[New opportunities for complex treatment of oropharyngeal candidiasis in HIV-infected patients in the later stages of the disease].

Treatment of recurrent oropharyngeal candidiasis (OPC) in HIV-infected patients is a serious clinical problem due to the emergence of resistant Candida strains, the risk of invasive disease, and high economic costs, which warrants the need for new treatment regimens. AIM: To improve the treatment regimen of OPC in the later stages of HIV infection by combining the complex herbal medicinal product Tonsilgon® N with fluconazole and evaluate the effectiveness of this combination. MATERIALS AND METHODS: A comparative randomized clinical study included 65 patients divided into observation and comparison groups, receiving fluconazole plus Tonsilgon® H and fluconazole monotherapy, respectively, for 7 days. On days 1 and 8, the severity of OPC clinical signs was assessed using a visual analog scale. The secretory immunoglobulin A in saliva was measured as a criterion for changing the level of local mucosal protection of the oral cavity and pharynx. CONCLUSION: This treatment regimen for oropharyngeal candidiasis in patients with HIV infection in the later stages of the disease (IVB-IVC) with fluconazole and Tonsilgon® N is effective, which is confirmed by a significantly more pronounced regression of clinical signs (pM-U<0.01), as well as an increase in the level of secretory immunoglobulin A in the oral fluid (from 0.62±0.33 g/L to 0.81±0.18 g/L; p<0.05).

Factors affecting uptake and completion of isoniazid preventive therapy among HIV-infected children at a national referral hospital, Kenya: a mixed quantitative and qualitative study.

BACKGROUND: Tuberculosis (TB) is the most common opportunistic infection and the leading cause of death in people living with HIV (PLHIV). HIV-infected children are at a higher risk of TB infection and disease compared to those without HIV. Isoniazid preventive therapy (IPT) is an effective intervention in preventing progression of latent TB infection to active TB. The World Health Organization (WHO) currently recommends that all children aged > 12 months and adults living with HIV in whom active TB has been excluded should receive a 6-months course of IPT as part of a comprehensive package of HIV care. Despite this recommendation, the uptake of IPT among PLHIV has been suboptimal globally. This study sought to determine the factors affecting IPT uptake and completion among HIV-infected children in a large HIV care centre in Nairobi, Kenya. METHOD: This was a cross-sectional mixed methods study comprising of quantitative and qualitative study designs. Medical records of 225 HIV-infected children aged 1 to < 10 years, in care in the Kenyatta National Hospital Comprehensive Care Centre (KNH CCC) were retrospectively reviewed, and 8 purposively selected healthcare providers and 18 consecutively selected caregivers of children were interviewed. RESULTS: IPT uptake among CLHIV in care in the KNH CCC was 68% (152/225) while the treatment completion rate was 82% (94/115). IPT-related health education and counselling were the main facilitators of IPT uptake and completion, while fear of adverse drug reaction, pill burden and lack of an integrated monitoring and evaluation system for IPT were the major barriers. CONCLUSION: The IPT uptake in this study was low and fell short of the set global target of > 90%. The completion rate was however acceptable. There is an urgent need to address the identified barriers.

Pharmacokinetic study of two different rifabutin doses co-administered with lopinavir/ritonavir in African HIV and tuberculosis co-infected adult patients.

BACKGROUND: This study aimed to assess the pharmacokinetic profile of 150 mg rifabutin (RBT) taken every other day (every 48 h) versus 300 mg RBT taken every other day (E.O.D), both in combination with lopinavir/ritonavir (LPV/r), in adult patients with human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection. METHODS: This is a two-arm, open-label, pharmacokinetic, randomised study conducted in Burkina Faso between May 2013 and December 2015. Enrolled patients were randomised to receive either 150 mg RBT EOD (arm A, 9 subjects) or 300 mg RBT EOD (arm B, 7 subjects), both associated with LPV/r taken twice daily. RBT plasma concentrations were evaluated after 2 weeks of combined HIV and TB treatment. Samples were collected just before drug ingestion and at 1, 2, 3, 4, 6, 8, and 12 h after drug ingestion to measure plasma drug concentration using an HPLC-MS/MS assay. RESULTS: The Cmax and AUC0-12h medians in arm A (Cmax = 296 ng/mL, IQR: 205-45; AUC0-12h = 2528 ng.h/mL, IQR: 1684-2735) were lower than those in arm B (Cmax = 600 ng/mL, IQR: 403-717; AUC0-12h = 4042.5 ng.h/mL, IQR: 3469-5761), with a statistically significant difference in AUC0-12h (p = 0.044) but not in Cmax (p = 0.313). No significant differences were observed in Tmax (3 h versus 4 h). Five patients had a Cmax below the plasma therapeutic limit (< 300 ng/mL) in the 150 mg RBT arm, while the Cmax was above this threshold for all patients in the 300 mg RBT arm. Additionally, at 48 h after drug ingestion, all patients had a mycobacterial minimum inhibitory concentration (MIC) above the limit (> 64 ng/mL) in the 300 mg RBT arm, while 4/9 patients had such values in the 150 mg RBT arm. CONCLUSION: This study confirmed that the 150 mg dose of rifabutin ingested EOD in combination with LPV/r is inadequate and could lead to selection of rifamycin-resistant mycobacteria. TRIAL REGISTRATION: PACTR201310000629390, 28th October 2013.

Total mouth photodynamic therapy mediated by blue led and curcumin in individuals with AIDS.

OBJECTIVES: To test the effectiveness of an efficient therapeutic protocol for the total mouth antimicrobial photodynamic therapy (aPDT) mediated by 450 nm blue LED associated with curcumin in individuals with AIDS. METHODS: Patients were selected by exclusion criteria and randomly distributed in groups to test the effectiveness of antimicrobial aPDT with curcumin 0.75 mg/mL associated with the blue LED (67 mW/cm2, 20.1 J/cm2). Before and after the treatments, samples were collected from the saliva being processed in duplicate in selective culture media. The colonies were counted and the results obtained in log10 CFU/mL were statistically tested (T-paired statistical test, 5%). RESULTS: The log10 CFU/mL of Streptococcus spp., Staphylococcus spp., and total count of microorganisms showed statistically significant (p = 0.023; p = 0.001 and p = 0.017, respectively) reduction after treatment in patients with aPDT. CONCLUSION: aPDT was effective in reducing Streptococcusspp. in addition to reducing Staphylococcusspp., enterobacteria and the total count of microorganisms when considering the numbers of TCD4 and TCD8 lymphocytes. The aPDT in the studied protocol was able to control clinically important intraoral microorganisms for AIDS patients, both those with TCD4 lymphocytes above or below 25% of normal and those with TCD8 lymphocytes above 25% of normal.

Prevalence of Multi-Drug Resistant Tuberculosis among Tuberculosis Patients Attending Chest Clinics in Osun-State, Nigeria.

BACKGROUND: The development of multidrug-resistant tuberculosis (MDR-TB) poses a considerable threat to tuberculosis control programmes in Nigeria. There is an increase in the prevalence of MDR-TB worldwide both among new tuberculosis cases as well as previously-treated ones. There is also a rise in transmission of resistant strains due to an increase in MDR-TB patients largely due to the poor drug compliance and the impact of Human immunodeficiency virus infection. Therefore, we intend to determine the extent of MDR-TB among attendees of chest clinics in Osun-State, Nigeria. OBJECTIVES: The objective of this study was to determine the prevalence of MDR-TB among confirmed tuberculosis patients attending chest clinics in Osun-State, Nigeria. METHODS: This study was conducted among 207 attendees of chest clinics in Osun-State between June, 2015 and October 15, 2016. Sputum and blood samples of the participants were collected. GeneXpert test was carried out first on the samples for simultaneous identification of MTB and rifampicin resistance. Sputum samples were cultured on Lowenstein-Jensen (L-J) medium using N-acetyl-Lcysteine- sodium hydroxide (NALC-NaOH) decontamination method. Drug susceptibility testing (DST) to three first-line drugs was carried out using the proportion DST method. RESULTS: The prevalence of MTB was found to be 27.5% while the prevalence of MDR-TB from the fifty-seven isolates was 10.5%. Previously treated and new cases had a prevalence of 7.0% and 3.5% MDR-TB, respectively. Seventy (33.8%) participants were positive for HIV infection, out of which twenty-six (12.6%) had co-infection of tuberculosis and HIV. The mono-resistance rates of the three first-line drugs used were: 5.3% and 8.7% for ethambutol (EMB) and isoniazid (INH), respectively. No isolate had mono-resistance (0%) to rifampicin (RIF). CONCLUSION: This study observed the prevalence of 27.5% MTB and a prevalence of 10.5% MDR-TB among the MTB isolates. The prevalence of TB is high in Osun State. MDR-TB prevalence is higher compared with the national estimate of MDR-TB (5.1%) of 2017. Resistant TB is a threat to national tuberculosis control and it is recommended that all the facilities be equipped to cater to its diagnosis.

Risk factors for poor treatment outcomes of 2266 multidrug-resistant tuberculosis cases in Ho Chi Minh City: a retrospective study.

BACKGROUND: Multidrug resistant tuberculosis (MDR-TB) remains a serious public health problem with poor treatment outcomes. Predictors of poor outcomes vary in different regions. Vietnam is among the top 30 high burden of MDR-TB countries. We describe demographic characteristics and identify risk factors for poor outcome among patients with MDR-TB in Ho Chi Minh City (HCMC), the most populous city in Vietnam. METHODS: This retrospective study included 2266 patients who initiated MDR-TB treatment between 2011 and 2015 in HCMC. Treatment outcomes were available for 2240 patients. Data was collected from standardized paper-based treatment cards and electronic records. A Kruskal Wallis test was used to assess changes in median age and body mass index (BMI) over time, and a Wilcoxon test was used to compare the median BMI of patients with and without diabetes mellitus. Chi squared test was used to compare categorical variables. Multivariate logistic regression with multiple imputation for missing data was used to identify risk factors for poor outcomes. Statistical analysis was performed using R program. RESULTS: Among 2266 eligible cases, 60.2% had failed on a category I or II treatment regimen, 57.7% were underweight, 30.2% had diabetes mellitus and 9.6% were HIV positive. The notification rate increased 24.7% from 2011 to 2015. The treatment success rate was 73.3%. Risk factors for poor treatment outcome included HIV co-infection (adjusted odds ratio (aOR): 2.94), advanced age (aOR: 1.45 for every increase of 5 years for patients 60 years or older), having history of MDR-TB treatment (aOR: 5.53), sputum smear grade scanty or 1+ (aOR: 1.47), smear grade 2+ or 3+ (aOR: 2.06), low BMI (aOR: 0.83 for every increase of 1 kg/m2 of BMI for patients with BMI < 21). CONCLUSION: The number of patients diagnosed with MDR-TB in HCMC increased by almost a quarter between 2011 and 2015. Patients with HIV, high smear grade, malnutrition or a history of previous MDR-TB treatment are at greatest risk of poor treatment outcome.

Unusual presentation of a disseminated oral HPV infection after combined antiretroviral therapy initiation.

HPV clinical manifestations have their characteristics modified by the use of combined antiretroviral therapy (cART), although its incidence is unaffected by cART. We report an unusual presentation of oral HPV infection and discuss an effective treatment for disseminated HPV lesions. A 52-year-old male of Asian-origin, HIV-seropositive, presented with extensive nodular lesions throughout the oral mucosa extending to the oropharyngeal region. Biopsy followed by histopathological examination and HPV genotyping were performed. The treatment was initiated with topical application of podophyllin and trichloroacetic acid. HPV lesions in oral mucosa are generally easy to handle. Extensive lesions can make it difficult to choose an effective treatment that meets the patient's particularities and medication availability.

Factors associated with isoniazid resistant tuberculosis among human immunodeficiency virus positive patients in Swaziland: a case-control study.

BACKGROUND: Isoniazid resistant tuberculosis is the most prevalent type of resistance in Swaziland and over two-thirds of the isoniazid resistant tuberculosis patients are tuberculosis and human immunodeficiency virus co-infected. The study aimed to determine risk factors associated with isoniazid resistant tuberculosis among human immunodeficiency virus positive patients in Swaziland. METHODS: This was a case-control study conducted in nine healthcare facilities across Swaziland. Cases were patients with isoniazid resistant tuberculosis (including 78 patients with isoniazid mono-resistant tuberculosis, 42 with polydrug-resistant tuberculosis, and 77 with multidrug-resistant tuberculosis). Controls were presumed drug-susceptible tuberculosis patients (n = 203). Multinomial logistic regression was used to determine related factors. RESULTS: The median time lag from diagnosis to tuberculosis treatment initiation was 50 days for isoniazid mono or poly drug-resistant tuberculosis, 17 days for multidrug-resistant tuberculosis compared to 1 day for drug-susceptible tuberculosis patients. History of previous tuberculosis treatment was positively associated with either isoniazid mono or poly drug-resistant tuberculosis (OR = 7.91, 95% CI: 4.14-15.11) and multidrug-resistant tuberculosis (OR = 12.20, 95% CI: 6.07-24.54). Isoniazid mono or poly resistant tuberculosis patients were more likely to be from rural areas (OR = 2.05, 95% CI: 1.23-3.32) and current heavy alcohol drinkers compared to the drug-susceptible tuberculosis group. Multi drug-resistant tuberculosis patients were more likely to be non-adherent to tuberculosis treatment compared to drug-susceptible tuberculosis group (OR = 3.01, 95% CI: 1.56-5.82). CONCLUSION: To prevent and control isoniazid resistant tuberculosis among HIV-positive patients in Swaziland, the tuberculosis program should strengthen the use of rapid diagnostic tests, detect resistance early, promptly initiate supervised tuberculosis treatment and decentralize quality tuberculosis services to the rural areas. Adherence to tuberculosis treatment should be improved.

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.

Patient and treatment pathways for toxoplasmosis in the United States: data analysis of the Vizient Health Systems Data from 2011 to 2017.

Toxoplasmosis causes substantial morbidity and mortality in the United States (US). Clinical manifestations to toxoplasmosis vary and there is limited information on incidence or treatment patterns in the US. Treatment pathways for pyrimethamine-based regimens and trimethoprim-sulfamethoxazole (TMP-SMX) for toxoplasmosis hospitalizations were investigated using the Vizient Health Systems inpatient and outpatient data. Between January 1st, 2011 and December 31st, 2017, 10,273 hospital visits from 4,736 unique patients received a primary or secondary ICD-9/ICD-10 diagnosis for toxoplasmosis. The projected annual hospital visits with a diagnosis of toxoplasmosis was 68,821, corresponding to a total annual incidence of 9,832 comprising ocular toxoplasmosis of 2,169, toxoplasmic encephalitis of 1,399, unspecified toxoplasmosis of 4,368, congenital toxoplasmosis of 381, multisystemic toxoplasmosis of 69 and other toxoplasmosis of 1,446. Only 16.3% of the study population received treatment with pyrimethamine-based regimens or TMP-SMX. Pyrimethamine-based regimens were used significantly more often than TMP-SMX in toxoplasmic encephalitis (88.7% vs 79.6%, p = 0.01), other toxoplasmosis (85.0% vs 79.2%, p = 0.04), and unspecified toxoplasmosis (87.6% vs 77.9%, p = 0.03) in hospitals with 300 beds or more. A significantly higher percentage of visits with TMP-SMX as first-line treatment switched to pyrimethamine-based regimens compared to visits initiated on pyrimethamine-based treatments (26.7% vs 4.1%, p < .001). Ocular toxoplasmosis patients receiving pyrimethamine-based therapy were more likely to be discharged home compared to TMP-SMC at rates of 72.4% and 55.2%, respectively. Our analysis of commercial insurance records suggest toxoplasmosis is undertreated. Overall, pyrimethamine-based regimens are favored over TMP-SMX, have higher rates of discharge home, and have lower switch rates.

Experimental Models of Short Courses of Liposomal Amphotericin B for Induction Therapy for Cryptococcal Meningitis.

Cryptococcal meningoencephalitis is a rapidly lethal infection in immunocompromised patients. Induction regimens are usually administered for 2 weeks. The shortest effective period of induction therapy with liposomal amphotericin B (LAMB) is unknown. The pharmacodynamics of LAMB were studied in murine and rabbit models of cryptococcal meningoencephalitis. The concentrations of LAMB in the plasma and brains of mice were measured using high-performance liquid chromatography (HPLC). Histopathological changes were determined. The penetration of LAMB into the brain was determined by immunohistochemistry using an antibody directed to amphotericin B. A dose-dependent decline in fungal burden was observed in the brains of mice, with near-maximal efficacy achieved with LAMB at 10 to 20 mg/kg/day. The terminal elimination half-life in the brain was 133 h. The pharmacodynamics of a single dose of 20 mg/kg was the same as that of 20 mg/kg/day administered for 2 weeks. Changes in quantitative counts were reflected by histopathological changes in the brain. Three doses of LAMB at 5 mg/kg/day in rabbits were required to achieve fungicidal activity in cerebrospinal fluid (cumulative area under the concentration-time curve, 2,500 mg · h/liter). Amphotericin B was visible in the intra- and perivascular spaces, the leptomeninges, and the choroid plexus. The prolonged mean residence time of amphotericin B in the brain suggests that abbreviated induction regimens of LAMB are possible for cryptococcal meningoencephalitis.

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.

Integrated therapy for HIV and cryptococcosis.

Cryptococcosis has been one of the most common opportunistic infections and causes of mortality among HIV-infected patients, especially in resource-limited countries. Cryptococcal meningitis is the most common form of cryptococcosis. Laboratory diagnosis of cryptococcosis includes direct microscopic examination, isolation of Cryptococcus from a clinical specimen, and detection of cryptococcal antigen. Without appropriate treatment, cryptococcosis is fatal. Early diagnosis and treatment is the key to treatment success. Treatment of cryptococcosis consists of three main aspects: antifungal therapy, intracranial pressure management for cryptococcal meningitis, and restoration of immune function with antiretroviral therapy (ART). Optimal integration of these three aspects is crucial to achieving successful treatment and reducing the mortality. Antifungal therapy consists of three phases: induction, consolidation, and maintenance. A combination of two drugs, i.e. amphotericin B plus flucytosine or fluconazole, is preferred in the induction phase. Fluconazole monotherapy is recommended during consolidation and maintenance phases. In cryptococcal meningitis, intracranial pressure rises along with CSF fungal burden and is associated with morbidity and mortality. Aggressive control of intracranial pressure should be done. Management options include therapeutic lumbar puncture, lumbar drain insertion, ventriculostomy, or ventriculoperitoneal shunt. Medical treatment such as corticosteroids, mannitol, and acetazolamide are ineffective and should not be used. ART has proven to have a great impact on survival rates among HIV-infected patients with cryptococcosis. The time to start ART in HIV-infected patients with cryptococcosis has to be deferred until 5 weeks after the start of antifungal therapy. In general, any effective ART regimen is acceptable. Potential drug interactions between antiretroviral agents and amphotericin B, flucytosine, and fluconazole are minimal. Of most potential clinical relevance is the concomitant use of fluconazole and nevirapine. Concomitant use of these two drugs should be cautious, and patients should be monitored closely for nevirapine-associated adverse events, including hepatotoxicity. Overlapping toxicities of antifungal and antiretroviral drugs and immune reconstitution inflammatory syndrome are not uncommon. Early recognition and appropriate management of these consequences can reinforce the successful integrated therapy in HIV-infected patients with cryptococcosis.

Oral mycoses and other opportunistic infections in HIV: therapy and emerging problems - a workshop report.

Oral mycoses and other opportunistic infections are recognized features of HIV infection even after four decades of the epidemic. The therapeutic options, challenges of therapy, and evolving patterns of opportunistic infections were evaluated by the workshop. It was observed that high Candida counts and infection are still more prevalent in HIV-positive individuals even in the era of antiretroviral therapy. Furthermore, one or more non-Candida albicans are present in some HIV-positive individuals. While Candida species are more virulent in HIV infection, similar virulence may be present in other states of immunosuppression. Consequently, the interplay between host factors and virulence ultimately determines the clinical outcomes. Adverse clinical outcomes such as candidemia and other deep fungal infections are on the increase in HIV infection. Disseminated histoplasmosis and penicilliosis have been reported, especially with low CD4 counts. Even with advances in antifungal therapy, mortality and morbidity from deep fungal infections have not changed significantly. In addition, long-term exposure to common antifungal drugs such as fluconazole has led to the development of antifungal resistance in 6% to 36%. Development of new antifungal therapeutic agents and the use of alternative therapies may offer breakthrough. In addition, effective strategies to enhance the host immune status are being explored.

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.

Reversing Gut Damage in HIV Infection: Using Non-Human Primate Models to Instruct Clinical Research.

Antiretroviral therapy (ART) has led to dramatic improvements in the lives of HIV-infected persons. However, residual immune activation, which persists despite ART, is associated with increased risk of non-AIDS morbidities. Accumulating evidence shows that disruption of the gut mucosal epithelium during SIV/HIV infections allows translocation of microbial products into the circulation, triggering immune activation. This disruption is due to immune, structural and microbial alterations. In this review, we highlighted the key findings of gut mucosa studies of SIV-infected macaques and HIV-infected humans that have revealed virus-induced changes of intestinal CD4, CD8 T cells, innate lymphoid cells, myeloid cells, and of the local cytokine/chemokine network in addition to epithelial injuries. We review the interplay between the host immune response and the intestinal microbiota, which also impacts disease progression. Collectively, these studies have instructed clinical research on early ART initiation, modifiers of microbiota composition, and recombinant cytokines for restoring gut barrier integrity.

Response to therapy in patients with cryptococcosis and AIDS: association with in vitro susceptibility to fluconazole / Respuesta al tratamiento en pacientes con criptococosis y sida: relación con la sensibilidad in vitro al fluconazol

Background. The implications of the Cryptococcus neoformans resistance to fluconazole on patient therapy have not been fully elucidated due to the discordant results found in published studies. Aims. To establish the influence of C. neoformans resistance to fluconazole in the therapy of individuals with cryptococcosis and AIDS. Methods. This study retrospectively compared the clinical course of patients with cryptococcosis according to the level of fluconazole resistance of their C. neoformans isolates. Results. This study included 71 episodes of cryptococcosis, defined as those isolates of C. neoformans obtained from patients with mycosis, of which 36 isolates were sensitive to fluconazole, 20 susceptible dose-dependent (SDD), and 15 were resistant. There were 5 treatment failures in the consolidation phase; two occurred in patients who had a susceptible strain, 2 in patients who had SDD strains, and one in a patient who had a resistant strain. During the maintenance treatment, relapses occurred in 4 of 33 patients (12%), seen during the follow-up period, none of which occurred in the group with resistant isolates. There were no significant differences in survival time free of treatment failure (p = 0.65) or survival time free of failure or relapse (p = 0.38). These results were not affected when tested in a Cox model that included age, CD4T lymphocyte counts, and use of antiretroviral therapy. Conclusions. In HIV patients with cryptococcosis, the resistance of C. neoformans appeared not to increase the risk of failure or relapse during treatment (AU)

Antecedentes. Las implicaciones de la resistencia de Cryptococcus neoformans al fluconazol en el tratamiento de pacientes infectados con esta levadura no han sido completamente definidas debido a hallazgos discordantes obtenidos previamente. Objetivos. Dilucidar la influencia de la resistencia de C. neoformans al fluconazol en el tratamiento de los pacientes con criptococosis y sida. Métodos. En este estudio se compara retrospectivamente la evolución clínica de los pacientes con criptococosis según el grado de resistencia al fluconazol de los aislamientos de C. neoformans obtenidos de ellos. Resultados. Se incluyeron 71 episodios de criptococosis definidos por el aislamiento de C. neoformans de pacientes con la micosis, que se distribuyeron de la siguiente manera: 36 aislamientos fueron sensibles, 20 sensibles dosis-dependiente y 15 resistentes. En la fase de consolidación, cinco fallos en el proceso de tratamiento tuvieron lugar: dos en pacientes con aislamientos sensibles, dos en pacientes con aislamientos dosis-dependiente y uno en un paciente con un aislamiento resistente. Durante la fase de mantenimiento se presentaron 4 recurrencias en los 33 pacientes que tuvieron seguimiento (12%), ninguna de las cuales ocurrió en el grupo con aislamientos resistentes. No se encontraron diferencias estadísticamente significativas en el tiempo de supervivencia de los casos sin fallo terapéutico (p = 0.65) o en el tiempo de supervivencia de los casos sin fallo terapéutico o recaída (p = 0.38). Estos resultados no se modificaron cuando fueron evaluados en un modelo de regresión de Cox en el que se incluyeron la edad, el conteo de linfocitos T CD4 y el uso de terapia antirretroviral. Conclusiones. En pacientes con VIH y criptococosis la resistencia de C. neoformans a fluconazol parece no incrementar el riesgo de fallo terapéutico o recaída (AU)

Response to therapy in patients with cryptococcosis and AIDS: Association with in vitro susceptibility to fluconazole.

BACKGROUND: The implications of the Cryptococcus neoformans resistance to fluconazole on patient therapy have not been fully elucidated due to the discordant results found in published studies. AIMS: To establish the influence of C. neoformans resistance to fluconazole in the therapy of individuals with cryptococcosis and AIDS. METHODS: This study retrospectively compared the clinical course of patients with cryptococcosis according to the level of fluconazole resistance of their C. neoformans isolates. RESULTS: This study included 71 episodes of cryptococcosis, defined as those isolates of C. neoformans obtained from patients with mycosis, of which 36 isolates were sensitive to fluconazole, 20 susceptible dose-dependent (SDD), and 15 were resistant. There were 5 treatment failures in the consolidation phase; two occurred in patients who had a susceptible strain, 2 in patients who had SDD strains, and one in a patient who had a resistant strain. During the maintenance treatment, relapses occurred in 4 of 33 patients (12%), seen during the follow-up period, none of which occurred in the group with resistant isolates. There were no significant differences in survival time free of treatment failure (p=0.65) or survival time free of failure or relapse (p=0.38). These results were not affected when tested in a Cox model that included age, CD4T lymphocyte counts, and use of antiretroviral therapy. CONCLUSIONS: In HIV patients with cryptococcosis, the resistance of C. neoformans appeared not to increase the risk of failure or relapse during treatment.

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.

Ethnobotanical study of indigenous knowledge on medicinal and nutritious plants used to manage opportunistic infections associated with HIV/AIDS in western Uganda.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional medicine plays an important role in the daily lives of the people of Uganda to treat a wide range of health problems. Our study presents results of an ethnobotanical inventory conducted to identify and document medicinal and nutritional plants used in the management of opportunistic infections associated with human immunodeficiency virus / acquired immunodeficiency syndrome (HIV/AIDS), the plant parts used, preparation and administration methods of herbal remedies. MATERIALS AND METHODS: We performed semi-structured interviews with 79 respondents (women 78%, men 22%), who included specialists in medicinal plants (such as traditional birth attendants and herbalists) and non specialists with general knowledge of plant use. Respondents answered a semi-structured questionnaire regarding their knowledge of plants and general treatment practices including management of HIV/AIDS opportunistic infections. The reported plants were collected and identified. Data were analyzed using factor informant consensus and fidelity level to determine homogeneity of informants׳ knowledge on medicinal and nutritional plants suitable for different ailment categories and the most preferred plant species used to treat each ailment category in the study areas. RESULTS: The study revealed 148 plant species belonging to 54 families, most of which were herbs (50.7%). Leaves (61.6%) were the most frequently used parts in remedy preparations which were mainly administered orally (72%). The majority of plants (62%) were harvested from wild habitats. The most important species according to fidelity values are Hibiscus sabdariffa L. for anaemia, Mangifera indica L. for cough, Zehneria scabra (L. F.) Sond. for skin infections, Rhus natalensis Bernh.ex.Krauss for diarrhoea and Tarenna pavettoides (Harv.) Sim for appetite boosting. The factor informant consensus highlighted the agreement in the use of plants and showed that the respiratory infections category had the greatest agreement (0.60). Family Asteraceae accounted for 15% of the total species recorded. Sixty plant species (40%) of the plants provide nutritional support. CONCLUSION: The study revealed that folk medicine is still widely practised. Fidelity level values indicate that these plants are the most preferred species for particular ailments. The high consensus value (0.6) indicated that there was high agreement in the use of plants for respiratory ailments among others. These preferred plant species could be prioritized for conservation and subjected to chemical screening to ascertain their pharmacological activities.