E. Jane Carter

Misclassification of First-Line Antiretroviral Treatment Failure Based on Immunological Monitoring of HIV Infection in Resource-Limited Settings

BACKGROUND The monitoring of patients with human immunodeficiency virus (HIV) infection who are treated with antiretroviral medications in resource-limited settings is typically performed by use of clinical and immunological criteria. The early identification of first-line antiretroviral treatment failure is critical to prevent morbidity, mortality, and drug resistance. Misclassification of failure may result in premature switching to second-line therapy. METHODS Adult patients in western Kenya had their viral loads (VLs) determined if they had adhered to first-line therapy for >6 months and were suspected of experiencing immunological failure (ie, their CD4 cell count decreased by 25% in 6 months). Misclassification of treatment failure was defined as a 25% decrease in CD4 cell count with a VL of <400 copies/mL. Logistic and tree regressions examined relationships between VL and 4 variables: CD4 T cell count (hereafter CD4 cell count), percentage of T cells expressing CD4 (hereafter CD4 cell percentage), percentage decrease in the CD4 T cell count (hereafter CD4 cell count percent decrease), and percentage decrease in the percentage of T cells expressing CD4 (hereafter CD4% percent decrease). RESULTS There were 149 patients who were treated for 23 months; they were identified as having a 25% decrease in CD4 cell count (from 375 to 216 cells/microL) and a CD4% percent decrease (from 19% to 15%); of these 149 patients, 86 (58%) were misclassified as having experienced treatment failure. Of 42 patients who had a 50% decrease in CD4 cell count, 18 (43%) were misclassified. In multivariate logistic regression, misclassification odds were associated with a higher CD4 cell count, a shorter duration of therapy, and a smaller CD4% percent decrease. By combining these variables, we may be able to improve our ability to predict treatment failure. CONCLUSIONS Immunological monitoring as a sole indicator of virological failure would lead to a premature switch to valuable second-line regimens for 58% of patients who experience a 25% decrease in CD4 cell count and for 43% patients who experience a 50% decrease in CD4 cell count, and therefore this type of monitoring should be reevaluated. Selective virological monitoring and the addition of indicators like trends CD4% percent decrease and duration of therapy may systematically improve the identification of treatment failure. VL testing is now mandatory for patients suspected of experiencing first-line treatment failure within the Academic Model Providing Access to Healthcare (AMPATH) in western Kenya, and should be considered in all resource-limited settings.

Results from early programmatic implementation of Xpert MTB/RIF testing in nine countries

BackgroundThe Xpert MTB/RIF assay has garnered significant interest as a sensitive and rapid diagnostic tool to improve detection of sensitive and drug resistant tuberculosis. However, most existing literature has described the performance of MTB/RIF testing only in study conditions; little information is available on its use in routine case finding. TB REACH is a multi-country initiative focusing on innovative ways to improve case notification.MethodsWe selected a convenience sample of nine TB REACH projects for inclusion to cover a range of implementers, regions and approaches. Standard quarterly reports and machine data from the first 12 months of MTB/RIF implementation in each project were utilized to analyze patient yields, rifampicin resistance, and failed tests. Data was collected from September 2011 to March 2013. A questionnaire was implemented and semi-structured interviews with project staff were conducted to gather information on user experiences and challenges.ResultsAll projects used MTB/RIF testing for people with suspected TB, as opposed to testing for drug resistance among already diagnosed patients. The projects placed 65 machines (196 modules) in a variety of facilities and employed numerous case-finding strategies and testing algorithms. The projects consumed 47,973 MTB/RIF tests. Of valid tests, 7,195 (16.8%) were positive for MTB. A total of 982 rifampicin resistant results were found (13.6% of positive tests). Of all tests conducted, 10.6% failed. The need for continuous power supply was noted by all projects and most used locally procured solutions. There was considerable heterogeneity in how results were reported and recorded, reflecting the lack of standardized guidance in some countries.ConclusionsThe findings of this study begin to fill the gaps among guidelines, research findings, and real-world implementation of MTB/RIF testing. Testing with Xpert MTB/RIF detected a large number of people with TB that routine services failed to detect. The study demonstrates the versatility and impact of the technology, but also outlines various surmountable barriers to implementation. The study is not representative of all early implementer experiences with MTB/RIF testing but rather provides an overview of the shared issues as well as the many different approaches to programmatic MTB/RIF implementation.

Hypertension and Obesity as Cardiovascular Risk Factors among HIV Seropositive Patients in Western Kenya

Background There is increased risk of cardiovascular disease among HIV seropositive individuals. The prevalence of HIV is highest in sub-Saharan Africa; however, HIV-related cardiovascular risk research is largely derived from developed country settings. Herein, we describe the prevalence of hypertension and obesity in a large HIV treatment program in Kenya. Methods We performed a retrospective analysis of the electronic medical records of a large HIV treatment program in Western Kenya between 2006 and 2009. We calculated the prevalence of hypertension and obesity among HIV+ adults as well as utilized multiple logistic regression analyses to examine the relationship between clinical characteristics, HIV-related characteristics, and hypertension. Results Our final sample size was 12,194. The median systolic/diastolic blood pressures were similar for both sexes (male: 110/70 mmHg, female: 110/70 mmHg). The prevalence of hypertension among men and women were 11.2% and 7.4%, respectively. Eleven percent of men and 22.6% of women were overweight/obese (body mass index ≥25 kg/m2). Ordinal logistic regression analyses showed that overweight/obesity was more strongly associated with hypertension among HIV+ men (OR 2.41, 95% CI 1.88–3.09) than a higher successive age category (OR 1.62, 95% CI 1.40–1.87 comparing 16–35, 36–45 and >45 years categories). Among women, higher age category and overweight/obesity were most strongly associated with hypertension (age category: OR 2.21, 95% CI 1.95–2.50, overweight/obesity: OR 1.80, 95% CI 1.50–2.16). Length of time on protease inhibitors was not found to be related to hypertension for men (OR 1.62, 95% CI 0.42–6.20) or women (OR 1.17, 95% CI 0.37–2.65) after adjustment for CD4 count, age and BMI. Conclusion In Western Kenya, there is a high prevalence of hypertension and overweight/obesity among HIV+ patients with differences observed between men and women. The care of HIV+ patients in sub-Saharan Africa should also include both identification and management of associated cardiovascular risk factors.

Mycobacterium tuberculosis lineage 4 comprises globally distributed and geographically restricted sublineages

Generalist and specialist species differ in the breadth of their ecological niches. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that, whereas the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists. Our data further support a European origin for the most common generalist sublineage. Hence, the global success of lineage 4 reflects distinct strategies adopted by different sublineages and the influence of human migration.

Impact of integrated family planning and HIV care services on contraceptive use and pregnancy outcomes: a retrospective cohort study.

ObjectiveTo determine the impact of routine care (RC) and integrated family planning (IFP) and HIV care service on family planning (FP) uptake and pregnancy outcomes. DesignRetrospective cohort study conducted between October 10, 2005, and February 28, 2009. SettingUnited States Agency for International Development—Academic Model Providing Access To Healthcare (USAID-AMPATH) in western Kenya. SubjectsRecords of adult HIV-infected women. InterventionIntegration of FP into one of the care teams. Primary Outcomes MeasuresIncidence of FP methods and pregnancy. ResultsFour thousand thirty-one women (1453 IFP; 2578 RC) were eligible. Among the IFP group, there was a 16.7% increase (P < 0.001) [95% confidence interval (CI): 13.2% to 20.2%] in incidence of condom use, 12.9% increase (P < 0.001) (95% CI: 9.4% to 16.4%) in incidence of FP use including condoms, 3.8% reduction (P < 0.001) (95% CI: 1.9% to 5.6%) in incidence of FP use excluding condoms, and 0.1% increase (P = 0.9) (95% CI: −1.9% to 2.1%) in incidence of pregnancies. The attributable risk of the incidence rate per 100 person-years of IFP and RC for new condom use was 16.4 (95% CI: 11.9 to 21.0), new FP use including condoms was 13.5 (95% CI: 8.7 to 18.3), new FP use excluding condoms was −3.0 (95% CI: −4.6 to −1.4) and new cases of pregnancies was 1.2 (95% CI: −0.6 to 3.0). ConclusionsIntegrating FP services into HIV care significantly increased the use of modern FP methods but no impact on pregnancy incidence. HIV programs need to consider integrating FP into their program structure.

The clinical burden of tuberculosis among human immunodeficiency virus-infected children in Western Kenya and the impact of combination antiretroviral treatment.

Context: The burden of tuberculosis (TB) disease in children, particularly in HIV-infected children, is poorly described because of a lack of effective diagnostic tests and the emphasis of public health programs on transmissible TB. Objectives: The objectives of this study were to describe the observed incidence of and risk factors for TB diagnosis among HIV-infected children enrolled in a large network of HIV clinics in western Kenya. Design: Retrospective observational study. Setting: The USAID-Academic Model Providing Access to Healthcare (AMPATH) Partnership is Kenya’s largest HIV/AIDS care system. Since 2001, the program has enrolled over 70,000 HIV-infected patients in 18 clinics throughout Western Kenya. Patients: This analysis included all HIV-infected children aged 0 to 13 years attending an AMPATH clinic. Main Outcome Measure: The primary outcome was a diagnosis of any TB, defined either by a recorded diagnosis or by the initiation of anti-TB treatment. Diagnosis of TB is based on a modified Kenneth Jones scoring system and is consistent with WHO case definitions. Results: There were 6535 HIV-infected children aged 0 to 13 years, eligible for analysis, 50.1% were female. Of these, 234 (3.6%) were diagnosed with TB at enrollment. There were subsequently 765 new TB diagnoses in 4368.0 child-years of follow-up for an incidence rate of 17.5 diagnoses (16.3–18.8) per 100 child-years. The majority of these occurred in the first 6 months after enrollment (IR: 106.8 per 100 CY, 98.4–115.8). In multivariable analysis, being severely immune-suppressed at enrollment (Adjusted Hazard Ratio [AHR]: 4.44, 95% CI: 3.62–5.44), having ever attended school AHR: 2.65, 95% CI: 2.15–3.25), being an orphan (AHR: 1.57, 95% CI: 1.28–1.92), being severely low weight-for-height at enrollment (AHR: 1.46, 95% CI: 1.32–1.62), and attending an urban clinic (AHR: 1.39, 95% CI: 1.16–1.67) were all independent risk factors for having an incident TB diagnosis. Children receiving combination antiretroviral treatment were dramatically less likely to be diagnosed with incident TB (AHR: 0.15, 95% CI: 0.12–0.20). Conclusions: These data suggest a high rate of TB diagnosis among HIV-infected children, with severe immune suppression, school attendance, orphan status, very low weight-for-height, and attending an urban clinic being key risk factors. The use of combination antiretroviral treatment reduced the probability of an HIV-infected child being diagnosed with incident TB by 85%.

Chronic noncommunicable cardiovascular and pulmonary disease in sub-Saharan Africa: An academic model for countering the epidemic

Noncommunicable diseases are rapidly overtaking infectious, perinatal, nutritional, and maternal diseases as the major causes of worldwide death and disability. It is estimated that, within the next 10 to 15 years, the increasing burden of chronic diseases and the aging of the population will expose the world to an unprecedented burden of chronic diseases. Preventing the potential ramifications of a worldwide epidemic of chronic noncommunicable diseases in a sustainable manner requires coordinated, collaborative efforts. Herein, we present our collaborations strategic plan to understand, treat, and prevent chronic cardiovascular and pulmonary disease (CVPD) in western Kenya, which builds on a 2-decade partnership between academic universities in North America and Kenya, the Academic Model Providing Access to Healthcare. We emphasize the importance of training Kenyan clinician-investigators who will ultimately lead efforts in CVPD care, education, and research. This penultimate aim will be achieved by our 5 main goals. Our goals include creating an administrative core capable of managing operations, develop clinical and clinical research training curricula, enhancing existing technology infrastructure, and implementing relevant research programs. Leveraging a strong international academic partnership with respective expertise in cardiovascular medicine, pulmonary medicine, and medical informatics, we have undertaken to understand and counter CVPD in Kenya by addressing patient care, teaching, and clinical research.

Impact of Immigration on the Molecular Epidemiology of Tuberculosis in Rhode Island

ABSTRACT While foreign-born persons constitute only 11% of the population in the state of Rhode Island, they account for more than 65% of incident tuberculosis (TB) annually. We investigated the molecular-epidemiological differences between foreign-born and U.S.-born TB patients to estimate the degree of recent transmission and identify predictors of clustering. A total of 288 isolates collected from culture-confirmed TB cases in Rhode Island between 1995 and 2004 were fingerprinted by spoligotyping and 12-locus mycobacterial interspersed repetitive units. Of the 288 fingerprinted isolates, 109 (37.8%) belonged to 36 genetic clusters. Our findings demonstrate that U.S.-born patients, Hispanics, Asian/Pacific islanders, and uninsured patients were significantly more likely to be clustered. Recent transmission among the foreign-born population was restricted and occurred mostly locally, within populations originating from the same region. Nevertheless, TB transmission between the foreign-born and U.S.-born population should not be neglected, since 80% of the mixed clusters of foreign- and U.S.-born persons arose from a foreign-born source case. We conclude that timely access to routine screening and treatment for latent TB infection for immigrants is vital for disease elimination in Rhode Island.

Women and Lung Disease. Sex Differences and Global Health Disparities

There is growing evidence that a number of pulmonary diseases affect women differently and with a greater degree of severity than men. The causes for such sex disparity is the focus of this Blue Conference Perspective review, which explores basic cellular and molecular mechanisms, life stages, and clinical outcomes based on environmental, sociocultural, occupational, and infectious scenarios, as well as medical health beliefs. Owing to the breadth of issues related to women and lung disease, we present examples of both basic and clinical concepts that may be the cause for pulmonary disease disparity in women. These examples include those diseases that predominantly affect women, as well as the rising incidence among women for diseases traditionally occurring in men, such as chronic obstructive pulmonary disease. Sociocultural implications of pulmonary disease attributable to biomass burning and infectious diseases among women in low- to middle-income countries are reviewed, as are disparities in respiratory health among sexual minority women in high-income countries. The implications of the use of complementary and alternative medicine by women to influence respiratory disease are examined, and future directions for research on women and respiratory health are provided.

Low correlation between household carbon monoxide and particulate matter concentrations from biomass-related pollution in three resource-poor settings.

Household air pollution from the burning of biomass fuels is recognized as the third greatest contributor to the global burden of disease. Incomplete combustion of biomass fuels releases a complex mixture of carbon monoxide (CO), particulate matter (PM) and other toxins into the household environment. Some investigators have used indoor CO concentrations as a reliable surrogate of indoor PM concentrations; however, the assumption that indoor CO concentration is a reasonable proxy of indoor PM concentration has been a subject of controversy. We sought to describe the relationship between indoor PM2.5 and CO concentrations in 128 households across three resource-poor settings in Peru, Nepal, and Kenya. We simultaneously collected minute-to-minute PM2.5 and CO concentrations within a meter of the open-fire stove for approximately 24h using the EasyLog-USB-CO data logger (Lascar Electronics, Erie, PA) and the personal DataRAM-1000AN (Thermo Fisher Scientific Inc., Waltham, MA), respectively. We also collected information regarding household construction characteristics, and cooking practices of the primary cook. Average 24h indoor PM2.5 and CO concentrations ranged between 615 and 1440 μg/m(3), and between 9.1 and 35.1 ppm, respectively. Minute-to-minute indoor PM2.5 concentrations were in a safe range (<25 μg/m(3)) between 17% and 65% of the time, and exceeded 1000 μg/m(3) between 8% and 21% of the time, whereas indoor CO concentrations were in a safe range (<7 ppm) between 46% and 79% of the time and exceeded 50 ppm between 4%, and 20% of the time. Overall correlations between indoor PM2.5 and CO concentrations were low to moderate (Spearman ρ between 0.59 and 0.83). There was also poor agreement and evidence of proportional bias between observed indoor PM2.5 concentrations vs. those estimated based on indoor CO concentrations, with greater discordance at lower concentrations. Our analysis does not support the notion that indoor CO concentration is a surrogate marker for indoor PM2.5 concentration across all settings. Both are important markers of household air pollution with different health and environmental implications and should therefore be independently measured.