RESUMEN

Extended Spectrum ß-Lactamases (ESBLs) confer resistance to third-generation cephalosporins and CTX-M types have emerged as the most prominent ESBLs worldwide. This study was designed to determine the prevalence of CTX-M positive ESBL-producing urinary E. coli isolates from HIV patients and to establish the association of multidrug resistance, phylogeny, and virulence profile with CTX-M production. A total of 57 ESBL producers identified among 76 E. coli strains isolated from HIV patients from South India were screened for bla CTX-M, AmpC production, multidrug resistance, and nine virulence associated genes (VAGs), fimH, pap, afa/dra, sfa/foc, iutA, fyuA, iroN, usp, and kpsMII. The majority (70.2%) of the ESBL producers harbored bla CTX-M and were AmpC coproducers. Among the CTX-M producers, 47.5% were found to be UPEC, 10% harbored as many as 7 VAGs, and 45% possessed kpsMII. Multidrug resistance (CIP(R)SXT(R)GEN(R)) was significantly more common among the CTX-M producers compared to the nonproducers (70% versus 41.2%). However, 71.4% of the multidrug resistant CTX-M producers exhibited susceptibility to nitrofurantoin thereby making it an effective alternative to cephalosporins/fluoroquinolones. The emergence of CTX-M-producing highly virulent, multidrug resistant uropathogenic E. coli is of significant public health concern in countries like India with a high burden of HIV/AIDS.

RESUMEN

BACKGROUND: The Revised National TB Control Program bases diagnosis of tuberculosis (TB) on sputum smear examination and response to a course of antibiotics, whereas World Health Organization recommends early chest radiography [chest x-ray (CXR)] for HIV-infected symptomatic patients. We evaluated the utility of initial CXR in the diagnostic algorithm for symptomatic HIV-infected patients with negative sputum smears. METHODS: HIV-infected ambulatory patients with cough or fever of ≥2 weeks and 3 sputum smears negative for acid-fast bacilli were enrolled in Chennai and Pune, India, between 2007 and 2009. After a CXR and 2 sputum cultures, a course of broad-spectrum antibiotics was given and patients were reviewed after 14 days. Sensitivity, specificity, positive and negative predictive values of symptoms, CXR, and various combinations for diagnosing pulmonary tuberculosis (PTB) were determined, using sputum culture as gold standard. RESULTS: Five hundred four patients (330 males; mean age: 35 years; median CD4: 175 cells per cubic millimeter) were enrolled. CXR had a sensitivity and specificity of 72% and 57%, respectively, with positive predictive value (PPV) of 21% and negative predictive value (NPV) of 93% to diagnose PTB. TB culture was positive in 49 of 235 patients (21%) with an abnormal initial CXR and 19 of 269 patients (7%) with a normal CXR (P < 0.001). Sensitivity and specificity of cough ≥2 weeks for predicting PTB was 97% and 6%, with PPV and NPV of 14% and 94%, respectively. CONCLUSIONS: Although moderately sensitive, basing a diagnosis of TB on initial CXR leads to overdiagnosis. An absence of weight loss had a high NPV, whereas none of the combinations had a good PPV. A rapid and accurate diagnostic test is required for HIV-infected chest symptomatic.

Asunto(s)

Infecciones por VIH/complicaciones , Pulmón/diagnóstico por imagen , Esputo/microbiología , Tuberculosis Pulmonar/diagnóstico por imagen , Tuberculosis Pulmonar/diagnóstico , Adulto , Algoritmos , Recuento de Linfocito CD4 , Femenino , Humanos , Masculino , Radiografía , Sensibilidad y Especificidad , Tuberculosis Pulmonar/complicaciones

RESUMEN

Extended-spectrum ß-lactamase (ESBL) production and quinolone resistance are often associated in enterobacteria. Prior exposure to 3G cephalosporins/quinolones accelerates the risk of resistance to both these groups of antibiotics. Hence, information on the antimicrobial resistance pattern of uropathogenic Escherichia coli (UPEC) isolates is important to better formulate the guidelines for the empirical therapy of urinary tract infection in the context of HIV/AIDS. The aim of this study was to determine the incidence of ESBL/AmpC and fluoroquinolone (FQ) resistance among urinary E. coli isolates and to establish the association of extraintestinal virulence and phylogenetic distribution with antibiotic resistance and host immunocompromisation. Accordingly, 118 urinary Escherichia coli isolates from HIV (n = 76) and non-HIV antenatal patients (n = 42) from Chennai, South India, were analysed for the presence of five virulence-associated genes (VAGs): pap, sfa/foc, afa/dra, iutA and kpsMII. Compared with the susceptible HIV isolates, the majority of the ESBL(+)AmpC(+)FQ(R) isolates harboured iutA (66.7%) and pap (40%). The FQ-resistant HIV isolates were significantly enriched for iutA (67.8%) and kpsMII (47.5%) and qualified as UPEC (54.2%), while a majority of the FQ-susceptible isolates from the non-HIV patients were found to harbour pap (48.4%), sfa/foc (41.9%) and kpsMII (48.4%) and were classified as UPEC (40.5%). We conclude that antibiotic-resistant (ESBL(+)AmpC(+)and/or FQ(R)) phylogroup D isolates with limited virulence are competent enough to establish infections in HIV patients, while among non-HIV patients, an array of virulence factors is essential for E. coli to overcome host defences irrespective of antibiotic resistance.

Asunto(s)

Proteínas Bacterianas/metabolismo , Farmacorresistencia Bacteriana/genética , Infecciones por VIH/complicaciones , Escherichia coli Uropatógena/efectos de los fármacos , Escherichia coli Uropatógena/patogenicidad , beta-Lactamasas/metabolismo , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Estudios de Casos y Controles , Regulación Bacteriana de la Expresión Génica , Regulación Enzimológica de la Expresión Génica , Genotipo , Humanos , Datos de Secuencia Molecular , Filogenia , Escherichia coli Uropatógena/enzimología , Escherichia coli Uropatógena/genética , Virulencia , beta-Lactamasas/genética

RESUMEN

BACKGROUND: The identification and management of first-line antiretroviral therapy (ART) failure is a key challenge for HIV programs in resource-limited settings. In 2008, the National AIDS Control Organisation, India piloted a national strategy to provide second-line ART. We assessed the National AIDS Control Organisation second-line ART evaluation algorithm. METHODS: Adult patients who had received 6 months or more of standard first-line ART were referred for second-line ART evaluation if they demonstrated CD4 decline to pre-ART values, CD4 drop to less than 50% of peak on-treatment value, failure to achieve CD4 greater than 100 c/mm(3), or development of a new World Health Organization Stage 3 or 4 AIDS-defining illness. Patients received HIV RNA testing, and those with HIV RNA 10,000 c/mL or greater qualified to switch to second-line ART. World Health Organization-defined clinical and CD4 criteria for ART failure were compared against virologic failure criteria. RESULTS: Between January and June 2008, 154 patients met criteria for evaluation. Of 122 (79%) patients who had HIV RNA testing, 87 (71%) had viral load 10,000 c/mL or greater and were recommended to start second-line ART, 29 (24%) had viral load less than 400 c/mL, and six (5%) had viral load between 400 and 10,000 c/mL. The positive predictive value of World Health Organization clinical/immunologic criteria to detect virologic failure was 71% (95% confidence interval, 63% to 79%). CONCLUSIONS: Second-line ART was initiated in the public sector in India using an approach combining clinical and immunologic evaluation with confirmation of virologic failure. Almost 25% of patients who met clinical/immunologic failure criteria demonstrated virologic suppression. Inclusion of targeted HIV RNA testing in the evaluation of treatment failure can prevent unnecessary switches to second-line ART.

Asunto(s)

Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH/efectos de los fármacos , ARN Viral/sangre , Adulto , Alquinos , Fármacos Anti-VIH/farmacología , Benzoxazinas/farmacología , Benzoxazinas/uso terapéutico , Recuento de Linfocito CD4 , Ciclopropanos , Femenino , VIH/fisiología , Infecciones por VIH/inmunología , Humanos , India , Lamivudine/farmacología , Lamivudine/uso terapéutico , Masculino , Persona de Mediana Edad , Nevirapina/farmacología , Nevirapina/uso terapéutico , Estavudina/farmacología , Estavudina/uso terapéutico , Insuficiencia del Tratamiento , Carga Viral , Zidovudina/farmacología , Zidovudina/uso terapéutico

RESUMEN

BACKGROUND: We aimed to analyse treatment outcomes of patients receiving first-line antiretroviral therapy (ART) through the national AIDS control programme of India. METHODS: Using routinely collected programme data, we analysed mortality, CD4 evolution and adherence outcomes over a 2-year period in 972 patients who received first-line ART between 1 October 2004 and 31 January 2005 at 3 government ART centres. Cox regression analysis was used to identify independent predictors of mortality. RESULTS: Of the 972 patients (median age 35 years, 66% men), 71% received the stavudinellamivudine/nevirapine regimen. The median CD4 count of enrolled patients was 119 cells/cmm (interquartile range [IQR] 50-200 cells/ cmm) at treatment initiation; 44% had baseline CD4 count <100 cells/cmm. Of the 927 patients for whom treatment outcomes were available, 71% were alive after 2 years of treatment. The median increase in CD4 count was 1 42 cells/ cmm (IQR 57-750 cells/cmm; n=616) at 6 months and 184 cells/cmm (IQR 102-299 cells/cmm; n=582) at 12 months after treatment. Over 2 years, 124 patients (13%) died; the majority of deaths (68%) occurred within the first 6 months of treatment. Those with baseline CD4 count <50 cells/cmm were significantly more likely to die (adjusted hazard ratio 2.5, 95% confidence interval 1.3-3.2) compared with patients who had baseline CD4 count >50 cells/cmm. Over the 2-year period, 323 patients (35%) missed picking up their monthly drugs at least once and 147 patients (16%) were lost to follow up. CONCLUSION: Survival rates of HIV-infected patients on first-line ART in India were comparable with those from other resource-limited countries. Most deaths occurred early and among patients who had advanced disease. Earlier initiation of HIV treatment and improving long term treatment adherence are key priorities for India's ART programme.

Asunto(s)

Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Fármacos Anti-VIH/uso terapéutico , Síndrome de Inmunodeficiencia Adquirida/inmunología , Adolescente , Adulto , Anciano , Fármacos Anti-VIH/efectos adversos , Recuento de Linfocito CD4 , Estudios de Cohortes , Femenino , Humanos , India , Masculino , Persona de Mediana Edad , Programas Nacionales de Salud , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Resultado del Tratamiento

Asunto(s)

Fármacos Anti-VIH/farmacocinética , Hidrocarburo de Aril Hidroxilasas/genética , Benzoxazinas/farmacocinética , Infecciones por VIH/tratamiento farmacológico , Nevirapina/farmacocinética , Oxidorreductasas N-Desmetilantes/genética , Plasma/química , Polimorfismo Genético , Adulto , Alquinos , Ciclopropanos , Citocromo P-450 CYP2B6 , Femenino , Frecuencia de los Genes , Humanos , India , Masculino , Persona de Mediana Edad , Mutación Puntual , Adulto Joven

RESUMEN

The dose of efavirenz during concomitant rifampin (RMP) administration is a matter of debate. We studied the influence of RMP coadministration on the steady-state pharmacokinetics of efavirenz in human immunodeficiency virus type 1 (HIV-1)-infected patients in South India. Fifty-seven HIV-tuberculosis (TB)-coinfected and 15 HIV-1-infected patients receiving combination antiretroviral therapy (CART) with an efavirenz (600 mg once daily)-containing regimen were recruited. HIV-TB-coinfected patients were receiving treatment with RMP-containing regimens. A complete pharmacokinetic study was conducted with 19 HIV-TB patients on two occasions (with and without RMP). Trough concentrations of efavirenz were measured in the remaining 38 patients during RMP coadministration. The 15 HIV-infected patients underwent complete pharmacokinetic sampling on one occasion. Plasma efavirenz was estimated by high-performance liquid chromatography, and genotyping of CYP2B6 G516T polymorphism was performed by sequencing. Peak and trough concentrations and exposure to efavirenz were significantly higher in TT than in GT and GG genotype patients (P < 0.001). Although RMP coadministration decreased the peak and trough concentrations and exposure to efavirenz by 17.8, 20.4, and 18.6%, respectively, the differences were not statistically significant. The trough concentration of efavirenz was subtherapeutic (less than 1.0 microg/ml) in 6 (8%) of 72 patients. In this South Indian population of HIV-infected patients, CYP2B6 G516T polymorphism but not RMP coadministration significantly influenced the pharmacokinetics of efavirenz; patients with the TT genotype had very high blood levels of efavirenz. While a small proportion of patients had subtherapeutic efavirenz levels, the clinical implications are uncertain, as all had good immunological responses to CART.

Asunto(s)

Fármacos Anti-VIH/farmacocinética , Hidrocarburo de Aril Hidroxilasas/genética , Benzoxazinas/farmacocinética , Infecciones por VIH/tratamiento farmacológico , Oxidorreductasas N-Desmetilantes/genética , Rifampin/uso terapéutico , Adulto , Alquinos , Antibióticos Antituberculosos/uso terapéutico , Ciclopropanos , Citocromo P-450 CYP2B6 , Quimioterapia Combinada , Femenino , Geografía , Infecciones por VIH/complicaciones , Infecciones por VIH/genética , VIH-1/genética , Humanos , India , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Rifampin/efectos adversos , Tuberculosis/complicaciones , Tuberculosis/tratamiento farmacológico

Asunto(s)

Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , VIH-1/genética , Polimorfismo Genético , Subfamilia B de Transportador de Casetes de Unión a ATP , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Adulto , Femenino , Genotipo , Infecciones por VIH/genética , Humanos , India , Masculino , Persona de Mediana Edad

RESUMEN

OBJECTIVES: To study the incidence and risk factors for failure of treatment with antiretroviral therapy among adults in the national treatment program in India, and to estimate the possible number of persons living with human immunodeficiency virus (HIV) who will need a second-line treatment regimen in the next 3 and 3.5 years. DESIGN AND SETTING: Data of a cohort of HIV-positive adult patients, who were enrolled in the government-sponsored antiretroviral therapy program, were obtained from the electronic medical record system of the largest HIV care center in India and subjected to analysis. MAIN OUTCOMES: Treatment failure defined by the World Health Organization criteria, assessed immunologically on the basis of CD4 T cell count, with a minimum period of 12 months of follow-up and with a minimum of two CD4 T cell follow-up measures. RESULTS: The cumulative incidence of treatment failure in the 1370 adult patients included in the study was 3.9% (95% confidence interval [CI] 2.9 to 4.9). Men had a 3.5 (1.6 to 7.4) times significantly greater risk of treatment failure. Patients who had negative changes in absolute lymphocyte count, hemoglobin concentration and body weight had 3.1 (1.6 to 6.2), 3.2 (1.6 to 6.2), and 3.5 (1.9 to 6.4) times significantly greater risk of treatment failure. In India, after 2007, by 2, 3, and 3.5 years, respectively, an estimated 16 000, 35 000, and 51 000 patients receiving antiretroviral therapy are likely to require second-line treatment. CONCLUSION: Monitoring of hemoglobin concentration, absolute lymphocyte count, and body weight during follow-up emerged as inexpensive predictors of treatment failure in a resource-poor setting. A significant number of patients will need second-line therapy as a result of failure of their first-line antiretroviral therapy regimen in 3 and 3.5 years in India, and therefore the development of an appropriate policy for second-line drugs is urgently needed.

Asunto(s)

Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Adolescente , Adulto , Terapia Antirretroviral Altamente Activa/métodos , Peso Corporal , Recuento de Linfocito CD4 , Métodos Epidemiológicos , Femenino , Programas de Gobierno , Infecciones por VIH/sangre , Infecciones por VIH/inmunología , Hemoglobinas/análisis , Humanos , India , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Cooperación del Paciente , Pronóstico , Factores Sexuales , Insuficiencia del Tratamiento

RESUMEN

Antiretroviral drug measurements as part of therapeutic drug monitoring are performed in several human immunodeficiency virus (HIV) clinics in developed as well as developing countries. Heparin is routinely used as an anticoagulant for plasma drug estimations. EDTA plasma for drug estimations, if found suitable, would have several practical advantages. In this study, plasma nevirapine (NVP) and efavirenz (EFV) levels were compared in paired blood collected in heparin and EDTA Vacutainer tubes (Greiner Bio-one, Austria). The study involved HIV-infected individuals who were receiving antiretroviral treatment at the Government Hospital of Thoracic Medicine, Tambaram, Chennai, India. Their treatment consisted of administration of NVP or EFV, along with lamivudine and stavudine/zidovudine. Blood was collected at the same time in heparin and EDTA Vacutainer tubes. Plasma concentrations of NVP and EFV were estimated, according to validated methods, by high-performance liquid chromatography (HPLC). The mean NVP concentrations in heparin and EDTA plasma were 8.79 and 8.59 microg/mL, respectively. This difference was not statistically significant (P = 0.203). In the case of EFV, the corresponding values were 3.03 and 2.78 microg/mL, respectively; the difference was significant (P < 0.05). However, the percent variation in EFV between both types of plasma was <10%. Blood collected in heparin or EDTA Vacutainer tubes could be used for plasma NVP determination.

Asunto(s)

Fármacos Anti-VIH/farmacocinética , Benzoxazinas/farmacocinética , Infecciones por VIH/tratamiento farmacológico , Nevirapina/farmacocinética , Adulto , Alquinos , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/uso terapéutico , Anticoagulantes , Benzoxazinas/administración & dosificación , Benzoxazinas/uso terapéutico , Ciclopropanos , Monitoreo de Drogas , Ácido Edético , Femenino , Infecciones por VIH/sangre , Heparina , Humanos , Masculino , Persona de Mediana Edad , Nevirapina/administración & dosificación , Nevirapina/uso terapéutico , Manejo de Especímenes

RESUMEN

India has approximately 5.2 million persons infected with HIV. Although antiretroviral therapy (ART) is being widely introduced in public clinics, many HIV-infected persons still seek care via the private sector. A cross-sectional survey was conducted in 2004 at six public and private sites to characterize the knowledge, attitudes, and practices (KAP) of ART among patients with HIV receiving care in India. Of 1667 persons surveyed, 609 (36%) had heard of ART and 19% of these persons reported that ART could cure HIV. Twenty-four percent reported that they were currently taking ART, with 18% of these patients not actually on ART according to their provider. Major barriers to taking ART were cost (33%), lack of knowledge of ART (41%), and deferral by physician (30%). More than half of all public and private patients had not heard of CD4 (57%) or viral load testing (80%), and even fewer had received these tests (32% and 11%, respectively). Private clinic attendees were almost 4 times more likely to be on ART (35% versus 9%, p < 0.0001), more likely to be male, have a higher education, be partnered, have a higher income, and have had a CD4 or viral load (p < 0.0001). Overall, low levels of ART knowledge and access were observed among HIV infected patients, with access to ART being particularly low among patients attending public clinics. In order to make widespread dissemination of ART effective in India, further educational and programmatic efforts are likely needed to optimize access, treatment awareness, and compliance among patients with HIV.

Asunto(s)

Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Conocimientos, Actitudes y Práctica en Salud , Cooperación del Paciente/estadística & datos numéricos , Adulto , Envejecimiento , Recuento de Linfocito CD4 , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/psicología , Humanos , India/epidemiología , India/etnología , Modelos Logísticos , Masculino , Oportunidad Relativa , Cooperación del Paciente/etnología , Cooperación del Paciente/psicología

RESUMEN

A total of 149 clinical isolates of Candida species isolated from immunocompromised patients were examined to ascertain their esterase activity by the Tween 80 opacity test, which is a biochemical test used mainly to differentiate between Candida albicans and Candida dubliniensis. Our results showed that C. albicans (92.3%), Candida tropicalis (92.3%), Candida parapsilosis (25%), C. dubliniensis (16.6%), Candida inconspicua (100%), and Candida lipolytica (100%) produced opacity halos through the 10-day post-inoculation period. The remaining Candida species did not produce a positive test response. These findings indicate that Tween 80 opacity test cannot be used as the sole phenotypic trait in the differentiation of C. albicans and C. dubliniensis.

Asunto(s)

Candida/enzimología , Candidiasis/microbiología , Esterasas/análisis , Proteínas Fúngicas/análisis , Candida/clasificación , Candida/aislamiento & purificación , Precipitación Química , Medios de Cultivo/metabolismo , Esterasas/metabolismo , Proteínas Fúngicas/metabolismo , Humanos , Hidrólisis , Huésped Inmunocomprometido , Luz , Fenotipo , Polisorbatos/metabolismo , Dispersión de Radiación , Especificidad de la Especie