Patients In South Africa Research Articles

Viral suppression following switch to second-line antiretroviral therapy: associations with nucleoside reverse transcriptase inhibitor resistance and subtherapeutic drug concentrations prior to switch.

Background. High rates of second-line antiretroviral treatment (ART) failure are reported. The association with resistance and nonadherence on switching to second-line ART requires clarification.Methods. Using prospectively collected data from patients in South Africa, we constructed a cohort of patients switched to second-line ART (1 January 2003 through 31 December 2008). Genotyping and drug concentrations (lamivudine, nevirapine, and efavirenz) were measured on stored samples preswitch. Their association with viral load (VL) <400 copies/mL by 15 months was assessed using modified Poisson regression.Results. One hundred twenty-two of 417 patients (49% male; median age, 36 years) had genotyping (n = 115) and/or drug concentrations (n = 80) measured. Median CD4 count and VL at switch were 177 cells/µL (interquartile range [IQR], 77–263) and 4.3 log10 copies/mL (IQR, 3.8–4.7), respectively. Fifty-five percent (n = 44/80) had subtherapeutic drug concentrations preswitch. More patients with therapeutic vs subtherapeutic ART had resistance (n = 73): no major mutations (3% vs 51%), nonnucleoside reverse transcriptase inhibitor (94% vs 44%), M184V/I (94% vs 26%), and ≥1 thymidine analogue mutations (47% vs 18%), all P = .01; and nucleoside reverse transcriptase inhibitor (NRTI) cross-resistance mutations (26% vs 13%, P = .23). Following switch, 68% (n = 83/122) achieved VL <400 copies/mL. Absence of NRTI mutations and subtherapeutic ART preswitch were associated with failure to achieve VL <400 copies/mL.Conclusions. Nonadherence, suggested by subtherapeutic ART with/without major resistance mutations, significantly contributed to failure when switching regimen. Unresolved nonadherence, not NRTI resistance, drives early second-line failure.

AB0281 Remission rates during golimumab treatment for rheumatoid arthritis are associated with differences in baseline disease states across geographic regions in the go-more study

BackgroundRegional differences in practice patterns and access to biologic treatment for rheumatoid arthritis (RA) may lead to regional differences in baseline disease characteristics, which could influence response to biologic treatments.ObjectivesTo...

Oncothermia in HIV-Positive and -Negative Locally Advanced Cervical Cancer Patients in South Africa

Aim. Investigate the clinical, economic, and cellular effects of the addition of oncothermia to standard treatment for HIV-positive and -negative locally advanced cervical cancer patients in public healthcare in South Africa. Objectives. Evaluate the effect that the addition of oncothermia has on local disease control, progression-free survival, overall survival at 2 years, treatment toxicity, quality of life, economic impact, and HIV status of participants. Radiobiology investigations will evaluate thermoradiosensitivity and the molecular markers for thermoradiosensitivity. Methodology. Phase III randomised clinical trial involving 236 HIV-negative and -positive stage IIb-III locally advanced cervical cancer patients. Treatment includes cisplatin, external beam radiation, and brachytherapy. The study group will receive oncothermia treatments. Participants will be monitored for two years after completion of treatment. Hypothesis. The addition of oncothermia to standard treatment protocols will result in improved clinical response without increasing treatment toxicity in HIV-positive patients or raising healthcare costs.

Stargardt Disease: towards developing a model to predict phenotype

Stargardt disease is an ABCA4-associated retinopathy, which generally follows an autosomal recessive inheritance pattern and is a frequent cause of macular degeneration in childhood. ABCA4 displays significant allelic heterogeneity whereby different mutations can cause retinal diseases with varying severity and age of onset. A genotype-phenotype model has been proposed linking ABCA4 mutations, purported ABCA4 functional protein activity and severity of disease, as measured by degree of visual loss and the age of onset. It has, however, been difficult to verify this model statistically in observational studies, as the number of individuals sharing any particular mutation combination is typically low. Seven founder mutations have been identified in a large number of Caucasian Afrikaner patients in South Africa, making it possible to test the genotype-phenotype model. A generalised linear model was developed to predict and assess the relative pathogenic contribution of the seven mutations to the age of onset of Stargardt disease. It is shown that the pathogenicity of an individual mutation can differ significantly depending on the genetic context in which it occurs. The results reported here may be used to identify suitable candidates for inclusion in clinical trials, as well as guide the genetic counselling of affected individuals and families.

Integrating HIV care into nurse-led primary health care services in South Africa: a synthesis of three linked qualitative studies

BackgroundThe integration of HIV care into primary care services is one of the strategies proposed to increase access to treatment for people living with HIV/AIDS in high HIV burden countries. However, how best to do this is poorly understood. This study documents different factors influencing models of integration within clinics.MethodsUsing methods based on the meta-ethnographic approach, we synthesised the findings from three qualitative studies of the factors that influenced integration of HIV care into all consultations in primary care. The studies were conducted amongst staff and patients in South Africa during a randomised trial of nurse initiation of antiretroviral therapy (ART) and integration of HIV care into primary care services – the Streamlining Tasks and Roles to Expand Treatment and Care for HIV (STRETCH) trial. Themes from each study were identified and translated into each other to develop categories and sub-categories and then to inform higher level interpretations of the synthesised data.ResultsClinics varied as to how HIV care was integrated. Existing administration systems, workload and support staff shortages tended to hinder integration. Nurses’ wanted to be involved in providing HIV care and yet also expressed preferences for developing expertise in certain areas and for establishing good nurse patient relationships by specialising in certain services. Patients, in turn, were concerned about the stigma of separate HIV services and yet preferred to be seen by nurses with expertise in HIV care. These factors had conflicting effects on efforts to integrate HIV care.ConclusionLocal clinic factors and nurse and patient preferences in relation to care delivery should be taken into account in programmes to integrate HIV care into primary care services. The integration of medical records, monitoring and reporting systems would support clinic based efforts to integrate HIV care into primary care services.

Predictors of tuberculosis (TB) and antiretroviral (ARV) medication non-adherence in public primary care patients in South Africa: a cross sectional study

BackgroundDespite the downward trend in the absolute number of tuberculosis (TB) cases since 2006 and the fall in the incidence rates since 2001, the burden of disease caused by TB remains a global health challenge. The co-infection between TB and HIV adds to this disease burden. TB is completely curable through the intake of a strict anti-TB drug treatment regimen which requires an extremely high and consistent level of adherence.The aim of this study was to investigate factors associated with adherence to anti-TB and HIV treatment drugs.MethodsA cross-sectional survey method was used. Three study districts (14 primary health care facilities in each) were selected on the basis of the highest TB caseload per clinic. All new TB and new TB retreatment patients were consecutively screened within one month of anti-tuberculosis treatment. The sample comprised of 3107 TB patients who had been on treatment for at least three weeks and a sub-sample of the total sample were on both anti-TB treatment and anti-retro-viral therapy(ART) (N = 757). Data collection tools included: a Socio-Demographic Questionnaire; a Post-Traumatic-Stress-Disorder (PTSD) Screen; a Psychological Distress Scale; the Alcohol Use Disorder Identification Test (AUDIT); and self-report measures of tobacco use, perceived health status and adherence to anti-TB drugs and ART.ResultsThe majority of the participants (N = 3107) were new TB cases with a 55.9% HIV co-infection rate in this adult male and female sample 18 years and older. Significant predictors of non-adherence common to both anti-TB drugs and to dual therapy (ART and anti-TB drugs) included poverty, having one or more co-morbid health condition, being a high risk for alcohol mis-use and a partner who is HIV positive. An additional predictor for non-adherence to anti-TB drugs was tobacco use.ConclusionsA comprehensive treatment programme addressing poverty, alcohol mis-use, tobacco use and psycho-social counseling is indicated for TB patients (with and without HIV). The treatment care package needs to involve not only the health sector but other relevant government sectors, such as social development.

Serious Treatment Related Adverse Drug Reactions amongst Anti-Retroviral Naïve MDR-TB Patients

BackgroundGlobally treatment outcomes for multidrug-resistant Mycobacterium tuberculosis (MDR-TB) remain poor and this is compounded by high drug toxicity. Little is known about the influence of adverse drug reactions (ADRs) on treatment outcomes in South Africa.MethodsWe evaluated the impact of severe ADRs among a prospective cohort of MDR-TB patients in South Africa (2000–2004). The HIV-infected study participants were anti-retroviral naïve.ResultsOf 2,079 patients enrolled, 1,390 (66.8%) were included in this analysis based on known HIV test results (39.1% HIV-infected). At least one severe ADR was reported in 83 (6.9%) patients with ototoxicity being the most frequent ADR experienced (38.9%).ConclusionsWe found that being HIV-infected but antiretroviral naïve did not increase occurrence of SADRs in patients on second-line anti-tuberculosis drugs. Early screening and proactive management of ADRs in this patient population is essential, especially given the rollout of decentralized care and the potential for overlapping toxicity of concomitant MDR-TB and HIV treatment.

Clinical practice guidelines for management of neuropathic pain: expert panel recommendations for South Africa

Neuropathic pain (NeuP) is challenging to diagnose and manage, despite ongoing improved understanding of the underlying mechanisms. Many patients do not respond satisfactorily to existing treatments. There are no published guidelines for diagnosis or management of NeuP in South Africa. A multidisciplinary expert panel critically reviewed available evidence to provide consensus recommendations for diagnosis and management of NeuP in South Africa. Following accurate diagnosis of NeuP, pregabalin, gabapentin, low-dose tricyclic antidepressants (e.g. amitriptyline) and serotonin norepinephrine reuptake inhibitors (duloxetine and venlafaxine) are all recommended as first-line options for the treatment of peripheral NeuP. If the response is insufficient after 2 - 4 weeks, the recommended next step is to switch to a different class, or combine different classes of agent. Opioids should be reserved for use later in the treatment pathway, if switching drugs and combination therapy fails. For central NeuP, pregabalin or amitriptyline are recommended as first-line agents. Companion treatments (cognitive behavioural therapy and physical therapy) should be administered as part of a multidisciplinary approach. Dorsal root entry zone rhizotomy (DREZ) is not recommended to treat NeuP. Given the large population of HIV/AIDS patients in South Africa, and the paucity of positive efficacy data for its management, research in the form of randomised controlled trials in painful HIV-associated sensory neuropathy (HIV-SN) must be prioritised in this country.

The Potential Cost and Benefits of Raltegravir in Simplified Second-Line Therapy among HIV Infected Patients in Nigeria and South Africa

BackgroundThere is an urgent need to improve the evidence base for provision of second-line antiretroviral therapy (ART) following first-line virological failure. This is particularly the case in Sub-Saharan Africa where 70% of all people living with HIV/AIDS (PHA) reside. The aim of this study was to simulate the potential risks and benefits of treatment simplification in second-line therapy compared to the current standard of care (SOC) in a lower-middle income and an upper-middle income country in Sub-Saharan Africa.MethodsWe developed a microsimulation model to compare outcomes associated with reducing treatment discontinuations between current SOC for second-line therapy in South Africa and Nigeria and an alternative regimen: ritonavir-boosted lopinavir (LPV/r) combined with raltegravir (RAL). We used published studies and collaborating sites to estimate efficacy, adverse effect and cost. Model outcomes were reported as incremental cost effectiveness ratios (ICERs) in 2011 USD per quality adjusted life year ($/QALY) gained.ResultsReducing treatment discontinuations with LPV/r+RAL resulted in an additional 0.4 discounted QALYs and increased the undiscounted life expectancy by 0.8 years per person compared to the current SOC. The average incremental cost was $6,525 per treated patient in Nigeria and $4,409 per treated patient in South Africa. The cost-effectiveness ratios were $16,302/QALY gained and $11,085/QALY gained for Nigeria and South Africa, respectively. Our results were sensitive to the probability of ART discontinuation and the unit cost for RAL.ConclusionsThe combination of raltegravir and ritonavir-boosted lopinavir was projected to be cost-effective in South Africa. However, at its current price, it is unlikely to be cost-effective in Nigeria.

Completeness and concordance of TB and HIV surveillance systems for TB-HIV co-infected patients in South Africa

South Africa currently maintains separate surveillance systems for tuberculosis (TB) and human immunodeficiency virus (HIV). There are future plans for integration of these systems; however, the consistency of information across the existing systems has not previously been assessed. To determine the completeness and concordance of data in the TB and HIV surveillance systems for TB-HIV co-infected patients. In a retrospective cohort evaluation of the records of TB-HIV co-infected patients in the Eden District of the Western Cape, data were abstracted from paper-based and electronic TB and HIV surveillance sources. Concordance was measured using Fleiss' kappa coefficient. Demographic variables had high completeness and concordance across the TB and HIV systems. Completeness and concordance for clinical variables was somewhat lower, particularly for TB variables in the HIV systems and HIV variables in the TB systems. Varying levels of completeness and concordance of surveillance data for TB-HIV co-infected patients highlight challenges in the current TB and HIV surveillance systems. Future integration of TB and HIV programs in this region will need to support more accurate data collection at all levels.

A Pilot Study Assessing the Impact of a Fortified Supplementary Food on the Health and Well-Being of Crèche Children and Adult TB Patients in South Africa

The South African population faces many of the global concerns relating to micronutrient deficiency and the impact this has on health and well-being. Moreover, there is a high prevalence of HIV infection, compounded by a high level of co-infection with TB.This pilot study evaluates the impact of a fortified supplementary food on the health and well-being of a cohort of crèche children, aged 3 to 6, and adult TB patients drawn from the Presidential Node of Alexandra, Johannesburg, South Africa. A further aim of this study was to evaluate the sensitivity and validity of non-invasive indicators of nutritional status in a field-based population sample.The investigational product, e’Pap, is supported by extensive anecdotal evidence that whole grain cereals with food-style nutrients constitute an effective supplementary food for those suffering from the effects of food insecurity, poor health and well-being, and coping with TB and HIV infection.The results indicate a beneficial effect of e’Pap for both study populations, and particularly for adult TB patients, whose baseline data reflected severe food insecurity and malnutrition in the majority of cases. There is evidence to suggest statistically significant improvements in key micronutrient levels, well-being and energy, hand-grip strength, the Bioelectrical Impedance Analysis (BIA) Illness Marker, and certain clinical indicators. Although Body Mass Index (BMI) and Mid Upper Arm Circumference (MUAC) are frequently used as standard measures to evaluate the efficacy of nutritional interventions, these indicators were not sufficiently sensitive in this study. Nor does weight gain necessarily indicate improved nutritional status. Hand-grip strength, lean body mass, and the BIA Illness Marker seem to be more useful indicators of change in nutritional status.

Health-related quality of life in patients on hemodialysis and peritoneal dialysis

Chronic kidney disease (CKD) is a worldwide public health problem, and its treatment imposes a considerable burden on patients and their families. Limitations in everyday activity may worsen the situation and affect the health-related quality of life (HRQOL) of patients with CKD. There are no studies on the HRQOL of dialysis patients in South Africa. We assessed the HRQOL of patients undergoing hemodialysis (HD) and continuous ambulatory peritoneal dialysis (PD) attending the Groote Schuur Hospital renal unit by using the Kidney Disease Quality of Life-Short Form version 1.3 questionnaire. Baseline demographic and clinical details of the participants were recorded. Analysis was performed (unpaired t test and univariate analysis) to compare the HRQOL between HD and PD patients and to identify factors influencing HRQOL. The HRQOL was low but not significantly different between HD and PD patients. In PD patients, the use of erythropoiesis-stimulating agents (ESA) significantly contributed to the emotional well-being (r 2 = 0.267; P = 0.01) and alleviation of pain (r 2 = 0.073; P = 0.049); in HD patients also, ESA use was associated with emotional well-being (r 2 = 0.258; P <0.0001) as well as improvement in energy/fatigue (r 2 = 0.390; P <0.0001). Systolic and diastolic blood pressures significantly influenced cognitive function in PD patients (P <0.05). Parathyroid hormone level significantly influenced the physical functioning and energy/fatigue domains in HD patients (P <0.0001). Serum ferritin (r 2 = 0.441; P = 0.002) and level of hemoglobin concentration (r 2 = 0.180; P = 0.006) were significantly associated with the domain role emotional in PD and HD patients, respectively. Although HRQOL is low in dialysis patients in Cape Town, the factors that have been identified to be associated with these scores (such as anemia and hyperparathyroidism) if aggressively managed and corrected may assist in improving patients' HRQOL.

Risk of Death among HIV Co-Infected Multidrug Resistant Tuberculosis Patients, Compared To Mortality in the General Population of South Africa.

Even though highly effective drugs are available in South Africa, multidrug resistant tuberculosis (MDR-TB) patients with HIV infection have higher mortality compared to HIV-uninfected MDR-TB patients. This trend has been observed in similar countries with high HIV prevalence. This study sought to determine excess mortality attributable to HIV among MDR-TB patients in South Africa using relative survival methods. Data available were from a cohort of 2079 MDR-TB patients enrolled in a Standardized Programmatic Management of MDR-TB from 2000 to 2004 in South Africa. A Poisson-based model adjusted for age, gender, year of diagnosis, TB history, and resistance to ethambutol, anti-TB injectable drugs and fluoroquinolones antibiotics was constructed to assess the excess mortality among HIV co-infected MDR-TB patients. Excess hazard ratios (EHRs) were used to describe the effect of the predictors on net mortality, controlling for the general mortality in the South African population. Death was recorded on 1619 patients, of whom 367 (22.7%) had died within 2 years. Out of the 1413 patients that tested for HIV infection, 554 (39.2%) tested positive. Excess mortality was higher in HIV infected, compared to HIV uninfected, MDR-TB patients (adjusted excess hazard ratio, 5.6 [95% CI, 3.2-9.7]); in patients whose TB isolates' resistance to ethambutol and kanamycin was unknown (3.7 [2.1-6.2] and 4.87 [1.9-13.3], respectively) vs. known. There were no differences in excess mortality between age and gender of the patient, year of diagnosis and TB history. Adjusting for some important predictors, MDR-TB patients with HIV infection experienced higher excess mortality compared to HIV-uninfected MDR-TB patients, after accounting for the general mortality in South Africa. An appropriate, though complex method has produced predictor effect estimates similar to those obtained from classical methods. Thus, the use of relative survival methods should be encouraged in the analysis of causespecific mortality, when ascertainment of cause of death is inaccurate or unknown.

The Clinical and Economic Impact of Genotype Testing at First-line Antiretroviral Therapy Failure for HIV-Infected Patients in South Africa

In resource-limited settings, genotype testing at virologic failure on first-line antiretroviral therapy (ART) may identify patients with wild-type (WT) virus. After adherence counseling, these patients may safely and effectively continue first-line ART, thereby delaying more expensive second-line ART. We used the Cost-Effectiveness of Preventing AIDS Complications International model of human immunodeficiency virus (HIV) disease to simulate a South African cohort of HIV-infected adults at first-line ART failure. Two strategies were examined: no genotype vs genotype, assuming availability of protease inhibitor-based second-line ART. Model inputs at first-line ART failure were mean age 38 years, mean CD4 173/µL, and WT virus prevalence 20%; genotype cost was $300 per test and delay to results, 3 months. Outcomes included life expectancy, per-person costs (2010 US dollars), and incremental cost-effectiveness ratios (dollars per years of life saved [YLS]). No genotype had a projected life expectancy of 106.1 months, which with genotype increased to 108.3 months. Per-person discounted lifetime costs were $16 360 and $16 540, respectively. Compared to no genotype, genotype was very cost-effective, by international guidance, at $900/YLS. The cost-effectiveness of genotype was sensitive to prevalence of WT virus (very cost-effective when prevalence ≥ 12%), CD4 at first-line ART failure, and ART efficacy. Genotype-associated delays in care ≥ 5 months decreased survival and made no genotype the preferred strategy. When the test cost was <$100, genotype became cost-saving. Genotype resistance testing at first-line ART failure is very cost-effective in South Africa. The cost-effectiveness of this strategy will depend on prevalence of WT virus and timely response to genotype results.

Tuberculosis patients in South Africa have a high prevalence of psychological distress

Question: What are the prevalence and predictors of psychological distress in people with tuberculosis in South Africa? Population: In total 4935 patients, aged between 18 and 93 years, within 1...

Detectable Changes in The Blood Transcriptome Are Present after Two Weeks of Antituberculosis Therapy

RationaleGlobally there are approximately 9 million new active tuberculosis cases and 1.4 million deaths annually. Effective antituberculosis treatment monitoring is difficult as there are no existing biomarkers of poor adherence or inadequate treatment earlier than 2 months after treatment initiation. Inadequate treatment leads to worsening disease, disease transmission and drug resistance.ObjectivesTo determine if blood transcriptional signatures change in response to antituberculosis treatment and could act as early biomarkers of a successful response.MethodsBlood transcriptional profiles of untreated active tuberculosis patients in South Africa were analysed before, during (2 weeks and 2 months), at the end of (6 months) and after (12 months) antituberculosis treatment, and compared to individuals with latent tuberculosis. An active-tuberculosis transcriptional signature and a specific treatment-response transcriptional signature were derived. The specific treatment response transcriptional signature was tested in two independent cohorts. Two quantitative scoring algorithms were applied to measure the changes in the transcriptional response. The most significantly represented pathways were determined using Ingenuity Pathway Analysis.ResultsAn active tuberculosis 664-transcript signature and a treatment specific 320-transcript signature significantly diminished after 2 weeks of treatment in all cohorts, and continued to diminish until 6 months. The transcriptional response to treatment could be individually measured in each patient.ConclusionsSignificant changes in the transcriptional signatures measured by blood tests were readily detectable just 2 weeks after treatment initiation. These findings suggest that blood transcriptional signatures could be used as early surrogate biomarkers of successful treatment response.

Prevalence and associations with hepatitis B and hepatitis C infection among HIV-infected adults in South Africa

We assessed prevalence and factors associated with hepatitis B in a cross section of HIV-infected primary care and antinatal clinic patients in South Africa and evaluated a rapid hepatitis B surface antigen (HBsAg) assay. We enrolled 998 patients; 88% were women, median age was 29 years and median CD4 count was 354 cells/mm(3). HBsAg enzyme-linked immunosorbent assay (ELISA), anti-hepatitis B core (HBc) antibodies and hepatitis C virus antibody were positive among 4.2%, 37% and 0.1% of subjects, respectively. Univariate and multivariate associations were assessed using logistic regression. Anti-HBc antibodies were associated with alcohol use, traditional medicines and higher CD4 counts; HBsAg positivity was associated with lower CD4. Compared with the HBsAg ELISA, a rapid HBsAg test had a sensitivity of 75.0% and specificity of 99.6%. In conclusion, we identified a moderate prevalence of both HBsAg and anti-HBc. Importantly, we found that subjects with HBsAg positivity had lower CD4 counts.

Factors influencing the development of early- or late-onset Parkinson’s disease in a cohort of South African patients

Neurodegenerative disorders such as Parkinson's disease (PD) contribute significantly to global disease burden. PD can be categorised into early-onset PD (EOPD) with an age at onset (AAO) of ≤50 years and late-onset PD (LOPD) with an AAO of 50 years. To identify factors influencing EOPD and LOPD development in a group of patients in South Africa (SA). A total of 397 unrelated PD patients were recruited from the Movement Disorders Clinic at Tygerberg Hospital and via the Parkinson's Association of SA. Patient demographic and environmental data were recorded and associations with PD onset (EOPD v. LOPD) were analysed with a Pearson's Chi-squared test. The English- and Afrikaans-speaking (Afrikaner) white patients were analysed separately. Logistic regression analysis showed that ethnicity (p<0.001) and family history (p=0.004) were independently associated with AAO of PD. Average AAO was younger in black, coloured and Afrikaner patients than English-speaking white patients. A positive family history of PD, seen in 31.1% of LOPD patients, was associated with a younger AAO in the study population. These associations may be attributed to specific genetic and/or environmental risk factors that increase PD susceptibility and influence the clinical course of the disorder. More studies on PD in the unique SA populations are required to provide novel insights into mechanisms underlying this debilitating condition.

Hazardous and Harmful Alcohol Use and Associated Factors in Tuberculosis Public Primary Care Patients in South Africa

The aim of this study was to assess the prevalence of hazardous and harmful alcohol use and associated factors among patients with tuberculosis in South Africa. In a cross-sectional survey new tuberculosis (TB) and TB retreatment patients were consecutively screened using the Alcohol Use Disorder Identification Test (AUDIT) within one month of anti-tuberculosis treatment. The sample included 4,900 (54.5% men and women 45.5%) tuberculosis patients from 42 primary care clinics in three districts. Results indicate that, overall 23.2% of the patients were hazardous or harmful alcohol drinkers, 31.8% of men and 13.0% of women were found to be hazardous drinkers, and 9.3% of men and 3.4% of women meet criteria for probable alcohol dependence (harmful drinking) as defined by the AUDIT. Men had significantly higher AUDIT scores than women. In multivariable analyses it was found that among men poor perceived health status, tobacco use, psychological distress, being a TB retreatment patient and not being on antiretroviral therapy (ART), and among women lower education, tobacco use and being a TB retreatment patient were associated with hazardous or harmful alcohol use. The study found a high prevalence of hazardous or harmful alcohol use among tuberculosis primary care patients. This calls for screening and brief intervention and a comprehensive alcohol treatment programme as a key component of TB management in South Africa.

Assessing the impact of prevalent tuberculosis on mortality among antiretroviral treatment initiators

Westreich and colleagues reported on the association between treatment for pulmonary tuberculosis (TB) at baseline in a South African antiretroviral treatment (ART) programme and subsequent mortality risk [1,2]. Although patients receiving TB treatment had higher all-cause mortality risk compared to those not treated, no such association was observed after adjustment for baseline CD4 count, other patient variables and loss to follow-up (hazard ratio,1.06; 95%CI 0.75–1.49) [2]. This finding was robust when additional death registry data were included and follow-up was extended by 18 months [1]. This finding seems counter-intuitive and we are concerned that some might conclude from these studies that strategies to reduce the burden of TB in ART programmes in sub-Saharan Africa are not important with regard to addressing the high mortality in ART programmes in the region. TB is one of the most frequently reported causes of death in this clinical setting [3]. Post-mortem studies conducted in Africa (both before and during the ART era) have reported that approximately 30%–50% of hospital in-patients who died of HIV/AIDS have evidence of active TB, which was often disseminated [4–7]. TB was also identified post-mortem in a high proportion of patients in South Africa who died while receiving ART [8]. It must be noted that much disease identified in these studies was undiagnosed at the time of death. Despite careful statistical analyses and consideration of various potential biases, Westreich and colleagues have not addressed the fundamental issue as to whether patients in their study were accurately classified as having TB or not. This was defined simply on the basis of whether or not they were receiving treatment for pulmonary TB [2]. No case definition for TB disease was used, no microbiological data were presented and extrapulmonary TB was not accounted for. The disease-free comparator group was simply defined as patients not receiving treatment for pulmonary TB. No systematic microbiological screening of patients was done at baseline to rule-out TB and post-mortems were not done to assess for unascertained TB in patients who died in the TB-free group. Moreover, patients developing incident disease during the initial weeks of ART were not excluded from the TB-free group. Diagnosis of TB in this clinical setting in Africa is challenging due to the non-specific clinical presentation, high rates of sputum smear-negative, extrapulmonary and disseminated disease and co-morbidity that may mimic TB [9,10]. Since widely used diagnostic tools (sputum smear microscopy and chest radiology) are so blunt and culture is very slow and much less used, there is considerable under-diagnosis as well as some over-diagnosis of TB. Much incident disease diagnosed in the first weeks of ART is actually disease that was present at baseline but missed during screening [11,12]. In studies in which patients enrolling in South African ART clinics who have no pre-existing TB diagnosis are intensively screened for TB at baseline regardless of the presence of absence of symptoms, approximately 15%–25% have sputum culture-positive pulmonary TB [13–15]. Potential misclassification of patients into diseased and disease-free groups may substantially undermine the validity of the findings of Westreich and colleagues. We agree with Straetemans and colleagues that currently available data on TB as a risk factor for mortality in ART programmes are insufficient to draw definite conclusions as they have considerable limitations [16]. We suspect that TB (especially undiagnosed disease) is a key factor contributing to high early mortality and that strategies to address this should include rapid microbiological screening of all patients regardless of clinical symptoms [9,15,17]. Further well designed studies are therefore needed and accurate disease ascertainment will be essential for these to be interpretable.