Barbara Hasse

Morbidity and Aging in HIV-Infected Persons: The Swiss HIV Cohort Study

BACKGROUND Patterns of morbidity and mortality among human immunodeficiency virus (HIV)-infected individuals taking antiretroviral therapy are changing as a result of immune reconstitution and improved survival. We studied the influence of aging on the epidemiology of non-AIDS diseases in the Swiss HIV Cohort Study. METHODS The Swiss HIV Cohort Study is a prospective observational cohort established in 1988 with continuous enrollment. We determined the incidence of clinical events (per 1000 person-years) from January 2008 (when a new questionnaire on non-AIDS-related morbidity was introduced) through December 2010. Differences across age groups were analyzed using Cox regression, adjusted for CD4 cell count, viral load, sex, injection drug use, smoking, and years of HIV infection. RESULTS Overall, 8444 (96%) of 8848 participants contributed data from 40,720 semiannual visits; 2233 individuals (26.4%) were aged 50-64 years, and 450 (5.3%) were aged ≥65 years. The median duration of HIV infection was 15.4 years (95% confidence interval [CI], 9.59-22.0 years); 23.2% had prior clinical AIDS. We observed 994 incident non-AIDS events in the reference period: 201 cases of bacterial pneumonia, 55 myocardial infarctions, 39 strokes, 70 cases of diabetes mellitus, 123 trauma-associated fractures, 37 fractures without adequate trauma, and 115 non-AIDS malignancies. Multivariable hazard ratios for stroke (17.7; CI, 7.06-44.5), myocardial infarction (5.89; 95% CI, 2.17-16.0), diabetes mellitus (3.75; 95% CI, 1.80-7.85), bone fractures without adequate trauma (10.5; 95% CI, 3.58-30.5), osteoporosis (9.13; 95% CI, 4.10-20.3), and non-AIDS-defining malignancies (6.88; 95% CI, 3.89-12.2) were elevated for persons aged ≥65 years. CONCLUSIONS Comorbidity and multimorbidity because of non-AIDS diseases, particularly diabetes mellitus, cardiovascular disease, non-AIDS-defining malignancies, and osteoporosis, become more important in care of HIV-infected persons and increase with older age.

Pulmonary Arterial Hypertension Related to HIV Infection: Improved Hemodynamics and Survival Associated with Antiretroviral Therapy

This study aimed to assess the long-term course of pulmonary arterial hypertension related to infection with human immunodeficiency virus (PAHRH) and the influence of antiretroviral therapy (ART) on its characteristics. We retrospectively analyzed all 47 patients in the Swiss HIV Cohort Study in whom PAHRH was diagnosed. Among 35 patients who underwent follow-up Doppler echocardiography, the right ventricular systolic pressure over right atrial pressure gradient increased by a median of 25 mm Hg in 9 patients who had not received ART, decreased by a median of 3 mm Hg in 12 patients who had received nucleoside analogs, and decreased by a median of 21 mm Hg in 14 patients who had received highly active ART (HAART) (P<.005). Among all 47 patients, median duration of survival after PAHRH diagnosis was 2.7 years. HAART significantly decreased mortality due to PAHRH as well as other causes. This study suggests a beneficial effect of combination ART in patients with PAHRH.

Non-Hodgkin lymphoma incidence in the Swiss HIV Cohort Study before and after highly active antiretroviral therapy

Objective:To assess the long-term effect of HAART on non-Hodgkin lymphoma (NHL) incidence in people with HIV (PHIV). Design:Follow-up of the Swiss HIV Cohort Study (SHCS). Methods:Between 1984 and 2006, 12 959 PHIV contributed a total of 75 222 person-years (py), of which 36 787 were spent under HAART. Among these PHIV, 429 NHL cases were identified from the SHCS dataset and/or by record linkage with Swiss Cantonal Cancer Registries. Age- and gender-standardized incidence was calculated and Cox regression was used to estimate hazard ratios (HR). Results:NHL incidence reached 13.6 per 1000 py in 1993–1995 and declined to 1.8 in 2002–2006. HAART use was associated with a decline in NHL incidence [HR = 0.26; 95% confidence interval (CI), 0.20–0.33], and this decline was greater for primary brain lymphomas than other NHL. Among non-HAART users, being a man having sex with men, being 35 years of age or older, or, most notably, having low CD4 cell counts at study enrolment (HR = 12.26 for < 50 versus ≥ 350 cells/μl; 95% CI, 8.31–18.07) were significant predictors of NHL onset. Among HAART users, only age was significantly associated with NHL risk. The HR for NHL declined steeply in the first months after HAART initiation (HR = 0.46; 95% CI, 0.27–0.77) and was 0.12 (95% CI, 0.05–0.25) 7 to10 years afterwards. Conclusions:HAART greatly reduced the incidence of NHL in PHIV, and the influence of CD4 cell count on NHL risk. The beneficial effect remained strong up to 10 years after HAART initiation.

Prolonged Outbreak of Mycobacterium chimaera Infection After Open-Chest Heart Surgery

BACKGROUND Invasive Mycobacterium chimaera infections were diagnosed in 2012 in 2 heart surgery patients on extracorporeal circulation. We launched an outbreak investigation to identify the source and extent of the potential outbreak and to implement preventive measures. METHODS We collected water samples from operating theaters, intensive care units, and wards, including air samples from operating theaters. Mycobacterium chimaera strains were characterized by randomly amplified polymorphic DNA polymerase chain reaction (RAPD-PCR). Case detection was performed based on archived histopathology samples and M. chimaera isolates since 2006, and the patient population at risk was prospectively surveyed. RESULTS We identified 6 male patients aged between 49 and 64 years with prosthetic valve endocarditis or vascular graft infection due to M. chimaera, which became clinically manifest with a latency of between 1.5 and 3.6 years after surgery. Mycobacterium chimaera was isolated from cardiac tissue specimens, blood cultures, or other biopsy specimens. We were able also to culture M. chimaera from water circuits of heater-cooler units connected to the cardiopulmonary bypass, and air samples collected when the units were in use. RAPD-PCR demonstrated identical patterns among M. chimaera strains from heater-cooler unit water circuits and air samples, and strains in 2 patient clusters. CONCLUSIONS The epidemiological and microbiological features of this prolonged outbreak provided evidence for the airborne transmission of M. chimaera from contaminated heater-cooler unit water tanks to patients during open-heart surgery.

Suicide in HIV-Infected Individuals and the General Population in Switzerland, 1988–2008

OBJECTIVE High rates of suicide have been described in HIV-infected patients, but it is unclear to what extent the introduction of highly active antiretroviral therapy (HAART) has affected suicide rates. The authors examined time trends and predictors of suicide in the pre-HAART (1988-1995) and HAART (1996-2008) eras in HIV-infected patients and the general population in Switzerland. METHOD The authors analyzed data from the Swiss HIV Cohort Study and the Swiss National Cohort, a longitudinal study of mortality in the Swiss general population. The authors calculated standardized mortality ratios comparing HIV-infected patients with the general population and used Poisson regression to identify risk factors for suicide. RESULTS From 1988 to 2008, 15,275 patients were followed in the Swiss HIV Cohort Study for a median duration of 4.7 years. Of these, 150 died by suicide (rate 158.4 per 100,000 person-years). In men, standardized mortality ratios declined from 13.7 (95% CI=11.0-17.0) in the pre-HAART era to 3.5 (95% CI=2.5-4.8) in the late HAART era. In women, ratios declined from 11.6 (95% CI=6.4-20.9) to 5.7 (95% CI=3.2-10.3). In both periods, suicide rates tended to be higher in older patients, in men, in injection drug users, and in patients with advanced clinical stage of HIV illness. An increase in CD4 cell counts was associated with a reduced risk of suicide. CONCLUSIONS Suicide rates decreased significantly with the introduction of HAART, but they remain above the rate observed in the general population, and risk factors for suicide remain similar. HIV-infected patients remain an important target group for suicide prevention.

Prosthetic Valve Endocarditis and Bloodstream Infection Due to Mycobacterium chimaera

ABSTRACT Prosthetic valve endocarditis (PVE) due to fast-growing nontuberculous mycobacteria (NTM) has been reported anecdotally. Reports of PVE with slowly growing NTM, however, are lacking. We present here one case of PVE and one case of bloodstream infection caused by Mycobacterium chimaera. Randomly amplified polymorphic DNA (RAPD)-PCR indicated a relatedness of the two M. chimaera strains. Both patients had heart surgery 2 years apart from each other. A nosocomial link was not detected.

Efavirenz Intoxication Due to Slow Hepatic Metabolism

We describe a human immunodeficiency virus-positive woman who presented with severe psychosis while she was receiving therapy with efavirenz. Her plasma efavirenz level was excessively high. Genetic investigation showed that she was homozygous for the CYP2B6 G516T allele, resulting in slow hepatic metabolism. After the dosage of efavirenz was lowered, all neuropsychiatric symptoms subsided.

Successful Treatment with Miltefosine of Disseminated Cutaneous Leishmaniasis in a Severely Immunocompromised Patient Infected with HIV-1

We describe here a case of disseminated cutaneous leishmaniasis due to Leishmania major in a severely immunocompromised patient from Burkino Faso, Africa, who is infected with human immunodeficiency virus-1. The skin lesions failed to respond to full treatment courses of amphotericin B, sodium stibogluconate, and liposomal amphotericin B but were successfully treated with miltefosine, an alkylphosphocholine analogue.

Treatment-Naive Individuals Are the Major Source of Transmitted HIV-1 Drug Resistance in Men Who Have Sex With Men in the Swiss HIV Cohort Study

BACKGROUND Human immunodeficiency virus type 1 (HIV-1) transmitted drug resistance (TDR) can compromise antiretroviral therapy (ART) and thus represents an important public health concern. Typically, sources of TDR remain unknown, but they can be characterized with molecular epidemiologic approaches. We used the highly representative Swiss HIV Cohort Study (SHCS) and linked drug resistance database (SHCS-DRDB) to analyze sources of TDR. METHODS ART-naive men who have sex with men with infection date estimates between 1996 and 2009 were chosen for surveillance of TDR in HIV-1 subtype B (N = 1674), as the SHCS-DRDB contains pre-ART genotypic resistance tests for >69% of this surveillance population. A phylogeny was inferred using pol sequences from surveillance patients and all subtype B sequences from the SHCS-DRDB (6934 additional patients). Potential sources of TDR were identified based on phylogenetic clustering, shared resistance mutations, genetic distance, and estimated infection dates. RESULTS One hundred forty of 1674 (8.4%) surveillance patients carried virus with TDR; 86 of 140 (61.4%) were assigned to clusters. Potential sources of TDR were found for 50 of 86 (58.1%) of these patients. ART-naive patients constitute 56 of 66 (84.8%) potential sources and were significantly overrepresented among sources (odds ratio, 6.43 [95% confidence interval, 3.22-12.82]; P < .001). Particularly large transmission clusters were observed for the L90M mutation, and the spread of L90M continued even after the near cessation of antiretroviral use selecting for that mutation. Three clusters showed evidence of reversion of K103N or T215Y/F. CONCLUSIONS Many individuals harboring viral TDR belonged to transmission clusters with other Swiss patients, indicating substantial domestic transmission of TDR in Switzerland. Most TDR in clusters could be linked to sources, indicating good surveillance of TDR in the SHCS-DRDB. Most TDR sources were ART naive. This, and the presence of long TDR transmission chains, suggests that resistance mutations are frequently transmitted among untreated individuals, highlighting the importance of early diagnosis and treatment.

Long-term results of vascular graft and artery preserving treatment with negative pressure wound therapy in Szilagyi grade III infections justify a paradigm shift.

Objective:To present the first long-term results of Szilagyi III vascular infections treated by negative pressure wound therapy (NPWT) with graft preservation. Background Data:Szilagyi III infections are usually treated by graft/artery excision and secondary vascular/plastic reconstruction. Small series treated with NPWT without graft removal are reported with good short-term to midterm results. Methods:The outcomes of 44 polymorbid patients (mean age = 62 years) with Szilagyi III infections from 2002 to 2009 were analyzed. Thirteen of forty-four required intensive care unit treatment. Forty grafts (prosthetic = 24, vein = 3, biological = 13) and 9 native arteries were involved. Negative pressure wound therapy (VAC; KCI International, Amstelveen, Netherlands) was applied directly on grafts/arteries (negative pressure = 50–125 mm Hg) after radical debridement of infected tissue. Antibiotic treatment was initiated and adapted according to microbiology. Results:Median duration of NPWT was 33 days (IQR: 20–78), of hospital stay 32 (IQR: 20–82) days. All patients survived 30 days. One-year mortality was 16% (7/44). Long-term mortality after a mean follow-up of 43 months (SD: 21) was 41% (18/44).Complete wound healing was achieved in 91% (40/44). In 37 of 44 patients, grafts were preserved long-term without reinfection. There was no statistically significant difference in outcome between the various graft types involved. Conclusions:Vascular graft/arterial preserving treatment with NPWT in Szilagyi III infections was safe and effective with a very low short-term mortality. The majority of infected grafts were preserved without reinfection during a mean long-term follow-up of 4 years. This new treatment algorithm avoids major reconstructive surgery and should be used when dealing with Szilagyi III vascular infections.