Integrating HCV testing with HIV programs improves hepatitis C outcomes in people who inject drugs: A cluster-randomized trial.

BACKGROUND & AIMS: There have been calls to integrate HCV testing into existing services, including harm reduction and HIV prevention and treatment, but there are few empirical trials to date. We evaluated the impact of integrating HCV testing/education into integrated care centers (ICCs) delivering HIV services to people who inject drugs (PWID) across India, using a cluster-randomized trial. METHODS: We compared ICCs with usual care in the PWID stratum (12 sites) of a 22-site cluster-randomized trial. In 6 sites, ICCs delivering HIV testing, harm reduction, other preventive services and linkage to HIV treatment were scaled from opioid agonist therapy centers and operated for 2 years. On-site rapid HCV antibody testing was integrated after 1 year. To assess impact, we conducted baseline and evaluation surveys using respondent-driven sampling (RDS) across the 12 sites (n = 11,993 recruited at baseline; n = 11,721 recruited at evaluation). The primary outcome was population-level self-reported HCV testing history. RESULTS: At evaluation, HCV antibody prevalence ranged from 7.2-76.6%. Across 6 ICCs, 5,263 ICC clients underwent HCV testing, of whom 2,278 were newly diagnosed. At evaluation, PWID in ICC clusters were 4-fold more likely to report being tested for HCV than in usual care clusters, adjusting for baseline testing (adjusted prevalence ratio [aPR] 3.69; 95% CI 1.34-10.2). PWID in ICC clusters were also 7-fold more likely to be aware of their HCV status (aPR 7.11; 95% CI 1.14-44.3) and significantly more likely to initiate treatment (aPR 9.86; 95% CI 1.52-63.8). CONCLUSIONS: We provide among the first empirical data supporting the integration of HCV testing into HIV/harm reduction services. To achieve elimination targets, programs will need to scale-up such venues to deliver comprehensive HCV services. CLINICALTRIALS. GOV IDENTIFIER: NCT01686750. LAY SUMMARY: Delivering hepatitis C virus (HCV) testing to people who inject drugs (PWID) in places where they also have access to HIV prevention and treatment services is an effective way to improve uptake of HCV testing among communities of PWID. To achieve the World Health Organization's ambitious elimination targets, integrated programs will need to be scaled up to deliver comprehensive HCV services.

Psoriasis in HIV infection: an update.

Psoriasis is a prevalent systemic immune-mediated disease with cutaneous manifestations. In HIV-infected patients, psoriasis may have a higher incidence, present atypical and more exuberant clinical features, and is frequently recalcitrant to treatment. Despite this aggravated severity, treatment options for psoriasis in HIV-infected individuals remain limited due to the risk of fatal immunosuppression associated with both classical immunosuppressants and new biological drugs. Notwithstanding, drug therapy in psoriasis has been undergoing major advances for the last few years, with novel drugs approved, which could significantly add to the management of HIV-infected patients. It is therefore our aim to present a review of the available literature to highlight the updated evidence on psoriasis in HIV-infected individuals, particularly in regards to its epidemiology, proposed pathophysiology, clinical presentation, currently available therapeutic options, and future perspectives.

Efficacy of vitamin D3 supplementation in reducing incidence of pulmonary tuberculosis and mortality among HIV-infected Tanzanian adults initiating antiretroviral therapy: study protocol for a randomized controlled trial.

BACKGROUND: HIV-infected adults initiating antiretroviral therapy (ART) in sub-Saharan Africa continue to experience high rates of morbidity and mortality during the initial months of treatment. Observational studies in high-income and resource-limited settings indicate that HIV-infected adults with low vitamin D levels may be at increased risk of mortality, HIV disease progression, and incidence of pulmonary tuberculosis (TB). As a result, vitamin D3 supplementation may improve survival and treatment outcomes for HIV-infected adults initiating ART. METHODS/DESIGN: The Trial of Vitamins-4 (ToV4) is an individually randomized, double-blind, placebo-controlled trial of vitamin D3 (cholecalciferol) supplementation conducted among 4000 HIV-infected adults with low vitamin D levels [25-hydroxyvitamin D (25(OH)D) <30 ng/mL] initiating ART in Dar es Salaam, Tanzania. The two primary aims of the trial are to determine the effect of a vitamin D3 supplementation regimen on incidence of (1) mortality and (2) pulmonary TB as compared to a matching placebo regimen. The primary safety outcome of the study is incident hypercalcemia. The investigational vitamin D3 regimen consists of oral supplements containing 50,000 IU vitamin D3 taken under direct observation at randomization and once a week for 3 weeks (four doses) followed by daily oral supplements containing 2000 IU vitamin D3 taken at home from the fourth week until trial discharge at 1 year post ART initiation. Trial participants are followed up at weekly clinic visits during the first month of ART and at monthly clinic visits thereafter until trial discharge at 1 year post ART initiation. Secondary aims of the trial are to examine the effect of the vitamin D3 regimen on CD4 T cell reconstitution, incidence of non-TB comorbidities, body mass index (BMI), depression and anxiety, physical activity, bone health, and immunologic biomarkers. DISCUSSION: The ToV4 will provide causal evidence on the effect of vitamin D3 supplementation on incidence of pulmonary TB and mortality among HIV-infected Tanzanian adults initiating ART. The trial will also give insight to whether vitamin D3 supplementation trials for the prevention of pulmonary TB should be pursued in HIV-uninfected populations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01798680 . Registered on 21 February 2013.

Imiquimod 5% tópico como terapia alternativa en carcinoma basocelular periocular en 2 pacientes con contraindicación quirúrgica / Topical imiquimod 5% as an alternative therapy in periocular basal cell carcinoma in two patients with surgical contraindication

CASO CLÍNICOS: Presentamos los casos de dos pacientes con carcinoma basocelular periocular palpebral, que recibieron imiquimod tópico al 5%, con buena respuesta. Ambos presentaban un estado funcional que desaconsejaba el tratamiento quirúrgico. CONCLUSIÓN: La crema de imiquimod al 5% ha demostrado ser una alternativa eficaz al tratamiento quirúrgico de tumores basocelulares perioculares, especialmente en aquellos casos en los que la cirugía no es posible

CLINICAL CASE: The cases are presented of two patients with periocular basal cell carcinoma of the eyelid who received topical imiquimod 5%, with a good response. Both had a functional state that contraindicated surgical treatment. CONCLUSION: Imiquimod cream 5% was shown to be an effective alternative to surgical treatment of periocular basal cell carcinoma, especially in those cases where surgery is not possible

Recent advances in AIDS-related cryptococcal meningitis treatment with an emphasis on resource limited settings.

INTRODUCTION: Recent advances in the treatment and prevention of cryptococcal meningitis have the potential to decrease AIDS-related deaths. Areas covered: Targeted screening for asymptomatic cryptococcal antigenemia in persons with AIDS is a cost effective method for reducing early mortality in patients on antiretroviral therapy. For persons with symptomatic cryptococcal meningitis, optimal initial management with amphotericin and flucytosine improves survival compared to alternative therapies; however, amphotsericin is difficult to administer and flucytosine has not been available in middle or low income countries, where cryptococcal meningitis is most prevalent. Expert commentary: Improved care for cryptococcal meningitis patients in resource-limited settings is possible, and new treatment possibilities are emerging.

Pneumocystis jirovecii Pneumonia in Human Immunodeficiency Virus Infection.

The presentation of Pneumocystis pneumonia (PCP) in previously healthy men having sex with men (MSM) in San Francisco and New York City in 1981 heralded the beginning of the human immunodeficiency virus (HIV) pandemic. Despite a decreasing incidence of PCP among patients with HIV/AIDS (acquired immunodeficiency syndrome) since the advent of combination antiretroviral therapy in the mid-1990s, PCP remains one of the most common AIDS-defining opportunistic infections in the United States and Western Europe. Newer molecular diagnostic tests in conjunction with standard immunofluorescent or colorimetric tests have allowed for more rapid and accurate diagnosis. Although several effective oral and intravenous therapies exist to treat PCP, mortality rates in HIV-infected individuals remain unacceptably high, especially in those with advanced AIDS. The identification of specific mutations in Pneumocystis genes targeted by trimethoprim-sulfamethoxazole has raised concerns about the development of resistance to the drug of choice and may ultimately lead to greater utilization of alternative therapies to treat PCP in the future.

Effect of highly active antiretroviral therapy on vaginal Candida spp. isolation in HIV-infected compared to HIV-uninfected women.

Vulvovaginal candidiasis (VVC) in HIV-infected women contributed to the impairment of their quality of life. The aim of this study was to evaluate the effect of highly active antiretroviral therapy (HAART) use on the vaginal Candida spp. isolation in HIV-infected compared to HIV-uninfected women. This cross-sectional study included 178 HIV-infected (HIV group) and 200 HIV-uninfected women (control) that were studied at the Specialized Assistance Service (SAE) for sexually transmitted diseases (STD)/AIDS of the city of Maringá, Brazil, from April 1 to October 30, 2011. The yeasts were isolated and identified by phenotypic and molecular methods. The in vitro antifungal susceptibility to fluconazole, itraconazole, nystatin and amphotericin B was tested by the reference microdilution method. Higher frequencies of total vaginal Candida spp. isolation were found in the HIV-infected group than in the control group. However, both groups showed a similar frequency of colonization and VVC. Although C. albicans was the most frequent and sensitive to azolics and polyenes in both HIV-infected and uninfected women, the emerging resistance of C. glabrata to amphotericin B in the HIV-infected women was observed. Although higher frequency of vaginal Candida spp. isolation had been observed in the HIV-infected than in HIV-uninfected women, colonization and VVC showed similar frequency in both groups, indicating that HAART appears to protect against vaginal colonization and VVC.

Cryptoccocal meningitis in Yaoundé (Cameroon) HIV infected patients: Diagnosis, frequency and Cryptococcus neoformans isolates susceptibility study to fluconazole.

Cryptococcal meningitis is a mycosis encountered especially in patients with Acquired Immunodeficiency Syndrome and is fatal in the absence of treatment. Information on epidemiology, diagnosis and susceptibility profile to antifungal drugs, are scarce in Cameroon. Authors evaluated the diagnosis possibilities of the cryptococcal meningitis in Cameroon, and studied the antifungal susceptibility of isolated strains to fluconazole, used as first line treatment of the disease in Cameroon. Between December 2009 and July 2011, 146 cerebrospinal fluids obtained from HIV patients with suspicion of meningitis were analysed. The diagnosis procedure involved macroscopic and cyto-chemical analysis, India ink test, culture on Sabouraud chloramphenicol medium and antigen latex agglutination test. Antifungal susceptibility testing of isolated strains to fluconazole was done by the E-test(®) method. The diagnosis of cryptococcal meningitis gave 28.08% positive cases. Among these patients, 80% were at stages III and IV and 20% at stage I of the HIV infection, according to the WHO previous classification. Cyto-chemical analysis showed current findings in the case of cryptococcal meningitis. India ink test and latex agglutination test exhibited very high sensitivity and specificity (>94%). Fluconazole antifungal susceptibility testing gave MICs lower than 32µg/mL to 92.7% of isolated strains and MICs greater than this value to 7.3% of isolates. These results showed that cryptococcal meningitis remains a real problem among HIV infected patients in Yaoundé. The emergence of fluconazole reduced susceptibility strains is worrying. Nevertheless, efficacy of rapid detection tests is interesting because this will help in rapid diagnosis and treatment of patients.

Diagnóstico bacteriológico de tuberculosis pulmonar mediante fibrobroncoscopía en pacientes con VIH / Bacteriological diagnosis of lung tuberculosis through bronchoscopy in HIV-infected patients

Tuberculosis can be lethal in HIV infected people. Lung is the organ most frequently involved, but clinical and radiological features are not typical of the disease. Diagnostic certification demands acid-fast bacillus microscopy and mycobacterial cultures on sputum. Some patients need bronchoscopy to obtain samples due to insufficient sputum. We reported a 9.1 percent diagnostic yield using bronchoscopy. Clinical suspicion before bronchoscopy had low positive predictive value of tuberculosis (10.8 percent). 47.8 percent of tuberculosis cases were not suspected before this procedure. Tuberculosis patients showed CD4 < 200 cells/mL (48.8 in average) and less use of ART (antiretroviral therapy). Cultures contributed to the diagnosis of 35 percent of tuberculosis cases but with a delay of 30 days. Induced sputum is a less costly alternative to bronchoscopy with a similar diagnostic yield.

La tuberculosis puede ser letal en pacientes infectados por VIH. El compromiso pulmonar es más frecuente en ellos y su cuadro clínico-radiológico no es típico de la enfermedad. El diagnóstico se confirma con baciloscopía y cultivo de Koch en esputo. Los pacientes sin esputo pueden requerir broncoscopía. Encontramos un rendimiento de 9,1 por ciento en diagnóstico de tuberculosis pulmonar por broncoscopía. La sospecha clínica de tuberculosis previa a broncoscopía tuvo bajo valor predictivo positivo (10,8 por ciento). 47,8 por ciento de los pacientes con Tuberculosis no fueron sospechados antes de la broncoscopía por lo que recomendamos este procedimiento en pacientes VIH con alteraciones radiológicas y síntomas respiratorios. Los casos de tuberculosis tenían CD4 < 200 células/mL (promedio 48,8) y menos uso de TAR: terapia antiretroviral. El 35 por ciento de los casos de tuberculosis se diagnosticó por cultivo (demora mínima de 30 días). El esputo inducido es una alternativa a la broncoscopía menos costosa y de similar rendimiento.

[Cryptococcal neuromeningitidis in HIV-infected patients in Bangui, in the era of antiretroviral treatment]. / La cryptococcose neuroméningée au cours de l'infection à VIH à Bangui, à l'ère du traitement antirétroviral.

The cryptococcal neuromeningitis is the most common fungal meningitis infections in the course of HIV/AIDS. This is the number two of opportunist infection of the central nervous system. The authors post the outcomes of a retrospective study conducted related to 122 cases of cryptococcal neuromeningitis observed over for four years ago, in Bangui in the Central African Republic, this at time when antiretroviral treatment has been avaible, corresponding to a prevalence of 6.5%. These infections very aften occur more in female folk, and to patients whose average age is 35 years old, ranging from 18 to 69 years old. The clinical symptoms often found had been headache (98,3.%), fever (95.0%), the impairing of the overall condition of the patient (86.7%) and neck stiffness (85.9%). It makes sense to notice that comorbidity case alowgwith tuberculosis, intestinal candidiasis, bacterial pneumonia and Kaposi's diseases were found out. The screening of the cerebrospinal fluid showed a sound cell count and even low count in 12.2% of cases. Direct examination of cerebrospinal fluid with India ink helps in diagnosis of 97.5% of cases, and the culture carried out from 74 patients was in any case positive. This culture allowed the diagnosis of three patients whose examination along side with India ink has been negative. The CD4 cell count was less than 100/mm(3) in 97.7% of cases. The rate of the fatality cases has been 66.4%, it has been badly impacted by a CD4 count <50/mm(3) and the lack of antiretroviral therapy. Despite the establishment of a national antiretroviral treatment program to do influence the frequency of opportunistic infections whose cryptococcal neuromeningitis, this condition is still present although it is declining. The clinical variability of this disease requires early diagnosis to avoid delayed treatment corollary of a very high mortality as we have observed.

Integrating clinical services for HIV, tuberculosis, and cryptococcal disease in the developing world: a step forward with 2 novel diagnostic tests.

The success of antiretroviral therapy (ART) programs in the developing world is limited by the lack of adequate diagnostic tests to screen for life-threatening opportunistic infections such as tuberculosis (TB) and cryptococcal disease. Furthermore, there is an increasing need for implementation research in measuring the effectiveness of currently available rapid diagnostic tests. The recently developed lateral flow assays for both cryptococcal disease and TB have the potential to improve care and greatly reduce the time to initiation of ART among individuals who need it the most. However, we caution that the data on feasibility and effectiveness of these assays are limited and such research agendas must be prioritized.

[Bacterial pneumonia in HIV-infected patients (excluding mycobacterial infection)]. / Pneumonies bactériennes chez les personnes infectées par le VIH (hors mycobactéries).

Respiratory infections are the most common complications in HIV patients, regardless of the degree of immunosuppression. Even though antiretroviral therapy has a protective effect on the risk of bacterial pneumonia, this still remains high (including those with CD(4)>500/mm(3)). The most frequently isolated bacteria are Streptococcus pneumoniae and Haemophilus influenzae. The clinical and radiological presentations of lower respiratory tract infections in HIV patients are quite variable. The clinical presentation is more severe and the radiological presentation is more atypical if the immunosuppression is severe. The first-line antibiotic therapy is an injectable third-generation cephalosporin (ceftriaxone or cefotaxime) or co-amoxiclav. Pneumococcal vaccination (as well as influenza vaccine) is recommended. Although rare, Nocardia spp. and Rhodococcus equi seem more common among AIDS patients.

PEPFAR support for the scaling up of collaborative TB/HIV activities.

The US President's Emergency Plan for AIDS Relief (PEPFAR) has supported a comprehensive package of care in which interventions to address HIV-related tuberculosis (TB) have received increased funding and support in recent years. PEPFAR's TB/HIV programming is based on the World Health Organization's 12-point policy for collaborative TB/HIV activities, which are integrated into PEPFAR annual guidance. PEPFAR implementing partners have provided crucial support to TB/HIV collaboration, and as a result, PEPFAR-supported countries in sub-Saharan Africa have made significant gains in HIV testing and counseling of TB patients and linkages to HIV care and treatment, intensified TB case finding, and TB infection control. PEPFAR's support of TB/HIV integration has also included significant investment in health systems, including improved laboratory services and educating and enlarging the workforce. The scale-up of antiretroviral therapy along with support of programs to increase HIV counseling and testing and improve linkage and retention in HIV care may have considerable impact on TB morbidity and mortality, if used synergistically with isoniazid preventive therapy, intensified case finding, and infection control. Issues to be addressed by future programming include accelerating implementation of isoniazid preventive therapy, increasing access and ensuring appropriate use of new TB diagnostics, supporting early initiation of antiretroviral therapy for HIV-infected TB patients, and strengthening systems to monitor and evaluate program implementation.

Histoplasmosis in HIV-positive patients in Ceará, Brazil: clinical-laboratory aspects and in vitro antifungal susceptibility of Histoplasma capsulatum isolates.

This study contains a descriptive analysis of histoplasmosis in AIDS patients between 2006 and 2010 in the state of Ceará, Brazil. Additionally, the in vitro susceptibility of Histoplasma capsulatum isolates obtained during this period was assessed. We report 208 cases of patients with histoplasmosis and AIDS, describing the epidemiological, clinical, laboratory and therapeutic aspects. The in vitro antifungal susceptibility test was carried out by the microdilution method, according to Clinical and Laboratory Standards Institute, with H. capsulatum in the filamentous and yeast phases, against the antifungals amphotericin B, fluconazole, itraconazole, voriconazole and caspofungin. In 38.9% of the cases, histoplasmosis was the first indicator of AIDS and in 85.8% of the patients the CD4 cell count was lower than 100 cells/mm(3). The lactate dehydrogenase levels were high in all the patients evaluated, with impairment of hepatic and renal function and evolution to death in 42.3% of the cases. The in vitro susceptibility profile demonstrated there was no antifungal resistance among the isolates evaluated. There was a significant increase in the number of histoplasmosis cases in HIV-positive patients during the period surveyed in the state of Ceará, northeastern Brazil, but no antifungal resistance among the recovered isolates of H. capsulatum.

Selenium levels in persons with HIV/tuberculosis in India, Madurai City.

BACKGROUND: Selenium plays a vital role in the immune status of the individual. The prospective observational study was conducted from September 2009 to March 2010. The aim of the present study is to investigate the association between serum selenium levels and pulmonary tuberculosis (PTB) patients with (n = 40) and without HIV (n = 40) in comparison to healthy controls (healthy family members; n = 20) who satisfied rigid selection criteria. METHODS: Standard methods were adopted to collect an early morning fasting blood sample for serum selenium concentrations, determined by atomic absorption spectrometry (AAS), and albumin, determined by the bro mocresol green method. RESULTS: The mean +/- SD for Body Mass Index (BMI), selenium, and albumin among the controls, HIV positive, and HIV negative patients were 19.6 +/- 0.6, 18 +/- 0.4 and 18.5 +/- 0.6 kg/m2; 113.1 +/- 4.1, 27.44 +/- 8, and 65.92 +/- 9, microg/dL; and 4.1 +/- 0.6, 2.9 +/- 0.4 and 3.6 +/- 0.7 g/dL, respectively. BMI, serum selenium, and albumin levels were found to be significantly lower (p < 0.004, p < 0.0321, and p < 0.002, respectively). CONCLUSIONS: Low serum selenium levels are associated with increased risk of pulmonary infection caused by mycobacteria.

Tuberculosis in HIV programmes in lower-income countries: practices and risk factors.

BACKGROUND: Tuberculosis (TB) is a common diagnosis in human immunodeficiency virus (HIV) infected patients on antiretroviral treatment (ART). OBJECTIVE: To describe TB-related practices in ART programmes in lower-income countries and identify risk factors for TB in the first year of ART. METHODS: Programme characteristics were assessed using standardised electronic questionnaire. Patient data from 2003 to 2008 were analysed and incidence rate ratios (IRRs) calculated using Poisson regression models. RESULTS: Fifteen ART programmes in 12 countries in Africa, South America and Asia were included. Chest X-ray, sputum microscopy and culture were available free of charge in respectively 13 (86.7%), 14 (93.3%) and eight (53.3%) programmes. Eight sites (53.3%) used directly observed treatment and five (33.3%) routinely administered isoniazid preventive treatment (IPT). A total of 19 413 patients aged ≥ 16 years contributed 13,227 person-years of follow-up; 1081 new TB events were diagnosed. Risk factors included CD4 cell count (>350 cells/µl vs. <25 cells/µl, adjusted IRR 0.46, 95%CI 0.33-0.64, P < 0.0001), sex (women vs. men, adjusted IRR 0.77, 95%CI 0.68-0.88, P = 0.0001) and use of IPT (IRR 0.24, 95%CI 0.19-0.31, P < 0.0001). CONCLUSIONS: Diagnostic capacity and practices vary widely across ART programmes. IPT prevented TB, but was used in few programmes. More efforts are needed to reduce the burden of TB in HIV co-infected patients in lower income countries.