212.7)/105 PY and declined over time overall and in men, whereas NADC incidence was higher [548.8 (515.6-584.1)/105 PY] and did not change. In men, non-Hodgkin lymphoma was the most common cancer, but prostate cancer had the highest incidence among NADCs. Breast cancer was the most common cancer in women. SIRs were higher for cervical cancer [1.93 (1.18-3.14)], HNC in women [2.4 (1.4-4.2)], liver [overall: 3.8 (3.1-4.6); men: 3.2 (2.5-4.0); women: 12.9 (8.3-20.0)], and HL [overall: 13.8 (11.1-17.1); men: 16.2 (12.9-20.4); women: 6.2 (3.22-11.9)] but lower for lung [overall: 0.7 (0.6-0.9); men: 0.7 (0.5-0.8)], prostate [0.6 (0.5-0.7)], and breast cancers [0.6 (0.4-0.7)]. CONCLUSIONS: Spectrum of NADCs has changed, with prostate and breast cancers becoming the most common despite their lower SIR. IMPACT: These results confirm the need to maintain regular epidemiologic cancer monitoring in order to update screening guidelines.

Increasing prevalence and local transmission of non-B HIV-1 subtypes in the French Antilles and French Guiana between 1995 and 2018.

The Caribbean and South American French Overseas Territories (CSAFOT) are the regions most heavily affected by the Human Immunodeficiency Virus type 1 (HIV-1) epidemic in France. Although dominated by HIV-1 subtype B, the detection of non-B subtypes and the great proportion of HIV-positive persons born abroad demonstrated the potential for local spread of non-B subtype strains in CSAFOT. To reconstruct the epidemiologic dynamics of major non-B subtype clusters spreading in CSAFOT, we conducted phylogenetic and evolutionary analyses of 2,523 HIV-1 pol sequences collected from patients living in Martinique, Guadeloupe, and French Guiana from 1995 to 2018. A large variety of HIV-1 non-B subtype strains (eight subtypes, twelve CRFs, and multiple URFs) have been introduced in CSAFOT and their prevalence significantly increases over time in Martinique and Guadeloupe. We identified twelve major transmission networks of non-B subtypes (CRF02_AG and subtypes A3, C, D, and F1) that probably arose in Guadeloupe, Martinique, French Guiana, and mainland France between the late 1970s and the middle 2000s. Phylogeographic analyses support frequent non-B subtype viral transmissions within CSAFOT as well as transatlantic transmission between CSAFOT and mainland France. Domestic transmission networks of non-B subtype variants in CSAFOT comprise both men having sex with men and heterosexual individuals from different age groups. Different HIV-1 non-B subtype variants were sequentially introduced in CSAFOT between the late 1970s and the middle 2000s and are currently spreading through domestic, regional, and/or transatlantic networks of individuals from different age and risk groups.

Multimorbidity in Elderly Persons According to the Year of Diagnosis of Human Immunodeficiency Virus Infection: A Cross-sectional Dat'AIDS Cohort Study.

BACKGROUND: We assessed prevalence of multimorbidity (MM) according to year of human immunodeficiency virus (HIV) diagnosis in elderly people living with HIV (PLWH). METHODS: This was a cross-sectional study of MM in PLWH aged ≥70 years from the Dat'AIDS French multicenter cohort. MM was defined as at least 3 coexistent morbidities of high blood pressure, diabetes mellitus, osteoporosis, non-AIDS cancer, chronic renal failure, cardiovascular and cerebrovascular disease, obesity, undernutrition, or hypercholesterolemia. Logistic regression models evaluated the association between MM and calendar periods of HIV diagnosis (1983-1996, 1997-2006, and 2007-2018). The secondary analysis evaluated MM as a continuous outcome, and a sensitivity analysis excluded PLWH with nadir CD4 count <200 cells/µL. RESULTS: Between January 2017 and September 2018, 2476 PLWH were included. Median age was 73 years, 75% were men, median CD4 count was 578 cells/µL, and 94% had controlled viremia. MM prevalence was 71%. HBP and hypercholesterolemia were the most prevalent comorbidities. After adjustment for age, gender, smoking status, hepatitis C and hepatitis B virus coinfection, group of exposure, nadir CD4 count, CD4:CD8 ratio, and last CD4 level, calendar period of diagnosis was not associated with MM (P = .169). MM was associated with older age, CD4/CD8 ratio <0.8, and nadir CD4 count <200 cells/µL. Similar results were found with secondary and sensitivity analyses. CONCLUSIONS: MM prevalence was high and increased with age, low CD4/CD8 ratio, and nadir CD4 count <200 cells/µL but was not associated with calendar periods of HIV diagnosis. Known duration of HIV diagnosis does not seem to be a criterion for selecting elderly PLWH at risk of MM.

Impact of an SMS reminder service on outpatient clinic attendance rates by patients with HIV followed-up at Pointe-à-Pitre University Hospital.

OBJECTIVE: By the end of 2014, 23% of people living with HIV (PWHIV) who had had a scheduled appointment at our outpatient clinic had not attended. We implemented an SMS reminder service and assessed its impact on medical consultation-attendance rate. METHODS: The intervention was directed at all PWHIV with a scheduled appointment between March and April 2015 at our infectious diseases department. Two days before the scheduled visit, an appointment reminder SMS was sent to every other patient at random. On the visit day, a questionnaire was used to determine patient perceptions regarding the SMS. RESULTS: A total of 224 patients (126 males, 98 females, mean age 52 years, 94% taking anti-retroviral therapy) were selected to take part in the study. The medical consultation-attendance rate was 76% in the SMS reminder read group (87 patients) and 72% in the SMS reminder not sent or not read group (137 patients, P=0.6). Among the 66 SMS reminder read patients who attended their consultation and answered the questionnaire, 51% reported that the SMS had contributed to their attendance. CONCLUSION: Sending an SMS reminder had no significant impact on clinic attendance rates. This may have been due in part to the sociocultural characteristics of our patients. Further research should investigate other tools to improve attendance rates.

Outbreak of Chikungunya in the French Caribbean Islands of Martinique and Guadeloupe: Findings from a Hospital-Based Surveillance System (2013-2015).

Chikungunya virus (CHIKV) emerged in the Caribbean island of Saint-Martin in December 2013. We implemented a hospital-based surveillance system to detect and describe CHIKV cases including severe forms of the infection and deaths in the islands of Martinique and Guadeloupe. A case was defined as a patient with a CHIKV laboratory confirmation cared for in a public hospital for chikungunya for at least 24 hours, and a severe CHIKV case was defined as a CHIKV case presenting one or more organ failures. Sociodemographic, clinical, and laboratory data were collected and cases classified into severe or nonsevere based on medical records. From December 2013 to January 2015, a total of 1,836 hospitalized cases were identified. Rate of hospital admissions for CHIKV infection was 60 per 10,000 suspected clinical CHIKV cases and severity accounted for 12 per 10,000. A total of 74 deaths related to CHIKV infection occurred. Infants and elderly people were more frequently hospitalized compared with others and severity was more frequently reported in elderly subjects and subjects with underlying health condition. Fifteen neonatal infections consecutive to mother-to-child transmission were diagnosed, seven of which were severe. The most vulnerable groups of the population, such as the elderly, infants, individuals with comorbidities, and pregnant women, should remain the main targets of public health priorities.

Community-acquired meningitis caused by a CG86 hypervirulent Klebsiella pneumoniae strain: first case report in the Caribbean.

BACKGROUND: Community-acquired bacterial meningitis due to Klebsiella pneumoniae has mainly been described in Southeast Asia and has a poor prognosis. Severe invasive infections caused by K. pneumoniae, including meningitis, are often due to hypervirulent strains (hvKP), which are characterized by capsular serotypes K1 and K2, a gene responsible for hypermucoviscosity, and the cluster for synthesis of the siderophore aerobactin. CASE PRESENTATION: A 55 year old man with a history of essential hypertension, benign prostate hyperplasia, hyperlipidemia, obstructive sleep apnea, and chronic alcoholism was admitted for meningitis due to Klebsiella pneumoniae with a wild-type susceptibility profile. Its genomic features were consistent with a capsular K2 strain belonging to clonal group 86 (CG86) displaying the large virulence of Klebsiella plasmid (pLVPK) with heavy metal resistance gene clusters, aerobactin, rmpA. CONCLUSION: This is the first case of community-acquired meningitis caused by a hypervirulent strain of hvKP ever reported in the Caribbean.

Performance Testing of PCR Assay in Blood Samples for the Diagnosis of Toxoplasmic Encephalitis in AIDS Patients from the French Departments of America and Genetic Diversity of Toxoplasma gondii: A Prospective and Multicentric Study.

BACKGROUND: Toxoplasmic encephalitis in patients with AIDS is a life-threatening disease mostly due to reactivation of Toxoplasma gondii cysts in the brain. The main objective of this study was to evaluate the performance of real-time PCR assay in peripheral blood samples for the diagnosis of toxoplasmic encephalitis in AIDS patients in the French West Indies and Guiana. METHODOLOGY/PRINCIPAL FINDINGS: Adult patients with HIV and suspicion of toxoplasmic encephalitis with start of specific antitoxoplasmic therapy were included in this study during 40 months. The real-time PCR assay targeting the 529 bp repeat region of T. gondii was performed in two different centers for all blood samples. A Neighbor-Joining tree was reconstructed from microsatellite data to examine the relationships between strains from human cases of toxoplasmosis in South America and the Caribbean. A total of 44 cases were validated by a committee of experts, including 36 cases with toxoplasmic encephalitis. The specificity of the PCR assay in blood samples was 100% but the sensitivity was only 25% with moderate agreement between the two centers. Altered level of consciousness and being born in the French West Indies and Guiana were the only two variables that were associated with significantly decreased risk of false negative results with the PCR assay. CONCLUSION/SIGNIFICANCE: Our results showed that PCR sensitivity in blood samples increased with severity of toxoplasmic encephalitis in AIDS patients. Geographic origin of patients was likely to influence PCR sensitivity but there was little evidence that it was caused by differences in T. gondii strains. TRIAL REGISTRATION: ClinicalTrials.gov NCT00803621.

Severe Sepsis and Septic Shock Associated with Chikungunya Virus Infection, Guadeloupe, 2014.

During a 2014 outbreak, 450 patients with confirmed chikungunya virus infection were admitted to the University Hospital of Pointe-à-Pitre, Guadeloupe. Of these, 110 were nonpregnant adults; 42 had severe disease, and of those, 25 had severe sepsis or septic shock and 12 died. Severe sepsis may be a rare complication of chikungunya virus infection.

Factors Associated with Severe Leptospirosis, Martinique, 2010-2013.

To identify factors associated with disease severity, we examined 102 patients with quantitative PCR-confirmed leptospirosis in Martinique during 2010-2013. Associated factors were hypotension, chest auscultation abnormalities, icterus, oligo/anuria, thrombocytopenia, prothrombin time <68%, high levels of leptospiremia, and infection with L. interrogans serovar Icterohaemorrhagiae/Copenhageni.

Incidence and predictive factors of depression among patients with HIV infection in Guadeloupe: 1988-2009.

A retrospective cohort study was conducted to determine the incidence and the predictive factors of depression in a cohort of 2737 HIV/AIDS-infected patients in Guadeloupe followed for a total of 8402 patient-years. The incidence rate of first observed depression was 2.2 per 100 person-years (95% confidence interval [CI], 1.9-2.6). A single failure Cox proportional hazards model showed that the 1997-2000 inclusion period (hazard ratio [HR] = 1.60; 95% CI = 1.10-2.40;p = 0.01), the 2001-2009 inclusion period (HR = 1.50; 95% CI = 1.02-2.40;p = 0.04), the more advanced CDC stage (HR = 2.30; 95% CI = 1.30-3.10;p = 0.000) and the annual frequency of visits > 10 (HR = 2.30; 95% CI = 1.70-3.30;p = 0.000) were associated with an increased risk of depression. Incidence of depression in this HIV cohort was high and the hazard function showed three peaks of depression (2, 7 and 12 years). Physicians should be vigilant to psychological distress throughout life with HIV.

What is AIDS in Guadeloupe? A descriptive and comparative study.

Since the pathogen ecology differs between Caribbean regions, specific differences in the most frequent clinical presentations of acquired immunodeficiency syndrome (AIDS) may be expected. We therefore conducted the present retrospective cohort study in order to describe the main AIDS-defining events in Guadeloupe and to compare them with those observed in Metropolitan France and in French Guiana. We discuss the local pathogen ecology, the diagnostic limitations of hospitals in overseas territories and the drivers of the epidemic.

Serovar diversity of pathogenic Leptospira circulating in the French West Indies.

BACKGROUND: Leptospirosis is one of the most important neglected tropical bacterial diseases in Latin America and the Caribbean. However, very little is known about the circulating etiological agents of leptospirosis in this region. In this study, we describe the serological and molecular features of leptospires isolated from 104 leptospirosis patients in Guadeloupe (n = 85) and Martinique (n = 19) and six rats captured in Guadeloupe, between 2004 and 2012. METHODS AND FINDINGS: Strains were studied by serogrouping, PFGE, MLVA, and sequencing 16SrRNA and secY. DNA extracts from blood samples collected from 36 patients in Martinique were also used for molecular typing of leptospires via PCR. Phylogenetic analyses revealed thirteen different genotypes clustered into five main clades that corresponded to the species: L. interrogans, L. kirschneri, L. borgpetersenii, L. noguchi, and L. santarosai. We also identified L. kmetyi in at least two patients with acute leptospirosis. This is the first time, to our knowledge, that this species has been identified in humans. The most prevalent genotypes were associated with L. interrogans serovars Icterohaemorrhagiae and Copenhageni, L. kirschneri serovar Bogvere, and L. borgpetersenii serovar Arborea. We were unable to identify nine strains at the serovar level and comparison of genotyping results to the MLST database revealed new secY alleles. CONCLUSIONS: The overall serovar distribution in the French West Indies was unique compared to the neighboring islands. Typing of leptospiral isolates also suggested the existence of previously undescribed serovars.

Severe leptospirosis in hospitalized patients, Guadeloupe.

We evaluated prognostic factors for leptospirosis in 168 consecutive hospitalized patients in Guadeloupe. Factors independently associated with severity included chronic hypertension or chronic alcoholism, late initiation of antibacterial therapy, abnormal chest auscultation results, icterus, oligoanuria, disorders of consciousness, elevated aspartate aminotransferase levels, hyperamylasemia, and Leptospira interrogans serovar Icterohemorrhagiae.

Drug Hypersensitivity Syndrome in a West-Indian population.

Some studies have suggested an ethnic susceptibility to Hypersensitivity Syndrome. We did a 7-year-prospective study in Guadeloupe whose population is mainly of African ancestry, and has free access to modern care facilities. Most patients included were Afro-Caribbeans (26/28), and females (20/28). However, ethnic distribution did not reach significant conclusions. Annual incidence rate was estimated at 0.9/100,000. Medium incubation and duration were 33 and 66 days respectively. Two patients with grade 4 hepatitis died from the syndrome. Two thirds of the patients were given prednisone, which usually alleviated the systemic symptoms, but did not prevent their development (in 5 patients) nor death. Carbamazepine, allopurinol, and minocycline accounted for 2/3 of the cases. Sixty four percent of the causative prescriptions were judged inappropriate. DHS appeared as the most frequent type of severe systemic drug reaction in this population, and may largely be prevented by rational prescribing.