HIV-infected TB Patients Research Articles

Prevalence and Associated Factors of Human Immune Deficiency Virus and Tuberculosis Co-Infection in Patients Attending Kolla Diba Health Center, Dembia District, Northwest Ethiopia.

BackgroundTB-HIV co-infection is the most common problem of African countries, especially, Sub-Saharan countries including Ethiopia. So this study aimed to assess TB-HIV co-infection with its associated factors in patients with Tuberculosis in Northwest Ethiopia. Although the prevalence of TB-HIV was low, the need for strengthening the health extension program especially in urban dwellers also needed to include TB-HIV testing.ObjectiveThis study aimed to assess TB-HIV co-infection with its associated factors in patients with Tuberculosis in Northwest Ethiopia.MethodologyInstitutional based cross-sectional study has been done and a total of 638 subjects participated in the study. The data of the study subjects were collected from the tuberculosis logbook using two trained data collectors who were work in the TB DOTS program and by using a well-prepared checklist and SPSS was used for analyzing data.Results9.7% (62/638) of TB patients were found to be co-infected with HIV. Among these 32 (11.4%) were females and 30 (8.4%) were males. More infected individuals were found in urban residents 44 (20%) than rural residents and age groups 30–40 years 31 (22.5%) are more infected than the other age group. TBforms, age, and residence were associated with HIV/TB co-infection significantly.Conclusions and RecommendationsAlthough the prevalence of TB-HIV was low, the need for strengthening the health extension program especially in urban dwellers is needed to include TB-HIV testing. Further surveys involving HIV infected TB patients to strengthen and scale-up for TB and HIV is needed.

Factors Associated with Tuberclosis-HIV Co-Infection in Diagnosis in the Nzanza Health Zone

Aim: To determine the factors associated with the increase in the proportion of HIV-infected TB patients of Kiamvu and Baobab Tuberculosis Screening and Treatment Health Center (TSTHC) in the Nzanza HZ, Matadi, between January 2012 and December 2017. Methods: This was a control case study of 187 HIV-positive TB patients and 187 HIV-negative TB patients followed at the Nzanza HZ Tuberculosis Screening and Treatment Health Center (TSTHC) from January 1, 2012 to December 31, 2017. We used Pearson’s Khi square test and homogeneity as well as logistic regression. This identified the factors associated with TB/HIV co-infection. Results: HIV-positive TB patients had a high daily household income [OR: 2.90; p: 0.000]) than HIV-negative people. The majority of HIV-positive TB patients had unprotected sex with a casual partner prior to diagnosis [OR: 1.82; p: 0.000]) than HIV-negative. After adjustment, alcohol intake [OR: 12.2; p: 0.004]) and extra pulmonary forms of tuberculosis [OR: 31.5; 0.002] were associated with increased TB/HIV co-infection. Conclusion: Alcohol intake and extra-pulmonary forms of tuberculosis were factors associated with increased TB/HIV co-infection. Awareness of TB patients may help reduce the risk of HIV infection.

Prevalence of diabetes mellitus among tuberculosis patients in Sub-Saharan Africa: a systematic review and meta-analysis of observational studies

BackgroundTuberculosis and diabetes mellitus are significant global public health challenges. In Sub-Saharan Africa, study findings regarding prevalence of diabetes mellitus amongst tuberculosis patients have been inconsistent and highly variable. Therefore, this systematic review and meta-analysis estimates the overall prevalence of diabetes mellitus among tuberculosis patients in Sub-Saharan Africa.MethodsFour international databases (PubMed, Google Scholar, Science Direct and Cochrane Library) were systematically searched. We included all observational studies reporting the prevalence of DM among TB patients in Sub-Saharan Africa. All necessary data for this review were extracted using a standardized data extraction format by two authors (CT and AA1). STATA Version 14 statistical software was employed to conduct meta-analysis. The Cochrane Q test statistics and I2 test were used to assess the heterogeneity of the studies. Finally, a random effects meta-analysis model was computed to estimate the pooled prevalence of diabetes mellitus in TB patients. Besides, subgroup analysis was done based on different factors.ResultsIn the meta-analysis, sixteen studies fulfilled the inclusion criteria and were included. The findings of these 16 studies revealed that the pooled prevalence of diabetes mellitus among tuberculosis patients in Sub-Saharan Africa was 9.0% (95% CI: 6.0, 12.0%). The highest prevalence of diabetes mellitus among tuberculosis patients was found in Nigeria (15%), followed by Tanzania (11%), and then Ethiopia (10%). Besides, the prevalence of diabetes mellitus among HIV infected TB patients was (8.9%) which is slightly higher than HIV uninfected (7.7%) TB patients.ConclusionDiabetes mellitus among tuberculosis patients in Sub-Saharan Africa was significantly high. Moreover, this study found that there was a high prevalence of DM among HIV infected than uninfected TB patients. It is strongly recommended to screen for DM among TB patients and special emphasis should be given for early screening of DM among TB/HIV co-infected patients.

Application of Poisson Mixed Combined Models for Identifying Correlations of CD4 Count Progression in HIV Infected TB Patients During ART Treatment Period

CD4 count is used to measures the number CD4 cells in the blood mostly during ART treatment to know the risk progression of HIV in the HIV infected patients. This continuously measured CD4 count during the treatment period results longitudinal data having correlation and over dispersion effects. While modeling such data to identify associated factors of change in CD4 count to monitor the progression of HIV most of the study did not considered these two main effects. The main aim of this study was also to consider these two main effect to identify the risk factors CD4 count progression based on 239 HIV infected TB patients who were 18 years old and above taking ART treatment from $1^{st}$ September 2009 to $1^{st}$ July 2014 at Jimma University Specialize Hospital. The result of study showed Poisson normal Gamma combine model which handles correlation and over dispersion effects of CD4 count simultaneously was an appropriate fit of the data among different Poisson mixed combined models considered for the study based on Akaki information criteria (AIC)comparisons. The estimated model depicts linear time and it's interaction effect with functional status category group of the patients have positive effect whereas quadratic time has the negative effect on the progression of CD4 count. The model also showed baseline bedridden and ambulatory functional status group patients has lower average CD4 count measurements in comparison with working functional status group patients counterparts. Therefore, while modeling CD4 count correlation and over dispersion should be taken in to consideration since the CD4 count value was correlated due to repeated measurement and it's variance larger than mean leading to over dispersion. Being at bedridden, ambulatory functional status at baseline in comparison with working functional status group and having quadratic time effects were also the associated risk factors that lowers the CD4 count measurements of the patients during the ART treatment period at the study area.

Whole genome sequencing reveals mycobacterial microevolution among concurrent isolates from sputum and blood in HIV infected TB patients.

BackgroundIn the context of advanced immunosuppression, M. tuberculosis is known to cause detectable mycobacteremia. However, little is known about the intra-patient mycobacterial microevolution and the direction of seeding between the sputum and blood compartments.MethodsFrom a diagnostic study of HIV-infected TB patients, 51 pairs of concurrent blood and sputum M. tuberculosis isolates from the same patient were available. In a previous analysis, we identified a subset with genotypic concordance, based on spoligotyping and 24 locus MIRU-VNTR. These paired isolates with identical genotypes were analyzed by whole genome sequencing and phylogenetic analysis.ResultsOf the 25 concordant pairs (49 % of the 51 paired isolates), 15 (60 %) remained viable for extraction of high quality DNA for whole genome sequencing. Two patient pairs were excluded due to poor quality sequence reads. The median CD4 cell count was 32 (IQR; 16–101)/mm3 and ten (77 %) patients were on ART. No drug resistance mutations were identified in any of the sequences analyzed. Three (23.1 %) of 13 patients had SNPs separating paired isolates from blood and sputum compartments, indicating evidence of microevolution.Using a phylogenetic approach to identify the ancestral compartment, in two (15 %) patients the blood isolate was ancestral to the sputum isolate, in one (8 %) it was the opposite, and ten (77 %) of the pairs were identical.ConclusionsAmong HIV-infected patients with poor cellular immunity, infection with multiple strains of M. tuberculosis was found in half of the patients. In those patients with identical strains, whole genome sequencing indicated that M. tuberculosis intra-patient microevolution does occur in a few patients, yet did not reveal a consistent direction of spread between sputum and blood. This suggests that these compartments are highly connected and potentially seed each other repeatedly.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1737-2) contains supplementary material, which is available to authorized users.

Predictors for MTB Culture-Positivity among HIV-Infected Smear-Negative Presumptive Tuberculosis Patients in Uganda: Application of New Tuberculosis Diagnostic Technology.

BackgroundThe existing World Health Organization diagnostic algorithms for smear-negative TB perform poorly in HIV-infected individuals. New TB diagnostics such as urine TB lipoarabinomannan (LAM) could improve the accuracy and reduce delays in TB diagnosis in HIV-infected smear-negative presumptive TB. We sought to determine predictors for MTB culture-positivity among these patients.MethodsThis study was nested into a prospective evaluation of HIV-infected outpatients and inpatients clinically suspected to have TB who were screened by smear-microscopy on two spot sputum samples. Data on socio-demographics, clinical symptoms, antiretroviral therapy, CXR, CD4 count, mycobacterial sputum and blood cultures and TB-LAM were collected. Logistic regression and conditional inference tree analysis were used to determine the most predictive indicators for MTB culture-positivity.ResultsOf the 418 smear-negative participants [female, 64%; median age (IQR) 32 (28-39) years, median CD4 106 (IQR 22 - 298) cells/mm3], 96/418 (23%) were sputum and/ or blood culture-positive for Mycobacterium tuberculosis (MTB) complex. Abnormal CXR (aOR 3.68, 95% CI 1.76- 7.71, p=0.001) and positive urine TB-LAM (aOR 6.21, 95% CI 3.14-12.27, p< 0.001) were significantly associated with MTB culture-positivity. Previous TB treatment (aOR 0.41, 95% CI 0.17-0.99, p=0.049) reduced the likelihood of a positive MTB culture. A conditional inference tree analysis showed that positive urine TB-LAM and abnormal CXR were the most predictive indicators of MTB culture-positivity. A combination of urine TB-LAM test and CXR had sensitivity and specificity of 50% and 86.1% respectively overall, and 70.8% and 84.1% respectively among those with CD4<100 cells/mm3.ConclusionsA positive urine TB-LAM test and an abnormal CXR significantly predict MTB culture-positivity among smear-negative HIV-infected presumptive TB patients while previous TB treatment reduces the likelihood of a positive MTB culture. Validation studies to assess the performance of diagnostic algorithms that include urine TB-LAM in the diagnosis of smear-negative TB in HIV-infected individuals are warranted.

RMP exposure is lower in HIV-infected TB patients receiving intermittent than daily anti-tuberculosis treatment

RMP exposure is lower in HIV-infected TB patients receiving intermittent than daily anti-tuberculosis treatment

Programmatic treatment outcomes in HIV-infected and uninfected drug-resistant TB patients in Khayelitsha, South Africa.

South Africa has high burdens of HIV, TB and drug-resistant TB (DR-TB, rifampicin-resistance). Treatment outcome data for HIV-infected versus uninfected patients is limited. We assessed the impact of HIV and other factors on DR-TB treatment success, time to culture conversion, loss-from-treatment and overall mortality after second-line treatment initiation. A retrospective cohort analysis was conducted for patients initiated on DR-TB treatment from 2008 to 2012, within a community-based, decentralised programme in Khayelitsha, South Africa. Among 853 confirmed DR-TB patients initiating second-line treatment, 605 (70.9%) were HIV infected. HIV status did not impact on time to sputum culture conversion nor did it impact treatment success; 48.1% (259/539) and 45.9% (100/218), respectively (p=0.59). In a multivariate model, HIV was not associated with treatment success. Death during treatment was higher among HIV-infected patients, but overall mortality was not significantly higher. HIV-infected patients with CD4 <=100 cells/ml were significantly more likely to die after starting treatment. Response to DR-TB treatment did not differ with HIV infection in a programmatic setting with access to antiretroviral treatment (ART). Earlier ART initiation at a primary care level could reduce mortality among HIV-infected patients presenting with low CD4 counts.

HIV infection and tuberculosis comorbidity: what is the cause of death?

The aim . The purpose of this study was to analyze causes of deaths of hospitalised HIV infected patients with tuberculosis. Methods . Medical reports of patients with tuberculosis who died in a specialized hospital of Samara city in 2013 were analyzed using the total sampling method. Results . Ninety per cent of deaths in hospitalised HIV infected TB patients were caused by end stage AIDS with the high proportion (82%) of miliary tuberculosis, involvement of multiple organs (53%) and drug dependence (88%). Conclusion . Improving interaction of TB specialists and experts on HIV infec tion is needed to improve statistic analysis of morbidity of and mortality from tuberculosis and to reduce mortality from these comorbid diseases.

The power of data: using routinely collected data to improve public health programmes and patient outcomes in low‐ and middle‐income countries

‘We are data rich, but information poor!’ So said one of the senior Ministry of Health officials in Fiji when a team from the International Union Against Tuberculosis and Lung Disease and the University of Fiji was discussing the start of an operational research capacity building initiative in that country two years ago. This statement probably sums up the situation for many Ministries of Health and NonGovernmental Organizations (NGOs) in lowand middleincome countries (LMIC), where large amounts of data are regularly collected and collated from health facilities, filed away or shelved and never used, analysed or interpreted to drive improved performance of health services, the scale up of interventions or better outcomes for patients. This paradigm needs to change. Furthermore, such data could be used in the context of operational research to ask more farreaching questions about quality, coverage, safety and effectiveness of programmes or health systems. National tuberculosis control programmes (NTPs) throughout the world serve as a model for data collection. One of the essential components of the WHO Stop TB Strategy is a standardised monitoring, evaluation and reporting system to account for all TB cases diagnosed along with their treatment outcomes through cohort monitoring (WHO 2006). Within well-functioning NTPs, TB officers review patient data every three months in terms of who and how many are accessing treatment, whether treatment outcomes are satisfactory, and whether adverse outcomes such as death or loss to follow-up are being kept to a minimum. These data are used to assess programme performance, and they also serve as the foundation for district and national drug forecasting and procurement. The routine data can also form the basis of operational research, which we define as research into strategies, interventions, tools or knowledge that can enhance the quality, coverage, effectiveness or performance of the health system or disease programme in which the research is being conducted (Zachariah et al. 2009). Between 1996 and 2005, the Malawi NTP formally incorporated operational research into its routine activities, and a large number of research projects were undertaken to improve policy and practice and reduce morbidity and mortality of patients (WHO 1999). One particular example concerned high case-fatality rates in HIV-infected TB patients before the advent of antiretroviral therapy (ART). The country undertook a series of district-based operational research studies to determine whether it was feasible to offer a package of HIV testing and cotrimoxazole preventive therapy (CPT) to TB patients registered under routine programme conditions (Harries et al. 2011). Using routinely collected data, and paying particular attention during this time to ensuring that mortality data were reliable and complete, the studies showed a significant reduction in death rates of between 20–25%. This evidence persuaded the Malawi Ministry of Health to support the scale up of HIV testing and CPT countrywide for TB patients, and activities started soon after completion of the research in 2003. Between 2002 and 2008, routinely collected data showed a significant increase in HIV testing amongst TB patients with the majority of HIVpositive patients being started on CPT. Treatment outcomes in new smear-positive pulmonary TB patients

Initiation of antiretroviral therapy in HIV‐infected tuberculosis patients in rural Kenya: an observational study

To provide information on the effect of timing of antiretroviral therapy (ART) initiation on outcomes of TB infection in real-life, non-clinical trial, rural settings in sub-Saharan Africa. We conducted an observational cohort study of all HIV-infected TB patients presenting to a rural hospital in Kenya between 2005 and 2009. We analysed the association between timing of initiation of ART and mortality, using a Cox regression survival analysis, adjusted for measured confounders. A total of 404 antiretroviral-naïve HIV/TB coinfected patients were included in the study. Initiation of ART during the first 8weeks of TB treatment (early group) was not associated with changes in mortality at 1year compared with initiation of ART after 8weeks (late group) [Hazard Ratio (HR)=0.74 (Confidence Interval (CI), 0.33-1.64, P=0.46]. In patients with baseline CD4 counts ≤50cells/μl, there was a significant reduction in mortality in the early group compared with the late group (HR=0.20; 95% CI, 0.042-0.99; P=0.049). In patients with a CD4 count >50cells/μl, there was no significant difference between early and late groups (HR 1.79; 95% CI, 0.64-5.03; P=0.27). We found that in HIV/TB coinfected patients in rural Kenya, early ART initiation (within 8weeks) was associated with reduced mortality in those with CD4 counts ≤50cells/μl. In patients with CD4 counts >50cells/μl, there was no association seen between timing of ART and mortality.

Comparison of Treatment Outcomes of New Smear-Positive Pulmonary Tuberculosis Patients by HIV and Antiretroviral Status in a TB/HIV Clinic, Malawi

BackgroundSmear-positive pulmonary TB is the most infectious form of TB. Previous studies on the effect of HIV and antiretroviral therapy on TB treatment outcomes among these highly infectious patients demonstrated conflicting results, reducing understanding of important issues.MethodsAll adult smear-positive pulmonary TB patients diagnosed between 2008 and 2010 in Malawi’s largest public, integrated TB/HIV clinic were included in the study to assess treatment outcomes by HIV and antiretroviral therapy status using logistic regression.ResultsOf 2,361 new smear-positive pulmonary TB patients, 86% had successful treatment outcome (were cured or completed treatment), 5% died, 6% were lost to follow-up, 1% failed treatment, and 2% transferred-out. Overall HIV prevalence was 56%. After adjusting for gender, age and TB registration year, treatment success was higher among HIV-negative than HIV-positive patients (adjusted odds ratio 1.49; 95% CI: 1.14–1.94). Of 1,275 HIV-infected pulmonary TB patients, 492 (38%) received antiretroviral therapy during the study. Pulmonary TB patients on antiretroviral therapy were more likely to have successful treatment outcomes than those not on ART (adjusted odds ratio : 1.83; 95% CI: 1.29–2.60).ConclusionHIV co-infection was associated with poor TB treatment outcomes. Despite high HIV prevalence and the integrated TB/HIV setting, only a minority of patients started antiretroviral therapy. Intensified patient education and provider training on the benefits of antiretroviral therapy could increase antiretroviral therapy uptake and improve TB treatment success among these most infectious patients.

Linkage to Care and Treatment for TB and HIV among People Newly Diagnosed with TB or HIV-Associated TB at a Large, Inner City South African Hospital

ObjectiveTo assess the outcomes of linkage to TB and HIV care and identify risk factors for poor referral outcomes.DesignCohort study of TB patients diagnosed at an urban hospital.MethodsLinkage to care was determined by review of clinic files, national death register, and telephone contact, and classified as linked to care, delayed linkage to care (>7 days for TB treatment, >30 days for HIV care), or failed linkage to care. We performed log-binomial regression to identify patient and referral characteristics associated with poor referral outcomes.ResultsAmong 593 TB patients, 23% failed linkage to TB treatment and 30.3% of the 77.0% who linked to care arrived late. Among 486 (86.9%) HIV-infected TB patients, 38.3% failed linkage to HIV care, and 32% of the 61.7% who linked to care presented late. One in six HIV-infected patients failed linkage to both TB and HIV care. Only 20.2% of HIV-infected patients were referred to a single clinic for integrated care. A referral letter was present in 90.3%, but only 23.7% included HIV status and 18.8% CD4 cell count. Lack of education (RR 1.85) and low CD4 count (CD4≤50 vs. >250cells/mm3; RR 1.66) were associated with failed linkage to TB care. Risk factors for failed linkage to HIV care were antiretroviral-naïve status (RR 1.29), and absence of referral letter with HIV or CD4 cell count (RR1.23).ConclusionsLinkage to TB/HIV care should be strengthened by communication of HIV and CD4 results, ART initiation during hospitalization and TB/HIV integration at primary care.

Diagnostic Accuracy of the GenoType MTBDR sl Assay for Rapid Diagnosis of Extensively Drug-Resistant Tuberculosis in HIV-Coinfected Patients

The Russian Federation is a high-tuberculosis (TB)-burden country with high rates of Mycobacterium tuberculosis multidrug resistance (MDR) and extensive drug resistance (XDR), especially in HIV-coinfected patients. Rapid and reliable diagnosis for detection of resistance to second-line drugs is vital for adequate patient management. We evaluated the performance of the GenoType MTBDRsl (Hain Lifescience GmbH, Nehren, Germany) assay on smear-positive sputum specimens obtained from 90 HIV-infected MDR TB patients from Russia. Test interpretability was over 98%. Specificity was over 86% for all drugs, while sensitivity varied, being the highest (71.4%) for capreomycin and lowest (9.4%) for kanamycin, probably due to the presence of mutations in the eis gene. The sensitivity of detection of XDR TB was 13.6%, increasing to 42.9% if kanamycin (not commonly used in Western Europe) was excluded. The assay is a highly specific screening tool for XDR detection in direct specimens from HIV-coinfected TB patients but cannot be used to rule out XDR TB.

Factors Associated with Survival Among Adults with HIV-Associated TB in Guangxi, China: A Retrospective Cohort Study

Aim: Although China has the second highest burden of TB in the world and faces a burgeoning HIV epidemic, the epidemiology and 12-month clinical outcomes of HIV-infected TB patients have not previously been reported. Methods: We reviewed records of all HIV-infected adults diagnosed with culture-confirmed TB from four HIV clinics in Guangxi, China from August 2006 to December 2008. Factors associated with patients’ survival within 12 months after TB diagnosis were evaluated in Cox proportional hazards models. Results: Among the 201 patients included, 47 (23%) died within 12 months. Median CD4 count at TB diagnosis was 37 cells/mm3 (interquartile range: 16–102). Receiving HAART (adjusted hazard ratio [AHR]: 4.2; 95% CI: 1.6–10.8), receiving TB treatment (AHR: 9.0; 95% CI: 1.5–53.5) and baseline BMI ≥ 18.5 (AHR: 8.4; 95% CI: 1.9–35.8) were independently associated with survival. Among 171 (85%) patients who received TB treatment, receiving HAART (HR: 5.1; 95% CI: 2.4–10.7) was the only factor significantly associated with survival. Conclusion: HIV-infected Chinese patients diagnosed with TB in Guangxi are at high risk of death within 12 months, a risk that is strongly mitigated by antiretroviral therapy. Improving survival from HIV-associated TB in China will require the integration of TB and HIV programs to improve access to treatment for both diseases.

Assessment at antiretroviral clinics during TB treatment reduces loss to follow-up among HIV-infected patients.

SettingA South African township clinic where loss to follow-up during TB treatment may prevent HIV-infected TB patients from receiving life-saving ART.ObjectiveTo determine factors associated with loss to follow-up during TB treatment.DesignRegression analyses of a cohort of ART-eligible TB patients who commenced TB treatment and were followed for 24 weeks.ResultsOf 111 ART-eligible TB patients, 15 (14%) died in the ensuing 24 weeks. Of the remaining 96 TB patients, 11 (11%) were lost to follow-up. All TB patients lost to follow-up did not initiate ART. Of 85 TB patients in follow-up, 62 (73%) initiated ART 56 days after TB diagnosis (median, IQR 33–77 days) and 31 days after initial assessment at an ART clinic (median, IQR: 18–55 days). The median duration from TB diagnosis to initial assessment at an ART clinic was 19 days (IQR: 7–48 days). At 24 weeks, 6 of 85 (7%) TB patients who presented to an ART clinic for assessment were lost to follow-up, compared to 5 of 11 (45%) TB patients who did not present to an ART clinic for assessment. Logistic regression analysis (adjusted odds ratio = 0.1, 95% confidence interval [95% CI]: 0.03–0.66) and our Cox proportional hazards model (hazard ratio = 0.2, 95% CI: 0.04–0.68) confirmed that assessment at an ART clinic during TB treatment reduced loss to follow-up.ConclusionAssessment at antiretroviral clinics for HIV care by trained health-care providers reduces loss to follow-up among HIV-infected patients with TB.

Advances in the Diagnosis, Treatment and Control of HIV Associated Tuberculosis.

There has been an increase in the number of published tuberculosis/HIV (TB/HIV) research findings in recent times. The potential impact of these findings on routine care has informed this review which aims at discussing current concepts and practices underpinning TB/HIV care and control. Any HIV infected person with a cough of any duration is currently considered a TB suspect. Preliminary results also show that the diagnostic yield of same day sputum samples (front loading) is comparable to two-day samples. Laboratory diagnosis is shifting from Ziehl-Neelsen (ZN) smear microscopy and solid culture to fluorescent microscopy, molecular tests and liquid culture. Concomitant TB/HIV therapy improves survival and WHO has recommended ART for all TB/HIV patients. Unless CD4 cell counts are less than 50 cells/µl, ART can be deferred until end of intensive phase. Evidence of survival benefit at high CD4 cell counts is still lacking. New TB drugs and treatment shortening studies are underway but so far no new TB drugs has been added to the current arsenal and treatment duration still remains six months or more. WHO has recommended the 31s (intensified TB case finding, isoniazid prophylaxis and infection control) for TB/HIV control in addition to effective therapy, Antiretroviral therapy and TB vaccines. There has been immense progress in TB/HIV research, however optimal management of HIV-Infected TB patients, will require further research and appropriate translation of emerging evidence to policy and practice.

Will Adoption of the 2010 WHO ART Guidelines for HIV-Infected TB Patients Increase the Demand for ART Services in India?

BackgroundIn 2010, WHO expanded previously-recommended indications for anti-retroviral treatment to include all HIV-infected TB patients irrespective of CD4 count. India, however, still limits ART to those TB patients with CD4 counts <350/mm3 or with extrapulmonary TB manifestations. We sought to evaluate the additional number of patients that would be initiated on ART if India adopted the current 2010 WHO ART guidelines for HIV-infected TB patients.MethodsWe evaluated all TB patients recorded in treatment registers of the Revised National TB Control Programme in June 2010 in the high-HIV prevalence state of Karnataka, and cross-matched HIV-infected TB patients with ART programme records.ResultsOf 6182 TB patients registered, HIV status was ascertained for 5761(93%) and 710(12%) were HIV-infected. 146(21%) HIV-infected TB patients were on ART prior to TB diagnosis. Of the remaining 564, 497(88%) were assessed for ART eligibility; of these, 436(88%) were eligible for ART according to 2006 WHO ART guidelines. Altogether, 487(69%) HIV-infected TB patients received ART during TB treatment. About 80% started ART within 8 weeks of TB treatment and 95% received an efavirenz based regimen.ConclusionIn Karnataka, India, about nine out of ten HIV-infected TB patients were eligible for ART according to 2006 WHO ART guidelines. The efficiency of HIV case finding, ART evaluation, and ART initiation was relatively high, with 78% of eligible HIV-infected patients actually initiated on ART, and 80% within 8 weeks of diagnosis. ART could be extended to all HIV-infected TB patients irrespective of CD4 count with relatively little additional burden on the national ART programme.

Operational research in Malawi: making a difference with cotrimoxazole preventive therapy in patients with tuberculosis and HIV

BackgroundIn Malawi, high case fatality rates in patients with tuberculosis, who were also co-infected with HIV, and high early death rates in people living with HIV during the initiation of antiretroviral treatment (ART) adversely impacted on treatment outcomes for the national tuberculosis and ART programmes respectively. This article i) discusses the operational research that was conducted in the country on cotrimoxazole preventive therapy, ii) outlines the steps that were taken to translate these findings into national policy and practice, iii) shows how the implementation of cotrimoxazole preventive therapy for both TB patients and HIV-infected patients starting ART was associated with reduced death rates, and iv) highlights lessons that can be learnt for other settings and interventions.DiscussionDistrict and facility-based operational research was undertaken between 1999 and 2005 to assess the effectiveness of cotrimoxazole preventive therapy in reducing death rates in TB patients and subsequently in patients starting ART under routine programme conditions. Studies demonstrated significant reductions in case fatality in HIV-infected TB patients receiving cotrimoxazole and in HIV-infected patients about to start ART. Following the completion of research, the findings were rapidly disseminated nationally at stakeholder meetings convened by the Ministry of Health and internationally through conferences and peer-reviewed scientific publications. The Ministry of Health made policy changes based on the available evidence, following which there was countrywide distribution of the updated policy and guidelines. Policy was rapidly moved to practice with the development of monitoring tools, drug procurement and training packages. National programme performance improved which showed a significant decrease in case fatality rates in TB patients as well as a reduction in early death in people with HIV starting ART.SummaryKey lessons for moving this research endeavour through to policy and practice were the importance of placing operational research within the programme, defining relevant questions, obtaining "buy-in" from national programme staff at the beginning of projects and having key actors or "policy entrepreneurs" to push forward the policy-making process. Ultimately, any change in policy and practice has to benefit patients, and the ultimate judge of success is whether treatment outcomes improve or not.

Treatment outcome and mortality at one and half year follow-up of HIV infected TB patients under TB control programme in a district of South India.

BackgroundThere is paucity of data from India on the impact of HIV related immunosuppression in response to TB treatment and mortality among HIV infected TB patients. We assessed the TB treatment outcome and mortality in a cohort of HIV infected TB patients treated with intermittent short course chemotherapy under TB control programme in a high HIV prevalent district of south India.Methodology/ FindingsAmong 3798 TB patients registered for treatment in Mysore district from July 2007 to June 2008, 281 HIV infected patients formed the study group. The socio-demographic and treatment related data of these patients was obtained from TB and HIV programme records and patient interviews 19 months after TB treatment initiation by field investigators. Treatment success rate of 281 patients was 75% while in smear positive pulmonary tuberculosis cases it was 62%, attributable to defaults (16%) and deaths (19%). Only 2 patients had treatment failure. Overall, 83 (30%) patients were reported dead; 26 while on treatment and 57 after TB treatment. Association of treatment related factors with treatment outcome and survival status was studied through logistic regression analysis. Factors significantly associated with ‘unfavourable outcome’ were disease classification as Pulmonary [aOR-1.96, CI (1.02–3.77)], type of patient as retreatment [aOR-4.78, CI (2.12–10.76)], and non initiation of ART [aOR-4.90, CI (1.85–12.96)]. Factors associated with ‘Death’ were non initiation of ART [aOR-2.80, CI (1.15–6.81)] and CPT [aOR-3.46, CI (1.47–8.14)].ConclusionDespite the treatment success of 75% the high mortality (30%) in the study group is a matter of concern and needs immediate intervention. Non initiation of ART has emerged as a high risk factor for unfavourable treatment outcome and mortality. These findings underscore the importance of expanding and improving delivery of ART services as a priority and reconsideration of the programme guidelines for ART initiation in HIV infected TB patients.