Browsing by Subject "AIDS-Related Opportunistic Infections"

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    Open Access
    AIDS-associated Kaposi's sarcoma is linked to advanced disease and high mortality in a primary care HIV programme in South Africa
    (BioMed Central Ltd., 2010) Chu, Kathryn; Mahlangeni, Gcina; Swannet, Sarah; Ford, Nathan; Boulle, Andrew; Van Cutsem, Gilles
    BACKGROUND: AIDS-associated Kaposi's sarcoma is an important, life-threatening opportunistic infection among people living with HIV/AIDS in resource-limited settings. In western countries, the introduction of combination antiretroviral therapy (cART) and new chemotherapeutic agents has resulted in decreased incidence and improved prognosis of AIDS-associated Kaposi's sarcoma. In African cohorts, however, mortality remains high. In this study, we describe disease characteristics and risk factors for mortality in a public sector HIV programme in South Africa. METHODS: We analysed data from an observational cohort study of HIV-infected adults with AIDS-associated Kaposi's sarcoma, enrolled between May 2001 and January 2007 in three primary care clinics. Paper records from primary care and tertiary hospital oncology clinics were reviewed to determine the site of Kaposi's sarcoma lesions, immune reconstitution inflammatory syndrome stage, and treatment. Baseline characteristics, cART use and survival outcomes were extracted from an electronic database maintained for routine monitoring and evaluation. Cox regression was used to model associations with mortality. RESULTS: Of 6292 patients, 215 (3.4%) had AIDS-associated Kaposi's sarcoma. Lesions were most commonly oral (65%) and on the lower extremities (56%). One quarter of patients did not receive cART. The mortality and lost-to-follow-up rates were, respectively, 25 (95% CI 19-32) and eight (95% CI 5-13) per 100 person years for patients who received cART, and 70 (95% CI 42-117) and 119 (80-176) per 100 person years for patients who did not receive cART. Advanced T stage (adjusted HR, AHR = 5.3, p < 0.001), advanced S stage (AHR = 5.1, p = 0.008), and absence of chemotherapy (AHR = 2.4, p = 0.012) were associated with mortality.Patients with AIDS-associated Kaposi's sarcoma presented with advanced disease and high rates of mortality and loss to follow up. Risk factors for mortality included advanced Kaposi's sarcoma disease and lack of chemotherapy use. Contributing factors to the high mortality for patients with AIDS-associated Kaposi's sarcoma likely included late diagnosis of HIV disease, late accessibility to cART, and sub-optimal treatment of advanced Kaposi's sarcoma. CONCLUSIONS: These findings confirm the importance of early access to both cART and chemotherapy for patients with AIDS-associated Kaposi's sarcoma. Early diagnosis and improved treatment protocols in resource-poor settings are essential.
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    Are the effects of isoniaid preventive therapy and highly active antiretroviral therapy additive in preventing HIV-associated tuberculosis
    (2009) Wood, Robin; Lawn, Stephen D; Bekker, Linda-Gail
    Golub et al. [1] recently reported a retrospective analysis of rates of incident tuberculosis (TB) in a large observational cohort of 2778 patients accessing HIV care in rural and urban South Africa. The TB incidence rate was highest [7.1/100 person-years; 95% confidence interval (CI)¼ 6.2–8.2] during the period of care when patients did not receive isoniazid preventive therapy (IPT) or highly active antiretroviral therapy (HAART). The rates were lower during person-time that accrued throughout follow-up after initiation of IPT (5.2/100 person-years; 95% CI¼ 3.4–7.8) and throughout follow-up on HAART alone (4.6/100 person-years, 95% CI¼ 3.4– 6.2). The rate was lower still (1.1/100 person-years 95% CI¼ 0.2–7.6) during person-time accrued during sequential IPT and HAART (IPTþ HAART). The authors concluded that TB risk was significantly reduced by IPT in HAART-treated adults. It was further concluded that ‘the dramatic reduction in TB risk’ demonstrated in this study together with supportive data from a similarly analysed study from Brazil [2] indicates that widespread use 1444 AIDS 2009, Vol 23 No 11 Fig. 1. T2-weighted flair image demonstrating enhancing lesion in the right precentral gyrus. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. of IPT should be implemented in conjunction with the roll-out of HAART.
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    Open Access
    Are the effects of isoniaid preventive therapy and highly active antiretroviral therapy additive in preventing HIV-associated tuberculosis
    (2009) Wood, Robin; Lawn, Stephen D; Bekker, Linda-Gail
    Golub et al. [1] recently reported a retrospective analysis of rates of incident tuberculosis (TB) in a large observational cohort of 2778 patients accessing HIV care in rural and urban South Africa. The TB incidence rate was highest [7.1/100 person-years; 95% confidence interval (CI)¼ 6.2–8.2] during the period of care when patients did not receive isoniazid preventive therapy (IPT) or highly active antiretroviral therapy (HAART). The rates were lower during person-time that accrued throughout follow-up after initiation of IPT (5.2/100 person-years; 95% CI¼ 3.4–7.8) and throughout follow-up on HAART alone (4.6/100 person-years, 95% CI¼ 3.4– 6.2). The rate was lower still (1.1/100 person-years 95% CI¼ 0.2–7.6) during person-time accrued during sequential IPT and HAART (IPTþ HAART). The authors concluded that TB risk was significantly reduced by IPT in HAART-treated adults. It was further concluded that 'the dramatic reduction in TB risk' demonstrated in this study together with supportive data from a similarly analysed study from Brazil [2] indicates that widespread use 1444 AIDS 2009, Vol 23 No 11 Fig. 1. T2-weighted flair image demonstrating enhancing lesion in the right precentral gyrus. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. of IPT should be implemented in conjunction with the roll-out of HAART.
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    Early morning urine collection to improve urinary lateral flow LAM assay sensitivity in hospitalised patients with HIV-TB co-infection
    (2017) Gina, Phindile; Randall, Philippa J; Muchinga, Tapuwa E; Pooran, Anil; Meldau, Richard; Peter, Jonny G; Sabur, Natasha F
    BACKGROUND: Urine LAM testing has been approved by the WHO for use in hospitalised patients with advanced immunosuppression. However, sensitivity remains suboptimal. We therefore examined the incremental diagnostic sensitivity of early morning urine (EMU) versus random urine sampling using the Determine® lateral flow lipoarabinomannan assay (LF-LAM) in HIV-TB co-infected patients. METHODS: Consenting HIV-infected inpatients, screened as part of a larger prospective randomized controlled trial, that were treated for TB, and could donate matched random and EMU samples were included. Thus paired sample were collected from the same patient, LF-LAM was graded using the pre-January 2014, with grade 1 and 2 manufacturer-designated cut-points (the latter designated grade 1 after January 2014). Single sputum Xpert-MTB/RIF and/or TB culture positivity served as the reference standard (definite TB). Those treated for TB but not meeting this standard were designated probable TB. RESULTS: 123 HIV-infected patients commenced anti-TB treatment and provided matched random and EMU samples. 33% (41/123) and 67% (82/123) had definite and probable TB, respectively. Amongst those with definite TB LF-LAM sensitivity (95%CI), using the grade 2 cut-point, increased from 12% (5-24; 5/43) to 39% (26-54; 16/41) with random versus EMU, respectively (p = 0.005). Similarly, amongst probable TB, LF-LAM sensitivity increased from 10% (5-17; 8/83) to 24% (16-34; 20/82) (p = 0.001). LF-LAM specificity was not determined. CONCLUSION: This proof of concept study indicates that EMU could improve the sensitivity of LF-LAM in hospitalised TB-HIV co-infected patients. These data have implications for clinical practice.
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    Prolonged deferral of antiretroviral therapy in the SAPIT trial: Did we need a clinical trial to tell us that this would increase mortality?
    (2010) Boulle, Andrew; Clayden, Polly; Cohen, Karen; Cohen, Ted; Conradie, Francesca; Dong, Christa; Geffen, Nathan; Grimwood, Ashraf; Hurtado, Rocio; Kenyon, Christopher; Lawn, Stephen; Maartens, Gary; Meintjes, Graeme; Mendelson, Marc; Murray, Megan; Rangaka, Molebogeng; Sanne, Ian; Spencer, David; Taljaard, Jantjie; Variava, Ebrahim; Venter, W D Francois; Wilson, Douglas
    Tuberculosis is the major cause of morbidity and mortality in HIVinfected patients in sub-Saharan Africa. HIV infection is often first diagnosed following a diagnosis of tuberculosis, with many patients needing antiretroviral therapy (ART). Starting ART in HIV-infected patients with tuberculosis (TB) may be associated with complications, including side-effects from co-administration of multiple drugs with many overlapping toxicities, reductions in concentrations of certain antiretroviral drugs following the induction of metabolising enzymes and drug transporters by rifampicin, and paradoxical deterioration due to the immune reconstitution inflammatory syndrome (IRIS). Furthermore, the high pill burden of co-treatment could reduce adherence, resulting in poor treatment outcomes for both diseases. These potential harms must be weighed against the high mortality rates in patients with HIV-associated tuberculosis who do not receive ART, especially those with low CD4 counts. The optimal time to initiate ART in patients with tuberculosis is an important research question, and randomised controlled trials are addressing this issue.
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    Rapid urine-based screening for tuberculosis to reduce AIDS-related mortality in hospitalized patients in Africa (the STAMP trial): study protocol for a randomised controlled trial
    (2016) Gupta-Wright, Ankur; Fielding, Katherine L; van Oosterhout, Joep J; Wilson, Douglas K; Corbett, Elizabeth L; Flach, Clare; Reddy, Krishna P; Walensky, Rochelle P; Peters, Jurgens A; Alufandika-Moyo, Melanie; Lawn, Stephen D
    Abstract Background HIV-associated tuberculosis (TB) co-infection remains an enormous burden to international public health. Post-mortem studies have highlighted the high proportion of HIV-positive adults admitted to hospital with TB. Determine TB-LAM and Xpert MTB/RIF assays can substantially increase diagnostic yield of TB within one day of hospital admission. However, it remains unclear if this approach can impact clinical outcomes. The STAMP trial aims to test the hypothesis that the implementation a urine-based screening strategy for TB can reduce all cause-mortality among HIV-positive patients admitted to hospital when compared to current, sputum-based screening. Methods The trial is a pragmatic, individually randomised, multi-country (Malawi and South Africa) clinical trial with two study arms (1:1 recruitment). Unselected HIV-positive patients admitted to medical wards, irrespective of presentation, meeting the inclusion criteria and giving consent will be randomized to screening for TB using either: (i) ‘standard of care’- testing of sputum using the Xpert MTB/RIF assay (Xpert) or (ii) ‘intervention’- testing of sputum using Xpert and testing of urine using (a) Determine TB-LAM lateral-flow assay and (b) Xpert following concentration of urine by centrifugation. Patients will be excluded if they have received TB treatment in the previous 12 months, if they have received isoniazid preventive therapy in the last 6 months, if they are aged <18 years or they live outside the pre-specified geographical area. Results will be provided to the responsible medical team as soon as available to inform decisions regarding TB treatment. Both the study and routine medical team will be masked to study arm allocation. 1300 patients will be enrolled per arm (equal numbers at the two trial sites). The primary endpoint is all-cause mortality at 56 days. An economic analysis will be conducted to project long-term outcomes for shorter-term trial data, including cost-effectiveness. Discussion This pragmatic trial assesses an intervention to reduce the high mortality caused by HIV-associated TB, which could feasibly be scaled up in high-burden settings if shown to be efficacious and cost-effective. We discuss the challenges of designing a trial to assess the impact on mortality of laboratory-based TB screening interventions given frequent initiation of empirical treatment and a failure of several previous clinical trials to demonstrate an impact on clinical outcomes. We also elaborate on the practical and ethical issues of ‘testing a test’ in general. Trial registration ISRCTN Registry (ISRCTN71603869) prospectively registered 08 May 2015; the South African National Controlled Trials Registry (DOH-27-1015-5185) prospectively registered October 2015.