Enhancing TB Case Detection: Experience in Offering Upfront Xpert MTB/RIF Testing to Pediatric Presumptive TB and DR TB Cases for Early Rapid Diagnosis of Drug Sensitive and Drug Resistant TB

Background

Diagnosis of pulmonary tuberculosis (PTB) in children is challenging due to difficulties in obtaining good quality sputum specimens as well as the paucibacillary nature of disease. Globally a large proportion of pediatric tuberculosis (TB) cases are diagnosed based only on clinical findings. Xpert MTB/RIF, a highly sensitive and specific rapid tool, offers a promising solution in addressing these challenges. This study presents the results from pediatric groups taking part in a large demonstration study wherein Xpert MTB/RIF testing replaced smear microscopy for all presumptive PTB cases in public health facilities across India.

Methods

The study covered a population of 8.8 million across 18 programmatic sub-district level tuberculosis units (TU), with one Xpert MTB/RIF platform established at each study TU. Pediatric presumptive PTB cases (both TB and Drug Resistant TB (DR-TB)) accessing any public health facilities in study area were prospectively enrolled and tested on Xpert MTB/RIF following a standardized diagnostic algorithm.

Results

4,600 pediatric presumptive pulmonary TB cases were enrolled. 590 (12.8%, CI 11.8–13.8) pediatric PTB were diagnosed. Overall 10.4% (CI 9.5–11.2) of presumptive PTB cases had positive results by Xpert MTB/RIF, compared with 4.8% (CI 4.2–5.4) who had smear-positive results. Upfront Xpert MTB/RIF testing of presumptive PTB and presumptive DR-TB cases resulted in diagnosis of 79 and 12 rifampicin resistance cases, respectively. Positive predictive value (PPV) for rifampicin resistance detection was high (98%, CI 90.1–99.9), with no statistically significant variation with respect to past history of treatment.

Conclusion

Upfront access to Xpert MTB/RIF testing in pediatric presumptive PTB cases was associated with a two-fold increase in bacteriologically-confirmed PTB, and increased detection of rifampicin-resistant TB cases under routine operational conditions across India. These results suggest that routine Xpert MTB/RIF testing is a promising solution to present-day challenges in the diagnosis of PTB in pediatric patients.     

Use of Xpert MTB/RIF in Decentralized Public Health Settings and Its Effect on Pulmonary TB and DR-TB Case Finding in India

BackgroundXpert MTB/RIF, the first automated molecular test for tuberculosis, is transforming the diagnostic landscape in high-burden settings. This study assessed the impact of up-front Xpert MTB/RIF testing on detection of pulmonary tuberculosis (PTB) and rifampicin-resistant PTB (DR-TB) cases in India.MethodsThis demonstration study was implemented in 18 sub-district level TB programme units (TUs) in India in diverse geographic and demographic settings covering a population of 8.8 million. A baseline phase in 14 TUs captured programmatic baseline data, and an intervention phase in 18 TUs had Xpert MTB/RIF offered to all presumptive TB patients. We estimated changes in detection of TB and DR-TB, the former using binomial regression models to adjust for clustering and covariates.ResultsIn the 14 study TUs, which participated in both phases, 10,675 and 70,556 presumptive TB patients were enrolled in the baseline and intervention phase, respectively, and 1,532 (14.4%) and 14,299 (20.3%) bacteriologically confirmed PTB cases were detected. The implementation of Xpert MTB/RIF was associated with increases in both notification rates of bacteriologically confirmed TB cases (adjusted incidence rate ratio [aIRR] 1.39; CI 1.18-1.64), and proportion of bacteriological confirmed TB cases among presumptive TB cases (adjusted risk ratio (aRR) 1.33; CI 1.6-1.52). Compared with the baseline strategy of selective drug-susceptibility testing only for PTB cases at high risk of drug-resistant TB, Xpert MTB/RIF implementation increased rifampicin resistant TB case detection by over fivefold. Among, 2765 rifampicin resistance cases detected, 1055 were retested with conventional drug susceptibility testing (DST). Positive predictive value (PPV) of rifampicin resistance detected by Xpert MTB/RIF was 94.7% (CI 91.3-98.1), in comparison to conventional DST.ConclusionIntroduction of Xpert MTB/RIF as initial diagnostic test for TB in public health facilities significantly increased case-notification rates of all bacteriologically confirmed TB by 39% and rifampicin-resistant TB case notification by fivefold.     

Evaluation of Cepheid's Xpert MTB/RIF Test on Pleural Fluid in the Diagnosis of Pleural Tuberculosis in a High Prevalence HIV/TB Setting

Background

Diagnosis of pleural tuberculosis (TB) using routinely available diagnostic methods is challenging due to the paucibacillary nature of the disease. Histopathology and pleural tissue TB culture involves an invasive procedure which requires expertise and appropriate equipment, both often unavailable in many health units. Xpert MTB/Rif test has been widely evaluated in sputum specimens but data on its performance in pleural TB is scarce. We evaluated the accuracy of Cepheid''s Xpert MTB/Rif test on pleural fluid in the diagnosis of pleural TB in Uganda.

Methods

Consenting adult patients with exudative pleural effusions underwent pleural biopsy and the tissue obtained subjected to Lowenstein-Jensen and mycobacterial growth indicator tube MTB cultures and histopathology. Pleural fluid for Xpert MTB/Rif testing was also collected. Data on socio-demographic characteristics, clinical symptoms, HIV status and CD4 count were also collected. Sensitivity, specificity, positive and negative predictive values of Xpert MTB/Rif test on pleural fluid in pleural TB diagnosis were calculated using pleural tissue MTB culture and/or histopathology as the reference standard.

Results

Of the 116 participants [female 50%, mean age 34 (SD ±13], 87/116 (75%) had pleural TB confirmed on pleural tissue culture and/or histopathology. The Xpert MTB/Rif test identified 25 (28.7%) of the 87 confirmed pleural TB cases. The sensitivity and specificity of Xpert MTB/Rif test were 28.7% and 96.6% respectively while the positive and negative predictive values were 96.1% and 31.1% respectively.

Conclusion

Xpert MTB/Rif test on pleural fluid does not accurately diagnose pleural TB and therefore cannot be used as an initial evaluation test in patients with suspected pleural TB. New, rapid and accurate tests for the diagnosis of pleural TB are still warranted.     

Optimal Triage Test Characteristics to Improve the Cost-Effectiveness of the Xpert MTB/RIF Assay for TB Diagnosis: A Decision Analysis

Background

High costs are a limitation to scaling up the Xpert MTB/RIF assay (Xpert) for the diagnosis of tuberculosis in resource-constrained settings. A triaging strategy in which a sensitive but not necessarily highly specific rapid test is used to select patients for Xpert may result in a more affordable diagnostic algorithm. To inform the selection and development of particular diagnostics as a triage test we explored combinations of sensitivity, specificity and cost at which a hypothetical triage test will improve affordability of the Xpert assay.

Methods

In a decision analytical model parameterized for Uganda, India and South Africa, we compared a diagnostic algorithm in which a cohort of patients with presumptive TB received Xpert to a triage algorithm whereby only those with a positive triage test were tested by Xpert.

Findings

A triage test with sensitivity equal to Xpert, 75% specificity, and costs of US$5 per patient tested reduced total diagnostic costs by 42% in the Uganda setting, and by 34% and 39% respectively in the India and South Africa settings. When exploring triage algorithms with lower sensitivity, the use of an example triage test with 95% sensitivity relative to Xpert, 75% specificity and test costs $5 resulted in similar cost reduction, and was cost-effective by the WHO willingness-to-pay threshold compared to Xpert for all in Uganda, but not in India and South Africa. The gain in affordability of the examined triage algorithms increased with decreasing prevalence of tuberculosis among the cohort.

Conclusions

A triage test strategy could potentially improve the affordability of Xpert for TB diagnosis, particularly in low-income countries and with enhanced case-finding. Tests and markers with lower accuracy than desired of a diagnostic test may fall within the ranges of sensitivity, specificity and cost required for triage tests and be developed as such.     

Implementation Research to Inform the Use of Xpert MTB/RIF in Primary Health Care Facilities in High TB and HIV Settings in Resource Constrained Settings

BackgroundThe current cost of Xpert MTB RIF (Xpert) consumables is such that algorithms are needed to select which patients to prioritise for testing with Xpert.ObjectiveTo evaluate two algorithms for prioritisation of Xpert in primary health care settings in a high TB and HIV burden setting.MethodConsecutive, presumptive TB patients with a cough of any duration were offered either Xpert or Fluorescence microscopy (FM) test depending on their CXR score or HIV status. In one facility, sputa from patients with an abnormal CXR were tested with Xpert and those with a normal CXR were tested with FM (“CXR algorithm”). CXR was scored automatically using a Computer Aided Diagnosis (CAD) program. In the other facility, patients who were HIV positive were tested using Xpert and those who were HIV negative were tested with FM (“HIV algorithm”).ResultsOf 9482 individuals pre-screened with CXR, Xpert detected TB in 2090/6568 (31.8%) with an abnormal CXR, and FM was AFB positive in 8/2455 (0.3%) with a normal CXR. Of 4444 pre-screened with HIV, Xpert detected TB in 508/2265 (22.4%) HIV positive and FM was AFB positive in 212/1920 (11.0%) in HIV negative individuals. The notification rate of new bacteriologically confirmed TB increased; from 366 to 620/ 100,000/yr and from 145 to 261/100,000/yr at the CXR and HIV algorithm sites respectively. The median time to starting TB treatment at the CXR site compared to the HIV algorithm site was; 1(IQR 1-3 days) and 3 (2-5 days) (p<0.0001) respectively.ConclusionUse of Xpert in a resource-limited setting at primary care level in conjunction with pre-screening tests reduced the number of Xpert tests performed. The routine use of Xpert resulted in additional cases of confirmed TB patients starting treatment. However, there was no increase in absolute numbers of patients starting TB treatment. Same day diagnosis and treatment commencement was achieved for both bacteriologically confirmed and empirically diagnosed patients where Xpert was used in conjunction with CXR.     

Comparison of Xpert MTB/RIF with other nucleic acid technologies for diagnosing pulmonary tuberculosis in a high HIV prevalence setting: a prospective study

Background

The Xpert MTB/RIF (Cepheid) non-laboratory-based molecular assay has potential to improve the diagnosis of tuberculosis (TB), especially in HIV-infected populations, through increased sensitivity, reduced turnaround time (2 h), and immediate identification of rifampicin (RIF) resistance. In a prospective clinical validation study we compared the performance of Xpert MTB/RIF, MTBDRplus (Hain Lifescience), LightCycler Mycobacterium Detection (LCTB) (Roche), with acid fast bacilli (AFB) smear microscopy and liquid culture on a single sputum specimen.

Methods and Findings

Consecutive adults with suspected TB attending a primary health care clinic in Johannesburg, South Africa, were prospectively enrolled and evaluated for TB according to the guidelines of the National TB Control Programme, including assessment for smear-negative TB by chest X-ray, clinical evaluation, and HIV testing. A single sputum sample underwent routine decontamination, AFB smear microscopy, liquid culture, and phenotypic drug susceptibility testing. Residual sample was batched for molecular testing. For the 311 participants, the HIV prevalence was 70% (n = 215), with 120 (38.5%) culture-positive TB cases. Compared to liquid culture, the sensitivities of all the test methodologies, determined with a limited and potentially underpowered sample size (n = 177), were 59% (47%–71%) for smear microscopy, 76% (64%–85%) for MTBDRplus, 76% (64%–85%) for LCTB, and 86% (76%–93%) for Xpert MTB/RIF, with specificities all >97%. Among HIV+ individuals, the sensitivity of the Xpert MTB/RIF test was 84% (69%–93%), while the other molecular tests had sensitivities reduced by 6%. TB detection among smear-negative, culture-positive samples was 28% (5/18) for MTBDRplus, 22% (4/18) for LCTB, and 61% (11/18) for Xpert MTB/RIF. A few (n = 5) RIF-resistant cases were detected using the phenotypic drug susceptibility testing methodology. Xpert MTB/RIF detected four of these five cases (fifth case not tested) and two additional phenotypically sensitive cases.

Conclusions

The Xpert MTB/RIF test has superior performance for rapid diagnosis of Mycobacterium tuberculosis over existing AFB smear microscopy and other molecular methodologies in an HIV- and TB-endemic region. Its place in the clinical diagnostic algorithm in national health programs needs exploration. Please see later in the article for the Editors'' Summary     

Impact of Replacing Smear Microscopy with Xpert MTB/RIF for Diagnosing Tuberculosis in Brazil: A Stepped-Wedge Cluster-Randomized Trial

BackgroundAbundant evidence on Xpert MTB/RIF accuracy for diagnosing tuberculosis (TB) and rifampicin resistance has been produced, yet there are few data on the population benefit of its programmatic use. We assessed whether the implementation of Xpert MTB/RIF in routine conditions would (1) increase the notification rate of laboratory-confirmed pulmonary TB to the national notification system and (2) reduce the time to TB treatment initiation (primary endpoints).ConclusionsReplacing smear microscopy with Xpert MTB/RIF in Brazil increased confirmation of pulmonary TB. An additional benefit was the accurate detection of rifampicin resistance. However, no increase on overall notification rates was observed, possibly because of high rates of empirical TB treatment.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01363765","term_id":"NCT01363765"}}NCT01363765Please see later in the article for the Editors'' Summary     

Comparison of Xpert MTB/RIF Assay and GenoType MTBDRplus DNA Probes for Detection of Mutations Associated with Rifampicin Resistance in Mycobacterium tuberculosis

BackgroundGeneXpert MTB/RIF (Xpert) and Genotype MTBDRplus (DRplus) are two World Health Organization (WHO) endorsed probe based molecular drug susceptibility testing (DST) methods for rapid diagnosis of drug resistant tuberculosis. Both methods target the same 81 bp Rifampicin Resistance Determining Region (RRDR) of bacterial RNA polymerase β subunit (rpoB) for detection of Rifampicin (RIF) resistance associated mutations using DNA probes. So there is a correspondence of the probes of each other and expected similarity of probe binding.MethodsWe analyzed 92 sputum specimens by Xpert, DRplus and LJ proportion method (LJ-DST). We compared molecular DSTs with gold standard LJ-DST. We wanted to see the agreement level of two molecular methods for detection of RIF resistance associated mutations. The 81bp RRDR region of rpoB gene of discrepant cases between the two molecular methods was sequenced by Sanger sequencing.ResultsThe agreement of Xpert and DRplus with LJ-DST for detection of RIF susceptibility was found to be 93.5% and 92.4%, respectively. We also found 92.4% overall agreement of two molecular methods for the detection of RIF susceptibility. A total of 84 out of 92 samples (91.3%) had agreement on the molecular locus of RRDR mutation by DRplus and Xpert. Sanger sequencing of 81bp RRDR revealed that Xpert probes detected seven of eight discrepant cases correctly and DRplus was erroneous in all the eight cases.ConclusionAlthough the overall concordance with LJ-DST was similar for both Xpert and DRplus assay, Xpert demonstrated more accuracy in the detection of RIF susceptibility for discrepant isolates compared with DRplus. This observation would be helpful for the improvement of probe based detection of drug resistance associated mutations especially rpoB mutation in M. tuberculosis.     

Direct Detection by the Xpert MTB/RIF Assay and Characterization of Multi and Poly Drug-Resistant Tuberculosis in Guinea-Bissau,West Africa

BackgroundThis study aimed to evaluate the usefulness of the Xpert MTB/RIF assay for the rapid direct detection of M. tuberculosis complex (MTBC) strains and rifampicin resistance associated mutations in a resource-limited setting such as Guinea-Bissau and its implications in the management of tuberculosis (TB) and drug resistant tuberculosis, complementing the scarce information on resistance and genotypic diversity of MTBC strains in this West African country.ConclusionsThe Xpert MTB/RIF assay was reliable for the detection of rifampicin resistant MTBC strains directly from sputum samples of patients undergoing first-line treatment for two months, being more trustworthy than the simple presence of acid-fast bacilli in the smear. Its implementation is technically simple, does not require specialized laboratory infrastructures and is suitable for resource-limited settings when a regular source of electricity and maintenance is available as well as financial and operation sustainability is guaranteed by the health authorities. A high prevalence of MDR-TB among patients at risk of MDR-TB after two months of first-line treatment was found, in support of the WHO recommendations for its use in the management of this risk group.     

Rapid diagnosis of tuberculosis with the Xpert MTB/RIF assay in high burden countries: a cost-effectiveness analysis

Background

Xpert MTB/RIF (Xpert) is a promising new rapid diagnostic technology for tuberculosis (TB) that has characteristics that suggest large-scale roll-out. However, because the test is expensive, there are concerns among TB program managers and policy makers regarding its affordability for low- and middle-income settings.

Methods and Findings

We estimate the impact of the introduction of Xpert on the costs and cost-effectiveness of TB care using decision analytic modelling, comparing the introduction of Xpert to a base case of smear microscopy and clinical diagnosis in India, South Africa, and Uganda. The introduction of Xpert increases TB case finding in all three settings; from 72%–85% to 95%–99% of the cohort of individuals with suspected TB, compared to the base case. Diagnostic costs (including the costs of testing all individuals with suspected TB) also increase: from US$28–US$49 to US$133–US$146 and US$137–US$151 per TB case detected when Xpert is used “in addition to” and “as a replacement of” smear microscopy, respectively. The incremental cost effectiveness ratios (ICERs) for using Xpert “in addition to” smear microscopy, compared to the base case, range from US$41–$110 per disability adjusted life year (DALY) averted. Likewise the ICERS for using Xpert “as a replacement of” smear microscopy range from US$52–$138 per DALY averted. These ICERs are below the World Health Organization (WHO) willingness to pay threshold.

Conclusions

Our results suggest that Xpert is a cost-effective method of TB diagnosis, compared to a base case of smear microscopy and clinical diagnosis of smear-negative TB in low- and middle-income settings where, with its ability to substantially increase case finding, it has important potential for improving TB diagnosis and control. The extent of cost-effectiveness gain to TB programmes from deploying Xpert is primarily dependent on current TB diagnostic practices. Further work is required during scale-up to validate these findings. Please see later in the article for the Editors'' Summary     

Time to Treatment and Patient Outcomes among TB Suspects Screened by a Single Point-of-Care Xpert MTB/RIF at a Primary Care Clinic in Johannesburg,South Africa

Introduction

In December 2010, the World Health Organization recommended a single Xpert MTB/RIF assay as the initial diagnostic in people suspected of HIV-associated or drug resistant tuberculosis. Few data are available on the impact of this recommendation on patient outcomes. We describe the diagnostic follow-up, clinical characteristics and outcomes of a cohort of tuberculosis suspects screened using a single point-of-care Xpert.

Methods

Consecutive tuberculosis suspects at a primary care clinic in Johannesburg, South Africa were assessed for tuberculosis using point-of-care Xpert. Sputum smear microscopy and liquid culture were performed as reference standards. Xpert-negatives were evaluated clinically, and further assessed at the discretion of clinicians. Participants were followed for six months.

Results

From July-September 2011, 641 tuberculosis suspects were enrolled, of whom 69% were HIV-infected. Eight percent were positive by a single Xpert. Among 116 individuals diagnosed with TB, 66 (57%) were Xpert negative, of which 44 (67%) were empirical or radiological diagnoses and 22 (33%) were Xpert negative/culture-positive. The median time to tuberculosis treatment was 0 days (IQR: 0–0) for Xpert positives, 14 days (IQR: 5–35) for those diagnosed empirically, 14 days (IQR: 7–29) for radiological diagnoses, and 144 days (IQR: 28–180) for culture positives. Xpert negative tuberculosis cases were clinically similar to Xpert positives, including HIV status and CD4 count, and had similar treatment outcomes including mortality and time to antiretroviral treatment initiation.

Conclusions

In a high HIV-burden setting, a single Xpert identified less than half of those started on tuberculosis treatment, highlighting the complexity of TB diagnosis even in the Xpert era. Xpert at point-of-care resulted in same day treatment initiation in Xpert-positives, but had no impact on tuberculosis treatment outcomes or mortality.     

The Sensitivity and Specificity of Using a Computer Aided Diagnosis Program for Automatically Scoring Chest X-Rays of Presumptive TB Patients Compared with Xpert MTB/RIF in Lusaka Zambia

Objective

To determine the sensitivity and specificity of a Computer Aided Diagnosis (CAD) program for scoring chest x-rays (CXRs) of presumptive tuberculosis (TB) patients compared to Xpert MTB/RIF (Xpert).

Method

Consecutive presumptive TB patients with a cough of any duration were offered digital CXR, and opt out HIV testing. CXRs were electronically scored as normal (CAD score ≤60) or abnormal (CAD score>60) using a CAD program. All patients regardless of CAD score were requested to submit a spot sputum sample for testing with Xpert and a spot and morning sample for testing with LED Fluorescence Microscopy-(FM).

Results

Of 350 patients with evaluable data, 291 (83.1%) had an abnormal CXR score by CAD. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CXR compared to Xpert were 100% (95%CI 96.2–100), 23.2% (95%CI 18.2–28.9), 33.0% (95%CI 27.6–38.7) and 100% (95% 93.9–100), respectively. The area under the receiver operator curve (AUC) for CAD was 0.71 (95%CI 0.66–0.77). CXR abnormality correlated with smear grade (r = 0.30, p<0.0001) and with Xpert C_T(r = 0.37, p<0.0001).

Conclusions

To our knowledge this is the first time that a CAD program for TB has been successfully tested in a real world setting. The study shows that the CAD program had high sensitivity but low specificity and PPV. The use of CAD with digital CXR has the potential to increase the use and availability of chest radiography in screening for TB where trained human resources are scarce.     

Diagnostic Accuracy of Quantitative PCR (Xpert MTB/RIF) for Tuberculous Meningitis in a High Burden Setting: A Prospective Study

Background

Tuberculous meningitis (TBM) is difficult to diagnose promptly. The utility of the Xpert MTB/RIF test for the diagnosis of TBM remains unclear, and the effect of host- and sample-related factors on test performance is unknown. This study sought to evaluate the sensitivity and specificity of Xpert MTB/RIF for the diagnosis of TBM.

Methods and Findings

235 South-African patients with a meningeal-like illness were categorised as having definite (culture or Amplicor PCR positive), probable (anti-TBM treatment initiated but microbiological confirmation lacking), or non-TBM. Xpert MTB/RIF accuracy was evaluated using 1 ml of uncentrifuged and, when available, 3 ml of centrifuged cerebrospinal fluid (CSF). To evaluate the incremental value of MTB/RIF over a clinically based diagnosis, test accuracy was compared to a clinical score (CS) derived using basic clinical and laboratory information.Of 204 evaluable patients (of whom 87% were HIV-infected), 59 had definite TBM, 64 probable TBM, and 81 non-TBM. Overall sensitivity and specificity (95% CI) were 62% (48%–75%) and 95% (87%–99%), respectively. The sensitivity of Xpert MTB/RIF was significantly better than that of smear microscopy (62% versus 12%; p = 0.001) and significantly better than that of the CS (62% versus 30%; p = 0.001; C statistic 85% [79%–92%]). Xpert MTB/RIF sensitivity was higher when centrifuged versus uncentrifuged samples were used (82% [62%–94%] versus 47% [31%–61%]; p = 0.004). The combination of CS and Xpert MTB/RIF (Xpert MTB/RIF performed if CS<8) performed as well as Xpert MTB/RIF alone but with a ∼10% reduction in test usage. This overall pattern of results remained unchanged when the definite and probable TBM groups were combined. Xpert MTB/RIF was not useful in identifying TBM among HIV-uninfected individuals, although the sample was small. There was no evidence of PCR inhibition, and the limit of detection was ∼80 colony forming units per millilitre. Study limitations included a predominantly HIV-infected cohort and the limited number of culture-positive CSF samples.

Conclusions

Xpert MTB/RIF may be a good rule-in test for the diagnosis of TBM in HIV-infected individuals from a tuberculosis-endemic setting, particularly when a centrifuged CSF pellet is used. Further studies are required to confirm these findings in different settings. Please see later in the article for the Editors'' Summary     

Re-Validation of the Van Rie HIV/AIDS-Related Stigma Scale for Use with People Living with HIV in the United States

There is little consensus about which of the many validated human immunodeficiency virus (HIV) stigma scales should be regularly used, with few being re-validated in different contexts or evaluated for how they compare to other, existing HIV stigma scales. The purpose of this exploratory study was to re-validate the Van Rie HIV/AIDS-Related Stigma Scale, originally validated in Thailand and using a third-person wording structure, for use with people living with HIV in the United States. Adult HIV clinic patients completed a survey including the Berger and Van Rie scales, and measures of social support and depression. Eighty-five of 211 (40%) eligible participants provided data for both stigma scales. Exploratory factor analyses identified three factors to the Van Rie scale: Loss of Social Relationships (new subscale), Managing HIV Concealment (new subscale), and Perceived Community Stigma (original subscale). These subscales were moderately inter-related (r = 0.51 to 0.58) with acceptable to excellent reliability (Cronbach’s alpha = 0.69 to 0.90). The Van Rie subscales were also moderately inter-correlated with the Berger subscales (r = 0.44 to 0.76), had similar construct validity, and tended to have higher mean stigma scores when compared with Berger subscales that were conceptually most similar. The revised Van Rie HIV-related Stigma Scale demonstrates good validity and internal consistency, offering a valid measure of HIV stigma with a three-factor structure. The third-person wording may be particularly suitable for measuring stigmatizing attitudes during an individual’s transition from at-risk and undergoing HIV testing to newly diagnosed, a time when experiences of discrimination and processing issues of disclosure have not yet occurred. The stigma mechanisms for individuals making this transition have not been well explored. These scenarios, combined with the observed non-response to the Berger Enacted Stigma subscale items (a surprise finding), highlight gaps in our understanding of HIV stigma and how best to measure it.     

Distribution and Determinants of Cytomegalovirus Induced End Organ Disease/s among People Living with HIV/AIDS in a Poor Resource Setting: Observation from India

BackgroundIn India, despite well-established anti-retroviral treatment programs, Cytomegalovirus (CMV) infection-related end-organ diseases (EODs) still remain a major concern resulting in exacerbation of morbidity and mortality among HIV/AIDS patients. A prospective study was designed to understand the distribution and prognosis of CMV associated EODs and to determine a standardized cut-off value for serum CMV viral load associated with the development of EODs amongst HIV/AIDS subjects.MethodsIn a cohort of 400 late-diagnosed HAART naïve HIV/AIDS subjects attending anti-retroviral centers of Kolkata during 2008–2014, the median duration of follow-up was 560 days, and at least 3 visits subsequent to the baseline were mandatory for eligibility. HIV-1 and CMV viral load were estimated by performing Real-Time Polymerase Chain Reactions (PCR).ResultsAmong subjects, 40.5% (162/400) had CMV EODs which were more common at lower CD4 counts. Poor prognosis and higher death rate were associated with a low CD4 count and increased HIV-1 and CMV viral loads. Subjects having higher CD4 count responded better to therapy [for CD4 = 60–100: Risk Ratio:RR = 1.48 (95% Confidence Interval: 95%CI = 1.18–1.82) and for CD4 = 30–59: RR = 1.64 (95%CI = 1.18–2.27)]. The cut off value of the serum CMV viral load (expressed as log10DNA/ml serum) associated with the development of EODs and disseminated CMV EODs was determined as 5.4 (p<0.0001) and 6.4 (p<0.0001) respectively. These cut offs were found to have satisfactorily high sensitivity, specificity, positive and negative predictive values.ConclusionPrognosis of CMV EOD was poor as indicated by higher death rates among subjects with lower CD4 count, and specific cut-off values were found to have useful potential for identification and treatment of CMV infected HIV/AIDS patients in due time to avoid CMV EODs among HIV/AIDS subjects. Targeted intervention programs seemed to be required urgently to make these cut-offs operational in order to minimize the burden of CMV EOD in this vulnerable population.     

Substance Use and Psychosocial Status among People Living with HIV/AIDS Who Encountered HIV Stigma in China: Stratified Analyses by Socio-Economic Status

This study examined whether the impact of HIV stigma on psychosocial status and substance use among people living with HIV/AIDS (PLWHA) differed by their socio-economic status (SES) in a Chinese setting. A total of 2,987 PLWHA were recruited from 12 sites with the highest number of cumulative HIV incidence in Guangxi, China. Participants were asked to provide information regarding their psychosocial status (e.g., depression, anxiety), history of substance use (e.g., tobacco, alcohol and drug) and SES (e.g., education, monthly income, residence type, and job category). By employing stratified multivariate regression analyses, we assessed stratum-specific impacts of HIV stigma on PLWHA’s psychosocial status and behaviors of substance use based upon participants’ SES. The impact of HIV stigma differed significantly on psychosocial status across SES gradients. Psychosocial status among people with higher education was more sensitive to HIV stigma compared with PLWHA who were less educated. The odds of substance use behaviors were higher among people with better monthly income than their low-income peers. Our study is the first paper to document the paucity of SES stratified analyses between HIV stigma and psychosocial status and substance use among PLWHA in China. We call for tailored intervention programs to target PLWHA with different backgrounds and characteristics in order to help them to better manage their seropositivity.     

Caring for Caregivers of People Living with HIV in the Family: A Response to the HIV Pandemic from Two Urban Slum Communities in Pune,India

Introduction

In low resource settings, the vast majority of ‘Person/people Living with HIV’ (PLHIV/s) and inadequate healthcare delivery systems to meet their treatment and care needs, caregivers play a vital role. Home based caregivers are often unrecognized with limited AIDS policies and programs focusing on them. We explored the perceptions and norms regarding care being provided by family caregivers of PLHIVs in India.

Methodology

A community based qualitative study to understand the issues pertaining to home based care for PLHIV was conducted in urban settings of Pune city, in Maharashtra, India. Eight Focus Group Discussions (FGDs) among men, women and peer educators were carried out. A total of 44 in-depth Interviews (IDIs) with PLHIVs (20) and their caregivers (24), were conducted using separate guides respectively. Data was analyzed thematically.

Results

Home based care was perceived as economically viable option available for PLHIVs. ‘Care’ comprised of emotional, adherence, nursing and financial support to PLHIV. Home based care was preferred over hospital based care as it ensured confidentiality and patient care without hampering routine work at home. Women emerged as more vital primary caregivers compared to men. Home based care for men was almost unconditional while women had no such support. The natal family of women also abandoned. Their marital families seemed to provide support. Caregivers voiced the need for respite care and training.

Discussion

Gender related stigma and discrimination existed irrespective of women being the primary family caregivers. The support from marital families indicates a need to explore care and support issues at natal and marital homes of the women living with HIV respectively. Home based care training and respite care for the caregivers is recommended. Gender sensitive interventions addressing gender inequity and HIV related stigma should be modeled while designing interventions for PLHIVs and their family caregivers.