Low pre-ART CD4 count is associated with increased risk of clinical progression or death even after reaching 500 CD4 cells/µL on ART.

INTRODUCTION: Clinical disadvantages of initiating ART at low CD4 counts have been clearly demonstrated but whether any excess risk remains even after reaching relatively high/safe CD4 levels remains unclear. We explore whether individuals starting ART with <500 CD4 cells/µL who increased their CD4 count above this level, have, from this point onwards, similar risk of clinical progression to serious AIDS/non-AIDS events or death with individuals starting ART with ≥500 CD4 cells/µL. METHODS: Data were derived from a multicenter cohort (AMACS). Adults, starting PI, NNRTI or INSTI based ART, in or after 2000 were eligible, provided they started ART with ≥500 ("High CD4") or started with CD4 <500 cells/µL but surpassed this threshold while on ART ("Low CD4"). Baseline was the date of ART initiation ("High CD4") or of first reaching 500 CD4 cells/µL ("Low CD4"). Survival analysis, allowing for competing risks, was used to explore the risk of progression to study's endpoints. RESULTS: The study included 694 persons in the "High CD4" and 3,306 in the "Low CD4" group. Median (IQR) follow-up was 66 (36, 106) months. In total, 257 events (40 AIDS related, 217 SNAEs) were observed. Rates of progression did not differ significantly between the two groups but the subgroup of those initiating ART with <200 CD4 cells/µL had significantly higher risk of progression after baseline, compared to those in the "High CD4" group. CONCLUSIONS: Individuals starting ART with <200 cells/µL remain on increased risk even after reaching 500 CD4 cells/µL. These patients should be closely followed.

Brain abscess caused by Enterococcus faecalis following a dental procedure in a patient with hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is a disease characterized by arteriovenous malformations (AVMs). Brain abscess is a complication of HHT with AVMs. Literature provides evidence that Enterococcus faecalis can cause endodontic infections. We present the case of an HHT patient who developed brain abscess due to E. faecalis after a dental procedure.

Changes in Body Mass Index after Initiation of Antiretroviral Treatment: Differences by Class of Core Drug.

Recent research on antiretroviral treatment (ART) for HIV suggests that integrase strand transfer inhibitors (INSTIs) cause faster weight gain compared to other drug classes. Here, we investigated changes in body mass index (BMI) and obesity prevalence after treatment initiation and corresponding differences between drug classes. Data were derived from a large collaborative cohort in Greece. Included individuals were adults who started ART, in or after 2010, while previously ART naïve and achieved virologic response within the first year of ART. Data were analysed using mixed fractional polynomial models. INSTI regimens led to the more pronounced BMI increases, followed by boosted PI and NNRTI based regimens. Individuals with normal initial BMI are expected to gain 6 kg with an INSTI regimen compared to 4 kg with a boosted PI and less than 3 kg with a NNRTI regimen after four years of treatment. Prevalence of obesity was 5.7% at ART initiation and 12.2%, 14.2% and 18.1% after four years of treatment with NNRTIs, PIs, and INSTIs, respectively. Dolutegravir or Raltegravir were associated with marginally faster BMI increase compared to Elvitegravir. INSTIs are associated with faster weight gain. INSTIs' increased risk of treatment emergent obesity and, possibly, weight-related co-morbidities should be judged against their improved efficacy and tolerability but increased clinical attention is required.

Gastric syphilis: a systematic review of published cases of the last 50 years.

The authors conducted a systematic review of the English literature for cases of Gastric Syphilis (GS) in the last 50 years. The 34 studies which met selection criteria included 52 patients with GS. Of the reviewed patients, only 13% had a history of syphilis diagnosis and 46% had prior or concurrent clinical manifestations of the disease. Epigastric pain/fullness was the most common presenting symptom (92%) and epigastric tenderness being the most common sign. Gastric bleeding of variable intensity was documented in 35% of the cases. In the radiologic examinations, fibrotic narrowing and rigidity of the gastric wall was the most common finding (43%), followed by hypertrophic and irregular folds, while in endoscopy the most common lesion types were multiple ulcerations (48%), nodular mucosa, and erosions. The antrum was the most commonly affected area (56%). The majority of the patients received penicillin (83%) with a rapid resolution of their symptoms. Seventeen percent of the patients were treated surgically either due to a complication or due to strong suspicion of infiltrating tumor or lymphoma. The nonspecific clinical, radiologic, and pathologic characteristics of GS can establish it as a great imitator of other gastric diseases. GS should be considered in the differential diagnosis in patients at risk for sexually transmitted diseases who present with abdominal complaints and unusual endoscopic lesions and no other diagnosis is made, irrespective of the presence of H. pylori. The absence of primary or secondary luetic lesions should not deter one from considering GS.

Multicentric Castleman's disease in HIV infection: a systematic review of the literature.

The objective of this study is to systematically review the epidemiology and the clinical and virologic aspects of multicentric Castleman's disease in HIV-positive patients and to evaluate treatment strategies and outcome, especially in relation to HAART administration. The authors have conducted a systematic review of the English literature for all cases of newly diagnosed multicentric Castleman's disease in HIV-positive patients. The 25 studies which met the selection criteria included 84 HIV-positive patients with multicentric Castleman's disease (20 pre-HAART and 64 post-HAART era). Of them, the majority (90%) were men with 33 months median time from detection of HIV-positivity to multicentric Castleman's disease diagnosis in the HAART era. Fever and lymphadenopathy were the most common presenting symptoms and cytopenias, hypoalbuminemia, polyclonal hypergammaglobulinemia and raised C-reactive protein the most frequently revealed laboratory findings. Kaposi's sarcoma was present in 72% of the patients and respiratory system involvement in 34%. Although the majority of cases reported were positive for human herpesvirus-8, none of the reviewed patients was found to suffer from polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. Of the 48 patients on HAART, 64% were already on HAART at multicentric Castleman's disease diagnosis, having a better immunologic profile and a lower incidence of Kaposi's sarcoma than the 35% of patients who initiated HAART after multicentric Castleman's disease diagnosis. Nevertheless, the two groups did not have significantly different mortality rates (30 vs. 38%). At multicentric Castleman's disease diagnosis, a wide range of CD4 counts was recorded, suggesting that disease presentation could occur at any CD4 count. With regard to treatment, the study confirmed the high rates of response with rituximab (anti-CD20 monoclonal). Monochemotherapy seems to give short-lived responses, which require maintenance to be sustained. Polychemotherapy with CHOP has given long-term remission in a subset of patients. Other regimens used in the treatment of HIV-related multicentric Castleman's disease were antiviral agents, immunomodulatory agents, and thalidomide. The fatality rate among HIV-related multicentric Castleman's disease cases reviewed was 44%, significantly lower than that of HIV-negative individuals (65%), while median survival of the latter was 29 months longer than that of HIV-infected individuals. The fatality rate among pre-HAART patients was 75 vs. 29% among HAART patients. Infection, multiorgan failure, Kaposi's sarcoma, non-Hodgkin lymphoma and progressive multicentric Castleman's disease were the most often reported causes of death. In conclusion, multicentric Castleman's disease is a lymphoproliferative disorder with an increasing prevalence in HIV-infected individuals. Even though life expectancy in multicentric Castleman's disease seems to have significantly improved in the HAART era, it remains a disease with a poor prognosis and an increased incidence of non-Hodgkin lymphoma in the HIV-context.

Long-term evolution of CD4+ cell count in patients under combined antiretroviral therapy.

OBJECTIVE: Combined antiretroviral treatment (cART) results in profound immunologic improvement, but it is unclear whether CD4 cell counts return to levels similar to those of HIV-negative individuals. We explore long-term CD4 cell count evolution post-cART and its association with baseline levels, virologic suppression, pre-cART cumulative viremia and other factors. DESIGN: Data were derived from the AMACS. Included individuals were adults who started cART, at least 2003, while previously ART-naive. METHODS: Changes in CD4 cell counts were modeled through piecewise linear mixed models. RESULTS: A total of 3405 individuals were included. The majority was male (86.0%), homosexual (58.8%) with median (IQR) age at cART initiation 36 (31-44) years and a median (IQR) follow-up of 3.9 (2.0-6.9) years. Most persons (57%) starting cART with less than 200 cells/µl did not reach 600 cells/µl after 7 years of treatment. Those starting cART with 200-349 CD4 cells/µl could reach 600 cells/µl within less than 2 years of fully suppressive treatment. Probability of CD4 normalization (i.e. >800 cells/µl) after 7 years of suppressive treatment was 24 and 46% for those starting treatment with less than 200 or 200-349 CD4 cells/µl, respectively. Lower pre-cART cumulative viremia was associated with faster CD4 recovery. CD4 cell count increases after 4 years were either insignificant or very slow, irrespectively of baseline levels. CONCLUSION: cART initiation before CD4 cell count drops below 350 cells/µl is crucial for achieving normal CD4 levels. These findings underline the importance of timely diagnosis and cART initiation as the risk of both AIDS and non-AIDS-related morbidity/mortality remains increased in patients with incomplete CD4 recovery.

Lymphocutaneous nocardiosis in a kidney transplant patient successfully treated with tigecycline.

Cutaneous nocardiosis is an infrequent infection which has been increasingly reported in immunocompromised patients. Although trimethoprim-sulfamethoxazole is considered to be the agent of choice for treatment of nocardiosis, newer antimicrobials such as tigecycline have been proven to be effective in vitro, as well. We report the first case of primary cutaneous nocardiosis in a renal transplant recipient having corresponded well to treatment with tigecycline.

Long-term complete regression of nodal marginal zone lymphoma transformed into diffuse large B-cell lymphoma with highly active antiretroviral therapy alone in human immunodeficiency virus infection.

Since the introduction of combination antiretroviral therapy (cART), there has been a decrease in the incidence of non-Hodgkin lymphoma among the HIV-infected population and also significantly improved survival rates. We describe a remarkable case of a HIV-infected patient whose large B-cell lymphoma, most likely arising by transformation of a nodal marginal zone lymphoma, completely regressed with the use of cART alone. He remained disease-free for almost 3 years and he finally died from presumed flare up of his lymphoma. There are very few cases of spontaneous regression of lymphomas with cART alone in the HIV population. This is an extreme example of the significance of cART in improving survival in HIV-non-Hodgkin lymphoma and changing the face of the HIV epidemic in general.

Primary sternal osteomyelitis caused by Nocardia nova: case report and literature review.

A 51 year old woman without significant past medical history or risk factors for Nocardia infection developed primary Nocardia nova sternal osteomyelitis with mediastinal abscess, diagnosed with open biopsy. She required prolonged antibiotic therapy and had a favorable outcome. Primary sternal osteomyelitis develops in the absence of a contiguous focus of infection, as opposed to secondary sternal osteomyelitis, which is usually a complication of sternotomy. Staphylococcus aureus probably still is the most common cause of both forms of sternal osteomyelitis. Nocardia species invade humans usually through the respiratory tract and can cause a variety of localized infections through the hematogenous route. Pulmonary involvement may or may not coexist. Immunosuppressed patients are more prone to infection by Nocardia species, although cases involving seemingly immunocompetent patients are not rare. This is the first reported case in the English literature of primary sternal osteomyelitis due to Nocardia nova or any other Nocardia species.

Streptococcus pneumoniae septic arthritis complicating hip osteonecrosis in adults: case report and review of the literature.

A 42-year-old patient presented acutely with bacteremic pneumococcal pneumonia along with metastatic pneumococcal infection of the hip joint. Diagnostic evaluation revealed evidence of a pre-existing bilateral hip osteonecrosis. The osteonecrotic changes were attributed to chronic alcohol abuse and/or an old motor vehicle accident. Appropriate therapy was promptly instituted and the septic arthritis responded well, necessitating hip aspiration only once. A few months later, the patient had no permanent sequelae of the infection.

Primary sternal osteomyelitis caused by Nocardia nova: case report and literature review

A 51 year old woman without significant past medical history or risk factors for Nocardia infection developed primary Nocardia nova sternal osteomyelitis with mediastinal abscess, diagnosed with open biopsy. She required prolonged antibiotic therapy and had a favorable outcome. Primary sternal osteomyelitis develops in the absence of a contiguous focus of infection, as opposed to secondary sternal osteomyelitis, which is usually a complication of sternotomy. Staphylococcus aureus probably still is the most common cause of both forms of sternal osteomyelitis. Nocardia species invade humans usually through the respiratory tract and can cause a variety of localized infections through the hematogenous route. Pulmonary involvement may or may not coexist. Immunosuppressed patients are more prone to infection by Nocardia species, although cases involving seemingly immunocompetent patients are not rare. This is the first reported case in the English literature of primary sternal osteomyelitis due to Nocardia nova or any other Nocardia species.