Gerardo Alvarez-Uria

Lung disease caused by nontuberculous mycobacteria.

Purpose of review Although the incidence of tuberculosis has reduced in developed countries, there is a growing interest in nontuberculous mycobacteria (NTM) as a cause of lung disease. However, NTM are a heterogeneous group and most of the data come from only three species: Mycobacterium avium complex, Mycobacterium kansasii and Mycobacterium abscessus. Still, information about these three species is confusing because it is based mainly on retrospective studies and series of clinical cases performed in developed countries. In recent years, new information has appeared about other species and the pathogenesis of NTM. Recent findings Epidemiological studies show that NTM infection is a worldwide phenomenon with an increasing presence in developing countries perhaps because of the implementation of tap water. Women with characteristic phenotype are at higher risk of acquiring NTM infection along with patients with defects on cystic fibrosis transmembrane conductance regulators. New studies on Mycobacterium fortuitum, Mycobacterium xenopi, Mycobacterium szulgai and Mycobacterium simiae indicate that the American Thoracic Society criteria for diagnosing NTM disease may not be useful for all species of NTM. Summary New multicentric and prospective studies are needed to clarify the pathogenesis and treatment of NTM. These organisms form a numerous and heterogeneous group and each species should be studied separately.

Rapid Diagnosis of Pulmonary and Extrapulmonary Tuberculosis in HIV-Infected Patients. Comparison of LED Fluorescent Microscopy and the GeneXpert MTB/RIF Assay in a District Hospital in India.

HIV-related tuberculosis is difficult to diagnose and is associated with high morbidity and mortality. Recently, the World Health Organization has endorsed the GeneXpert MTB/RIF (Xpert) assay for the diagnosis of pulmonary tuberculosis in HIV-infected patients from developing countries, but information about the use of Xpert for the diagnosis of extrapulmonary tuberculosis is scarce. In this study, we compared the performance of light-emitting diode (LED) auramine fluorescent microscopy and the Xpert assay for the diagnosis of tuberculosis in HIV infected patients in a district hospital of India. Although at higher cost, Xpert outperformed LED fluorescent microscopy in all type of specimens, especially in cerebrospinal fluid where the number of positive results was increased 11 times. Pleural fluid, ascitic fluid, pus, and stool specimens also yielded positive results with the Xpert assay. When collecting two additional early-morning sputum samples, the increase of the number of positive results with the Xpert assay was lower than previously reported for HIV infected patients. Rifampicin resistance was observed in 2.2% of the cases. The results of this study show that the Xpert assay can dramatically improve the rapid diagnosis of tuberculous meningitis and other types of extrapulmonary tuberculosis of HIV infected patients.

Entry, Retention, and Virological Suppression in an HIV Cohort Study in India: Description of the Cascade of Care and Implications for Reducing HIV-Related Mortality in Low- and Middle-Income Countries

HIV treatment, care, and support programmes in low- and middle-income countries have traditionally focused more on patients remaining in care after the initiation of antiretroviral therapy (ART) than on earlier stages of care. This study describes the cumulative retention from HIV diagnosis to the achievement of virological suppression after ART initiation in an HIV cohort study in India. Of all patients diagnosed with HIV, 70% entered into care within three months. 65% of patients ineligible for ART at the first assessment were retained in pre-ART care. 67% of those eligible for ART initiated treatment within three months. 30% of patients who initiated ART died or were lost to followup, and 82% achieved virological suppression in the last viral load determination. Most attrition occurred the in pre-ART stages of care, and it was estimated that only 31% of patients diagnosed with HIV engaged in care and achieved virological suppression after ART initiation. The total mortality attributable to pre-ART attrition was considerably higher than the mortality for not achieving virological suppression. This study indicates that early entry into pre-ART care along with timely initiation of ART is more likely to reduce HIV-related mortality compared to achieving virological suppression.

Factors associated with treatment failure of patients with psychiatric diseases and injecting drug users in the treatment of genotype 2 or 3 hepatitis C chronic infection

Background: Genotype 2/3 hepatitis C virus (HCV) has a good response to treatment with peginterferon and ribavirin. Patients with psychiatric disorders and injecting drug users (IDUs) are considered ‘difficult to treat’ and are often excluded from treatment despite the lack of evidence supporting this decision.

Factors associated with attrition, mortality, and loss to follow up after antiretroviral therapy initiation: data from an HIV cohort study in India

Background Studies from sub-Saharan Africa have shown high incidence of attrition due to mortality or loss to follow-up (LTFU) after initiating antiretroviral therapy (ART). India is the third largest country in the world in terms of HIV infected people, but predictors of attrition after ART initiation are not well known. Design We describe factors associated with attrition, mortality, and LTFU in 3,159 HIV infected patients who initiated ART between 1 January 2007 and 4 November 2011 in an HIV cohort study in India. The study included 6,852 person-years with a mean follow-up of 2.17 years. Results After 5 years of follow-up, the estimated cumulative incidence of attrition was 37.7%. There was no significant difference between attrition due to mortality and attrition due to LTFU. Having CD4 counts <100 cells/µl and being homeless [adjusted hazard ratio (aHR) 3.1, 95% confidence interval (CI) 2.6–3.8] were associated with a higher risk of attrition, and female gender (aHR 0.64, 95% CI 0.6–0.8) was associated with a reduced risk of attrition. Living near a town (aHR 0.82, 95% CI 0.7–0.999) was associated with a reduced risk of mortality. Being single (aHR 1.6, 95% CI 1.2–2.3), illiteracy (aHR 1.3, 95% CI 1.1–1.6), and age <25 years (aHR 1.3, 95% CI 1–1.8) were associated with an increased risk of LTFU. Although the cumulative incidence of attrition in patients diagnosed with tuberculosis after ART initiation was 47.4%, patients who started anti-tuberculous treatment before ART had similar attrition to patients without tuberculosis (36 vs. 35.2%, P=0.19) after four years of follow-up. Conclusions In this cohort study, the attrition was similar to the one found in sub-Saharan Africa. Earlier initiation of ART, improving the diagnosis of tuberculosis before initiating ART, and giving more support to those patients at higher risk of attrition could potentially reduce the mortality and LTFU after ART initiation.Background Studies from sub-Saharan Africa have shown high incidence of attrition due to mortality or loss to follow-up (LTFU) after initiating antiretroviral therapy (ART). India is the third largest country in the world in terms of HIV infected people, but predictors of attrition after ART initiation are not well known. Design We describe factors associated with attrition, mortality, and LTFU in 3,159 HIV infected patients who initiated ART between 1 January 2007 and 4 November 2011 in an HIV cohort study in India. The study included 6,852 person-years with a mean follow-up of 2.17 years. Results After 5 years of follow-up, the estimated cumulative incidence of attrition was 37.7%. There was no significant difference between attrition due to mortality and attrition due to LTFU. Having CD4 counts <100 cells/µl and being homeless [adjusted hazard ratio (aHR) 3.1, 95% confidence interval (CI) 2.6-3.8] were associated with a higher risk of attrition, and female gender (aHR 0.64, 95% CI 0.6-0.8) was associated with a reduced risk of attrition. Living near a town (aHR 0.82, 95% CI 0.7-0.999) was associated with a reduced risk of mortality. Being single (aHR 1.6, 95% CI 1.2-2.3), illiteracy (aHR 1.3, 95% CI 1.1-1.6), and age <25 years (aHR 1.3, 95% CI 1-1.8) were associated with an increased risk of LTFU. Although the cumulative incidence of attrition in patients diagnosed with tuberculosis after ART initiation was 47.4%, patients who started anti-tuberculous treatment before ART had similar attrition to patients without tuberculosis (36 vs. 35.2%, P=0.19) after four years of follow-up. Conclusions In this cohort study, the attrition was similar to the one found in sub-Saharan Africa. Earlier initiation of ART, improving the diagnosis of tuberculosis before initiating ART, and giving more support to those patients at higher risk of attrition could potentially reduce the mortality and LTFU after ART initiation.

Gender differences, routes of transmission, socio-demographic characteristics and prevalence of HIV related infections of adults and children in an HIV cohort from a rural district of India

Despite 67% of HIV infected people in India are rural residents, the epidemiology of HIV in rural areas is not well known. This is an observational cohort study of 11,040 HIV infected people living in a rural district of India. The prevalence of hepatitis B, hepatitis C and syphilis of HIV infected patients were compared to the seroprevalence in 16,641 blood donors from the same area. The age of diagnosis in adults was below 35 years in 70% of cases and 56% were illiterate. One third of women were widows and only 3.6% of adults had a permanent job. Women were diagnosed at earlier age, had lower level of education, had poorer employment conditions and depended more on their relatives than men. In a survey performed to a subgroup of patients, 81% of women referred to have acquired HIV from their spouse, whereas 51% of men acquired HIV from commercial sex. Patients with HIV had significantly higher prevalence of hepatitis B, hepatitis C and syphilis than blood donors. Seroprevalence of HIV-2, hepatitis C and toxoplasmosis were low compared to other sites. Six percent were children (<15 years) and almost half of them had lost one or both of their parents. The study shows the poor socio-economical situation and the high level of illiteracy of people living with HIV in rural India, especially women. Future health programmes of HIV in India should take into account the particularities of the HIV epidemic in rural areas.

Effect of Formula Feeding and Breastfeeding on Child Growth, Infant Mortality, and HIV Transmission in Children Born to HIV-Infected Pregnant Women Who Received Triple Antiretroviral Therapy in a Resource-Limited Setting: Data from an HIV Cohort Study in India

We describe a programme for the prevention of mother-to-child transmission (PMTCT) of HIV that provided universal antiretroviral therapy (ART) to all pregnant women regardless of the CD4 lymphocyte count and formula feeding for children with high risk of HIV transmission through breastfeeding in a district of India. The overall rate of HIV transmission was 3.7%. Although breastfeeding added a 3.1% additional risk of HIV acquisition, formula-fed infants had significantly higher risk of death compared to breastfed infants. The cumulative 12-month mortality was 9.6% for formula-fed infants versus 0.68% for breastfed infants. Anthropometric markers (weight, length/height, weight for length/height, body mass index, head circumference, mid-upper arm circumference, triceps skinfold, and subscapular skinfold) showed that formula-fed infants experience severe malnutrition during the first two months of life. We did not observe any death after rapid weaning at 5-6 months in breastfed infants. The higher-free-of HIV survival in breastfed infants and the low rate of HIV transmission found in this study support the implementation of PMTCT programmes with universal ART to all HIV-infected pregnant women and breastfeeding in order to reduce HIV transmission without increasing infant mortality in developing countries.

Factors Associated with Late Presentation of HIV and Estimation of Antiretroviral Treatment Need according to CD4 Lymphocyte Count in a Resource-Limited Setting: Data from an HIV Cohort Study in India

We describe the CD4 lymphocyte count at HIV presentation in an HIV cohort from a rural district of India. The majority of patients were diagnosed for their HIV-related symptoms, although a sizeable proportion of women were diagnosed because of antenatal screening or for having an HIV-positive partner. Patients diagnosed of HIV for antenatal screening or having an HIV-positive sexual partner had higher CD4 lymphocyte count than patients having tuberculosis or HIV-related symptoms. The proportion of patients diagnosed with CD4 count <200 and <350 cells/mm3 were 46% and 68.7%, respectively, and these figures did not change during the five years of the study. Factors associated with late presentations were male sex, older age, not having a permanent house, and, in women, lower education and being a widow or separated. With the implementation of 2010 WHO guidelines, the number of newly diagnosed patients who will require HIV treatment will increase 13.8%. If the CD4 count threshold for initiating HIV treatment is increased from 350 to 500 cells/mm3, the number of patients in need of treatment would increase 15.7%. Therefore, new strategies for avoiding HIV late presentation are urgently needed in developing countries.

Prevalence and Severity of Anaemia Stratified by Age and Gender in Rural India

Anaemia is a major public health problem in India. Although nearly three quarters of the Indian population live in rural areas, the epidemiology of anaemia in rural settings is not well known. We performed a retrospective observational study using routine clinical data from patients attending the out-patient clinics of a rural hospital in India from June 2011 to August 2014. The study included 73,795 determinations of haemoglobin. 49.5% of patients were female. The median haemoglobin concentration was 11.3 g/dL (interquartile range (IQR), 9.8–12.4) in females and 12.5 g/dL (IQR, 10.6–14.2) in males. Anaemia was present in the majority of children <10 years, women after puberty, and older adults. Children <5 years had the highest prevalence of anaemia, especially children aged 1-2 years. The high proportion of microcytic anaemia and the fact that gender differences were only seen after the menarche period in women suggest that iron deficiency was the main cause of anaemia. However, the prevalence of normocytic anaemia increased with age. The results of this study can be used by public health programmes to design target interventions aimed at reducing the huge burden of anaemia in India. Further studies are needed to clarify the aetiology of anaemia among older adults.

Computational models can predict response to HIV therapy without a genotype and may reduce treatment failure in different resource-limited settings

OBJECTIVES Genotypic HIV drug-resistance testing is typically 60%-65% predictive of response to combination antiretroviral therapy (ART) and is valuable for guiding treatment changes. Genotyping is unavailable in many resource-limited settings (RLSs). We aimed to develop models that can predict response to ART without a genotype and evaluated their potential as a treatment support tool in RLSs. METHODS Random forest models were trained to predict the probability of response to ART (≤400 copies HIV RNA/mL) using the following data from 14 891 treatment change episodes (TCEs) after virological failure, from well-resourced countries: viral load and CD4 count prior to treatment change, treatment history, drugs in the new regimen, time to follow-up and follow-up viral load. Models were assessed by cross-validation during development, with an independent set of 800 cases from well-resourced countries, plus 231 cases from Southern Africa, 206 from India and 375 from Romania. The area under the receiver operating characteristic curve (AUC) was the main outcome measure. RESULTS The models achieved an AUC of 0.74-0.81 during cross-validation and 0.76-0.77 with the 800 test TCEs. They achieved AUCs of 0.58-0.65 (Southern Africa), 0.63 (India) and 0.70 (Romania). Models were more accurate for data from the well-resourced countries than for cases from Southern Africa and India (P < 0.001), but not Romania. The models identified alternative, available drug regimens predicted to result in virological response for 94% of virological failures in Southern Africa, 99% of those in India and 93% of those in Romania. CONCLUSIONS We developed computational models that predict virological response to ART without a genotype with comparable accuracy to genotyping with rule-based interpretation. These models have the potential to help optimize antiretroviral therapy for patients in RLSs where genotyping is not generally available.