Cardiovascular toxicity of contemporary antiretroviral therapy.

PURPOSE OF REVIEW: HIV treatment has evolved since the introduction of antiretroviral therapy (ART) in the 1990s. Earlier treatment strategies, and the introduction of integrase inhibitors in preferred first-line ART have fundamentally changed cardiovascular side effects due to HIV infection and ART. This review provides an update on cardiovascular toxicity of contemporary ART. RECENT FINDINGS: Cardiovascular disease (CVD) risk, including heart failure, is still increased in people living with HIV (PLWH). Exposure to older antiretrovirals, including stavudine and zidovudine, still impact on CVD risk through persistent changes in body fat distribution years after discontinuation. Protease inhibitors (PI) and efavirenz have associated metabolic disturbances and increased risk of CVD, although use is decreasing worldwide. Integrase inhibitors and CCR5 antagonists seem to have negligible immediate CVD toxicity. Weight gain on newer antiretrovirals including integrase inhibitors is a reason for concern. SUMMARY: CVD risk should be monitored carefully in PLWH who were exposed to first generation ART, efavirenz or to PIs. Registries should capture ART use and CVD events to stay informed on actual clinical risk in the current era of rapid initiation on integrase inhibitor-based ART.

COVID-19 vaccines - less obfuscation, more transparency and action.

Letter by Venter et al. on editorial  by Schoub (Dial down the rhetoric over COVID-19 vaccines. S Afr Med J 2021;111(6):522-523. https://doi.org/10.7196/SAMJ.2021.v111i6.15740).

The readability of informed consent forms for research studies conducted in South Africa.

BACKGROUND: Informed consent forms (ICFs) are used to obtain consent from participants. However the complexity and comprehensiveness of these forms may not be appropriate. Readability can be quantified by formulas in Microsoft (MS) Word, such as the Flesch Reading Ease test. The South African (SA) ethics guidelines suggest that the MS Word Flesch-Kincaid Reading Grade score should be used to assess the complexity of ICFs and should be the equivalent of grade 8 level, or lower. OBJECTIVES: To use readability formulas to determine whether current SA ICFs are appropriate for the general population. METHODS: This was a descriptive study of a sample of English ICFs (solicited from our studies, as well as from local researchers) which received approval from local ethical review boards during the past 5 years, for prospective (≥6 months) drug studies that explored treatment and prevention of HIV, tuberculosis, diabetes or cardiovascular disease. ICFs were evaluated in MS Word for Flesch Reading Ease and Flesch-Kincaid Reading Grade, with the Simple Measure of Gobbledygook (SMOG) index calculated using www.readabilityformulas.com. Recommended targets for easy readability are above 60 for the Flesch Reading Ease score, and less than or equal to a grade 8 reading level for the Flesch-Kincaid Reading Grade and SMOG. RESULTS:   A total of 75 consent forms from 35 individual research studies conducted in SA over the last 5 years were included. The consent forms had been approved by six ethics committees across seven of the SA provinces. The median (interquartile range (IQR)) Flesch Reading Ease score was 55.8 (48.7 - 59.7) and 18 (25.0%) of the ICFs had easy or standard readability, while the median (IQR) Flesch-Kincaid Grade was 10.2 (8.8 - 11.4), with 23 (30.6%) at least a grade 8 level or lower. The median (IQR) SMOG index was 9.8 (9.0 - 11.1) and 4 (5.3%) scored below grade 8 level. CONCLUSIONS: Two-thirds of the ICFs from this study fail to meet the SA readability standard, a result matched by using alternative readability formulas. Readability can be improved with simple techniques and by actively monitoring readability metrics.

Antiretroviral therapy non-adherence among HIV-positive patients presenting to an emergency department in Johannesburg, South Africa: Associations and reasons.

BACKGROUND: Suboptimal antiretroviral therapy (ART) adherence is associated with viral resistance, opportunistic infections and increased mortality. OBJECTIVES: To determine the rates of ART non-adherence and its associations, and also the reasons for ART non-adherence, among HIV-positive patients presenting to a major central hospital emergency department (ED). METHODS: Consecutive HIV-positive patients presenting to the Charlotte Maxeke Johannesburg Academic Hospital adult ED between 7 July 2017 and 18 October 2018 were prospectively enrolled. Self-reported adherence was assessed using the AIDS Clinical Trials Group Adherence Questionnaire (ACTG-AQ). RESULTS: Of the 1 224 consecutive HIV-positive participants enrolled, 761 (75.2%) were on ART at the time of ED presentation. Of these, 245 (32.2%) were non-adherent as per the ACTG-AQ. Participants not yet on ART prior to ED presentation had significantly higher in-hospital mortality than participants on ART (odds ratio 1.69; 95% confidence interval 1.21 - 2.34; p=0.002). Younger age, male sex, CD4 count <100 cells/µL, lack of viral suppression, a high National Early Warning Score 2 (≥7 points) and length of hospital stay ≥7 days were significantly associated with ART non-adherence (p<0.05). Forgetfulness (13.9%) and lack of social support, depression/stress/mental illness, and lack of money for transport to collect medications (9.9% each) were the most common reasons given for ART non-adherence. CONCLUSIONS: Of HIV-positive patients presenting to the ED, a high proportion were either not yet initiated on ART or ART non-adherent. HIV programmes should focus on HIV-positive ED attendees with the aim of identifying high-risk patients and providing adequate ART adherence support.

Ideal Cardiovascular Health Index and Its Determinants in a Rural South African Population.

Background: The ideal cardiovascular health index (CVHI) is a measure to summarize cardiovascular (CV) health, and includes smoking, body-mass index, physical activity, blood pressure, glucose, total cholesterol, and diet. Objective: This study aimed to assess CV health using the CVHI and determinants on CV health in a rural African population, and correlate carotid intima-media thickness (CIMT), a surrogate marker for atherosclerosis, with CVHI. Methods: A cross-sectional analysis was performed on baseline data of the Ndlovu Cohort Study, located in rural South Africa. CVHI score (CVHIs) was calculated by the sum of favourable CVHI factors (range 0 to 7). Logistic regression was performed to examine the association of age, sex, HIV-status, education level, employment status, and income with good CV health (5-7 favourable health factors). Mean CIMT was displayed by poor, intermediate and good CV health. Results: The study included 1927 participants with a mean age of 38.7 years (SD ± 12.8). Of the factors contributing to the CVHI, glucose and total cholesterol scored best; diet least good. Average CVHIs for the population was 4.4 (SD ± 1.2) and 53% of the population had a good CV health. Determinants associated with good CV health were younger age, higher educational attainment, and HIV positivity. CVHIs showed good agreement with CIMT. Conclusion: CVHIs showed that more than half of the participants had a good CV health. Agreement between CVHIs and CIMT indicates potential use of CVHIs as a surrogate marker for CV risk. The study highlights the importance of education for health promotion; good CV health in HIV-positive participants may in part be attributed to more frequent health care contact and provision of chronic disease care. Highlights: Good cardiovascular health (CVH) was observed in 53% of the study population.In global comparison, rural African study participants showed a good CVH score.HIV positivity was associated with a good CVH score.CVH score showed good agreement with carotid intima-media thickness.

Cardiovascular disease risk and its determinants in people living with HIV across different settings in South Africa.

OBJECTIVES: Socio-economic factors and lifestyle are known to differ across geographies and populations, which may result in distinct risk profiles for cardiovascular disease (CVD). This study assessed carotid intima-media thickness (CIMT), a proxy for CVD, and its determinants in two groups of people living with HIV (PLHIV) in two different settings in South Africa. METHODS: A cross-sectional analysis was conducted comparing data from the Ndlovu Cohort Study in the Limpopo Province (group 1) and from three clinical trials in Johannesburg (group 2). The association between demographics, conventional CVD risk factors, HIV-related factors and CIMT in groups 1 and 2 was analysed with two separate multivariable linear regression models. RESULTS: Group 1 consisted of 826 participants (mean age 42.2 years) and mean (± standard deviation) CIMT was 0.626 ± 0.128 mm. In this group, sex, age, body mass index (BMI), cholesterol, glucose and antiretroviral therapy (ART) duration (ß = 0.011 mm per 5 years; P = 0.02) were associated with higher CIMT. There were positive interactions between age and ART duration and age and cholesterol. Group 2 consisted of 382 participants (mean age 39.5 years) and mean (± standard deviation) CIMT was 0.560 ± 0.092 mm. In this group, only sex, education level, BMI and cholesterol were associated with higher CIMT, albeit with weaker associations than in group 1. CONCLUSIONS: Conventional CVD risk factors were the main drivers of CIMT. The impact of some of these risk factors appeared to increase with age. Differences in sample size, age and viral suppression might explain why an effect of ART was observed in group 1 but not in group 2.

Descriptive analysis of World Health Organization-recommended second-line antiretroviral treatment: A retrospective cohort data analysis.

BACKGROUND: World Health Organization guidelines recommend that HIV patients who do not achieve viral suppression on efavirenz-based first-line antiretroviral therapy (ART) should be changed to a protease inhibitor (PI)-based regimen. In South Africa (SA), ~200 000 people are on second-line treatment, but little is known about these patients. OBJECTIVES: To describe second-line black African patients in a large urban area. METHODS: A quantitative retrospective study of 825 second-line patients in central Johannesburg, SA (subdistrict F), was performed with data extracted from government databases. Demographic characteristics, treatment status and laboratory information were gathered, then analysed with CD4+ cell count, viral load (VL) and retention-in-care data as outcome variables. RESULTS: The average recorded time to VL measurement after the switch to a PI-based ART regimen was 20 months, and 83.1% (570/686) of patients with a recent VL achieved viral suppression while on second-line treatment. The most recent median CD4+ cell count for the cohort was 286 cells/µL (interquartile range 160 - 478), which represented a 177 cells/µL increase from the baseline count at the start of first-line ART. Slightly less than three-quarters (72.4%) of the population remained active in care in the study clinics from initiation on first-line ART. Demographic characteristics such as being <25 years of age, male sex and geographical transfer (started initial treatment in a different region) independently predicted low CD4+ cell counts and virological failure on second-line treatment. Patients with virological failure were most likely (odds ratio (OR) 3.13, 95% confidence interval (CI) 1.50 - 6.56) to be lost to follow-up after the switch, while patients from Hillbrow Community Health Centre (OR 0.27, 95% CI 0.16 - 0.44), South Rand Hospital (OR 0.24, 95% CI 0.12 - 0.47) and Jeppe Clinic (OR 0.38, 95% CI 0.16 - 0.88), three larger sites, were most likely to remain active in care. CONCLUSIONS: VL suppression was high in patients on second-line treatment, but one-fifth of patients were lost to follow-up. Younger age, male sex and transfer from other treatment sites predicted poor treatment outcomes, highlighting opportunities for prioritisation of adherence interventions.

Improved simplified clinical algorithm for identifying patients eligible for immediate initiation of antiretroviral therapy for HIV (SLATE II): protocol for a randomized evaluation.

BACKGROUND: The World Health Organization recommends rapid (≤ 7 days) or same-day initiation of antiretroviral treatment (ART) for HIV-positive patients. South Africa adopted this recommendation in 2017, but multiple clinic visits, long waiting times, and delays for laboratory tests remain common. Streamlined approaches to same-day initiation that allow the majority of patients to start ART immediately, while ensuring that patients who do require additional services receive them, are needed to achieve national and international treatment program goals. METHODS/DESIGN: The SLATE II (Simplified Algorithm for Treatment Eligibility) study is an individually randomized evaluation of a clinical algorithm to reliably determine a patient's eligibility for immediate ART initiation without waiting for laboratory results or additional clinic visits. It differs from the earlier SLATE I study in management of patients with symptoms of tuberculosis (under SLATE II these patients may be started on ART immediately) and other criteria for immediate initiation. SLATE II will randomize (1:1) 600 adult, HIV-positive patients who present for HIV testing or care and are not yet on ART in South Africa. Patients randomized to the standard arm will receive standard-of-care ART initiation from clinic staff. Patients randomized to the intervention arm will be administered a symptom report, medical history, brief physical exam, and readiness assessment. Symptomatic patients will also have a tuberculosis (TB) module with lipoarabinomannan antigen of mycobacteria test. Patients who have satisfactory results for all four components will be dispensed antiretrovirals (ARVs) immediately, at the same clinic visit. Patients who have any negative results will be referred for further investigation, care, counseling, tests, or other services prior to being dispensed ARVs. Follow-up will be by passive medical record review. The primary outcomes will be ART initiation in  ≤ 7 days and retention in care 8 months after study enrollment. DISCUSSION: SLATE II improves upon the SLATE I study by reducing the number of reasons for delaying ART initiation and allowing more patients with TB symptoms to start ART on the day of diagnosis. If successful, SLATE II will provide a simple and streamlined approach that can readily be adopted in other settings without investment in additional technology. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03315013 . Registered on 19 October 2017.

Quality of counselling and support provided by the South African National AIDS Helpline: Content analysis of mystery client interviews.

BACKGROUND: Telephone helplines can facilitate referral, education and support for patients living with HIV or those concerned about the infection. The anonymity of helplines facilitates discussion of sensitive issues that are difficult to raise face to face. These services could support the expansion of HIV self-testing. However, maintaining quality and standardising messages in rapidly evolving fields such as HIV is challenging. OBJECTIVES: To evaluate the quality of the South African (SA) National AIDS Helpline. METHODS: Mystery clients posing as members of the public made 200 calls to the service in 2014. They presented several scenarios, including having received HIV-positive results from a doctor's secretary or through self-testing. Following the call, 'clients' completed a semistructured questionnaire on the information received and the caller-counsellor interaction. RESULTS: Calls were answered within a median of 5 seconds (interquartile range 2 - 14). Conversations took place in 8 of the 11 SA official languages, though mainly in English. Overall, 75% of callers felt that with the information they received they could locate a nearby clinic for further services. Counsellors expressed appropriate levels of concern about inadequate counselling that callers had received and confidentiality breaches in some scenarios. Eight counsellors incorrectly mentioned the need for a waiting period to confirm a positive result. Consistent with policy, almost all said that being foreign would not affect HIV treatment access. About 90% explained the need for CD4+ testing and antiretroviral therapy, but only 78% discussed HIV prevention. Counsellors were mostly empathetic (83%), though some adopted a neutral tone (10%) or were brusque (6%) or unhelpful (2%). CONCLUSIONS: Overall, helpline counsellors were proficient at providing information about local clinics, HIV testing and steps needed for initiating ART. Dissatisfaction with the caller-counsellor interactions, instances of incorrect information and the relatively low attention accorded to HIV prevention are worrying, however. Training for both refreshing and updating knowledge, and supervision and monitoring of calls, could target these areas.

Access to and utilisation of healthcare services by sex workers at truck-stop clinics in South Africa: A case study.

BACKGROUND: Sex worker-specific health services aim to respond to the challenges that this key population faces in accessing healthcare. These services aim to integrate primary healthcare (PHC) interventions, yet most services tend to focus on prevention of HIV and sexually transmitted infections (STIs). North Star Alliance (North Star) is a public-private partnership providing a healthcare service package in roadside wellness clinics (RWCs) to at-risk populations along transport corridors in sub-Saharan Africa. OBJECTIVES: To inform future service development for sex workers and describe North Star's contribution to healthcare provision to this population in South Africa, we describe services provided to and utilised by sex workers, and their views of these services. METHODS: Using a mixed-methods approach, we present quantitative analyses of anonymised North Star routine data for sex workers for October 2013 - September 2015, covering nine sites in seven provinces. Clinic visits were disaggregated by type of service accessed. We performed thematic analysis of 25 semi-structured interviews conducted at five clinics. RESULTS: A total of 2 794 sex workers accessed RWCs during the 2 years. Sex workers attending clinics were almost exclusively female (98.2%) and aged <40 years (83.8%). The majority were South African (83.8%), except at Musina, where the majority of clients were Zimbabwean. On average, sex workers visited the clinics 1.5 times per person. However, in most cases only one service was accessed per visit. PHC services other than for HIV and STIs were accessed more commonly than HIV-specific services and STI treatment. There was an increase in the number of services accessed over time, the figure almost doubling from 1 489 during the first year to 2 936 during the second year. Although during recruitment participants reported having had sex in exchange for goods or money during the past 3 months, not all participants self-identified as sex workers during interviews; however, all reported feeling at higher risk of poor health than the general population owing to their involvement in sex work. Participants reported satisfaction with site accessibility, location and operating hours. Sex workers accessing sites described services as being suitable and accessible, with friendly staff. CONCLUSIONS: RWCs were highly appreciated by the users, as they are suitable and accessible. The sex workers who used the clinics visited them irregularly, mostly for PHC services other than HIV and STIs. Services other than the one for which the sex worker came to the clinic rarely appeared to be offered. We recommend areas for service expansion.

High incidence of latent tuberculous infection among South African health workers: an urgent call for action.

SETTING: In South Africa, health care workers (HCWs) are at two-fold greater risk of acquiring tuberculosis (TB) disease than the general population. Few studies have evaluated the risk of incident tuberculous infection. OBJECTIVE: To determine the incidence and risk factors for latent tuberculous infection (LTBI) among HCWs and to compare the results of the interferon-gamma release assay (IGRA) with those of the tuberculin skin test (TST). DESIGN: HCWs, including medical students, underwent a TST and human immunodeficiency virus (HIV) and IGRA testing at baseline and 12 months, and IGRA at 6 months. The participants kept 12-month TB exposure logs. RESULTS: Among 199 participants (150 [76%] females, median age 31 years [range 20-61]), incident LTBI was documented using IGRA in 25/97 (26%; incident rate 29 cases/100 person-years [py], 95%CI 20-44) and using TST in 25/93 (27%; incident rate 29 cases/100 py, 95%CI 19-42). Agreement between TST and IGRA was poor (44.8%, κ = 0.23). Higher annual exposure to TB cases was reported among persons with LTBI than in those who were persistently IGRA-negative (81 cases, 95%CI 61-102 vs. 50 cases, 95%CI 43-57, P < 0.01). CONCLUSION: The high LTBI incidence and the association of incident LTBI with annual TB caseload among HCWs indicate that more effective TB infection control should be implemented in South African health care facilities.

HIV testing in the critical care setting: views of patients, family members and health providers from urban South Africa.

As antiretroviral treatment has led to decreased morbidity, HIV testing policy has increasingly shifted towards routine, provider-initiated approaches. Yet, few studies have examined the acceptability of provider-initiated HIV testing in the intensive, or critical care setting, where knowledge of HIV status is likely to impact on clinical management but explicit consent for testing is difficult to obtain. We conducted qualitative research in an urban hospital and clinic in Johannesburg. In-depth interviews were conducted among HIV testing clients (n = 20), recently discharged critical care patients (n = 13) and family members of critical care patients (n = 14). One focus group discussion was held with health care providers (n = 10). HIV testing in critical care was viewed as acceptable but challenging to implement. An overarching theme of ambivalence emerged from patients and families, who saw HIV testing as a pre-requisite to appropriate clinical care, but were concerned about the quality of its delivery. While providers were aware of the current "no testing without consent" policy, they expressed frustration in cases when testing was in the patient's best interest but consent could not be obtained. Furthermore, providers found it stressful to weigh up patient confidentiality against medical necessity when assessing patients' "best interests". Without specific guidelines, they often developed pragmatic, ad hoc ways to resolve dilemmas around testing in critical care. Our findings suggest that HIV testing guidelines specific to the critical care setting may help providers do their jobs more ethically and transparently. Provider-initiated approaches are likely to be acceptable to patients and may improve clinical outcomes, but training and support in policy implementation and ethical decision-making are essential.

Should HIV be a notifiable disease? Old questions with some new arguments.

HIV notification enters national debate regularly, often introduced by politicians and supported by many individual healthcare workers. We argue that its proponents advance confused or poorly informed rationales for making HIV notifiable. We present reasons why making HIV notifiable would be inappropriate in South Africa, why the public health benefits of a notification programme are not even likely, and why there are risks of public health and human rights harms.

A brief history of South Africa's response to AIDS.

The story of the AIDS response in South Africa over the past 4 years is one of great progress after almost a decade of complex and tragic denialism that united the world and civil society in a way not seen since the opposition to apartheid. Today the country can boast > 2 million people on antiretroviral therapy, far and away the largest number in the world. Prevention efforts appear to be yielding results. The estimated number of annual new HIV infections declined by 79 000 between 2011 and 2012. New HIV infections among adults aged 15-49 years are projected to decline by 48% by 2016, from 414,000 (2010) to -215,000 (2016). The national incidence rate has reached its lowest level since the disease was first declared an epidemic in 1992, translating into reductions in both infant and under-5 mortality and an increase in life expectancy from 56 to 60 years over the period 2009-2011 alone. This is largely thanks to a civil society movement that was prepared to pose a rights-based challenge to a governing party in denial, and to brave health officials, politicians and clinicians working in a hostile system to bring about change.

Prevalence, risk factors and risk perception of tuberculosis infection among medical students and healthcare workers in Johannesburg, South Africa.

BACKGROUND: Tuberculin skin test (TST) and interferon gamma release assays (IGRAs) are both recommended for routine screening of healthcare workers (HCWs) in low tuberculosis (TB)-burden countries. More recently, based on scarce data, the World Health Organization strongly recommended that IGRA should not be used for occupational screening in high-burden settings. OBJECTIVE: To assess the prevalence of latent tuberculosis infection (LTBI) determined among highly exposed HCWs and low-exposed medical students in Johannesburg, South Africa. Methods. We performed a cross-sectional study using both TSTs and IGRAs to determine the prevalence rate of LTBI in 79 medical students and 120 HCWs providing HIV and/or TB care. RESULTS: The prevalence of LTBI among HCWs was 2- to 4-fold higher than that among medical students (56.7% v. 26.6% TST-positive; 69.2% v.15.2% IGRA-positive, respectively), with 3-fold higher odds for TST positivity and 12-fold higher odds for IGRA positivity among HCWs compared with students. Despite the perception of being at high risk, few HCWs protected themselves against LTBI. The majority of HCWs reported that they would participate in annual TST or IGRA screening. CONCLUSION: Infection control strategies and occupational screening programmes for professional and lay HCWs, as well as medical students, should be implemented in all high-burden settings. Further research is needed to determine whether IGRA or TST is the optimal assay for periodical screening of HCWs in high-burden settings.

North-South Corridor Demonstration Project: Ethical and Logistical Challenges in the Design of a Demonstration Study of Early Antiretroviral Treatment for Long Distance Truck Drivers along a Transport Corridor through South Africa, Zimbabwe, and Zambia.

Background. Long-distance truck drivers are at risk of acquiring and transmitting HIV and have suboptimal access to care. New HIV prevention strategies using antiretroviral drugs to reduce transmission risk (early antiretroviral therapy (ART) at CD4 count >350 cells/ µ L) have shown efficacy in clinical trials. Demonstration projects are needed to evaluate "real world" programme effectiveness. We present the protocol for a demonstration study to evaluate the feasibility, acceptability, and cost of an early ART intervention for HIV-positive truck drivers along a transport corridor across South Africa, Zimbabwe, and Zambia, as part of an enhanced strategy to improve treatment adherence and retention in care. Methods and Analysis. This demonstration study would follow an observational cohort of truck drivers receiving early treatment. Our mixed methods approach includes quantitative, qualitative, and economic analyses. Key ethical and logistical issues are discussed (i.e., choice of drug regimen, recruitment of participants, and monitoring of adherence, behavioural changes, and adverse events). Conclusion. Questions specific to the design of tailored early ART programmes are amenable to operational research approaches but present substantial ethical and logistical challenges. Addressing these in demonstration projects can inform policy decisions regarding strategies to reduce health inequalities in access to HIV prevention and treatment programmes.

Causes of death on antiretroviral therapy: a post-mortem study from South Africa.

BACKGROUND: Mortality in the first months of antiretroviral therapy (ART) is a significant clinical problem in sub-Saharan Africa. To date, no post-mortem study has investigated the causes of mortality in these patients. METHODS: HIV-positive adults who died as in-patients at a Johannesburg academic hospital underwent chart-review and ultrasound-guided needle autopsy for histological and microbiological examination of lung, liver, spleen, kidney, bone marrow, lymph node, skin and cerebrospinal fluid. A clinico-pathologic committee considered all available data and adjudicated immediate and contributing causes of death. RESULTS: Thirty-nine adults were enrolled: 14 pre-ART, 15 early-ART (7-90 days), and 10 late-ART (>90 days). Needle sampling yielded adequate specimen in 100% of kidney, skin, heart and cerebrospinal fluid samples, 97% of livers and lungs, 92% of bone marrows, 87% of spleens and 68% of lymph nodes. Mycobacterial infections were implicated in 69% of deaths (26 of 27 of these due to M. tuberculosis), bacterial infections in 33%, fungal infections in 21%, neoplasm in 26%, and non-infectious organ failure in 26%. Immune reconstitution inflammatory syndrome (IRIS) was implicated in 73% of early-ART deaths. Post-mortem investigations revealed previously undiagnosed causes of death in 49% of cases. Multiple pathologies were common with 62% of subjects with mycobacterial infection also having at least one other infectious or neoplastic cause of death. CONCLUSIONS: Needle biopsy was efficient and yielded excellent pathology. The large majority of deaths in all three groups were caused by M. tuberculosis suggesting an urgent need for improved diagnosis and expedited treatment prior to and throughout the course of antiretroviral therapy. Complex, unrecognized co-morbidities pose an additional challenge.

Performance of the Roche LightCycler real-time PCR assay for diagnosing extrapulmonary tuberculosis.

The Roche LightCycler mycobacterium detection molecular assay for Mycobacterium tuberculosis, M. avium, and M. kansasii, was applied to tissue specimens. It performed well on lymph node and cerebrospinal fluid specimens and less well on lung, liver, and bone marrow core biopsy specimens, but used in conjunction with a clinical suspicion of tuberculosis, it could augment patient management.