Browsing by Author "Van Cutsem, Gilles"

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    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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    Correcting for mortality among patients lost to follow up on antiretroviral therapy in South Africa: a cohort analysis
    (Public Library of Science, 2011) Van Cutsem, Gilles; Ford, Nathan; Hildebrand, Katherine; Goemaere, Eric; Mathee, Shaheed; Abrahams, Musaed; Coetzee, David; Boulle, Andrew
    BACKGROUND: Loss to follow-up (LTF) challenges the reporting of antiretroviral treatment (ART) programmes, since it encompasses patients alive but lost to programme and deaths misclassified as LTF. We describe LTF before and after correction for mortality in a primary care ART programme with linkages to the national vital registration system. Methods and FINDINGS: We included 6411 patients enrolled on ART between March 2001 and June 2007. Patients LTF with available civil identification numbers were matched with the national vital registration system to ascertain vital status. Corrected mortality and true LTF were determined by weighting these patients to represent all patients LTF. We used Kaplan-Meier estimates and Cox regression to describe LTF, mortality among those LTF, and true LTF. Of 627 patients LTF, 85 (28.8%) had died within 3 months after their last clinic visits. Respective estimates of LTF before and after correction for mortality were 6.9% (95% confidence interval [CI] 6.2-7.6) and 4.3% (95% CI 3.5-5.3) at one year on ART, and 23.9% (95% CI 21.0-27.2) and 19.7% (95% CI 16.1-23.7) at 5 years. After correction for mortality, the hazard of LTF was reversed from decreasing to increasing with time on ART. Younger age, higher baseline CD4 count, pregnancy and increasing calendar year were associated with higher true LTF. Mortality of patients LTF at 1, 12 and 24 months after their last visits was respectively 23.1%, 30.9% and 43.8%; 78.0% of deaths occurred during the first 3 months after last visit and 45.0% in patients on ART for 0 to 3 months. CONCLUSIONS: Mortality of patients LTF was high and occurred early after last clinic visit, especially in patients recently started on ART. Correction for these misclassified deaths revealed that the risk of true LTF increased over time. Research targeting groups at higher risk of LTF (youth, pregnant women and patients with higher CD4 counts) is needed.
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    Late mortality, loss to follow-up, and associated factors in adults on long term antiretroviral therapy in Khayelitsha
    (2008) Van Cutsem, Gilles; Boulle, Andrew
    The objectives of the study is to estimate baseline characteristics, survival, and factors associated with mortality and losses to follow-up in patients on antiretroviral therapy (ART), and compare the periods before (early) and after (late) 3 months on treatment.
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    Loss from treatment for drug resistant tuberculosis: risk factors and patient outcomes in a community-based program in Khayelitsha, South Africa
    (Public Library of Science, 2015) Moyo, Sizulu; Cox, Helen S; Hughes, Jennifer; Daniels, Johnny; Synman, Leigh; De Azevedo, Virginia; Shroufi, Amir; Cox, Vivian; Van Cutsem, Gilles
    BACKGROUND: A community based drug resistant tuberculosis (DR-TB) program has been incrementally implemented in Khayelitsha, a high HIV and TB burden community in South Africa. We investigated loss from treatment (LFT), and post treatment outcomes of DR-TB patients in this setting. METHODOLOGY: LFT, defined as interruption of treatment for ≥2 consecutive months was assessed among patients initiating DR-TB treatment for the first time between January 2009 and July 2011. Patients were traced through routine data sources to identify those who subsequently restarted treatment and those who died. Additional information on patient status and survival after LTF was obtained from community DR-TB counselors and from the national death registry. Post treatment outcomes were observed until July 2013. RESULTS: Among 452 patients initiating treatment for the first time within the given period, 30% (136) were LFT, with 67% retention at 18 months. Treatment was restarted in 27 (20%) patients, with additional resistance recorded in 2/25 (8%), excluding two with presumed DR-TB. Overall, 34 (25%) patients died, including 11 who restarted treatment. Males and those in the age category 15-25 years had a greater hazard of LFT; HR 1.93 (95% CI 1.35-2.75), and 2.43 (95% CI 1.52-3.88) respectively. Older age (>35 years) was associated with a greater hazard of death; HR 3.74 (1.13- 12.37) post treatment. Overall two-year survival was 62%. It was lower (45%) in older patients, and was 92% among those who received >12 months treatment. CONCLUSION: LFT was high, occurred throughout the treatment period and was particularly high among males and those aged 15-25 years. Overall long term survival was poor. High rates of LFT should however not preclude scale up of community based care given its impact in increasing access to treatment. Further research is needed to support retention of DR-TB patients on treatment, even within community based treatment programs.
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    Monitoring the South African National Antireteoviral Treatment Programme, 2003-2007: The IeDEA Southern Africa Collaboration
    (2009) Cornell, Morna; Technau, Karl; Fairall, Lara; Wood, Robin; Moultrie, Harry; Van Cutsem, Gilles; Giddy, Janet; Mohapi, Lerato; Eley, Brian; MacPhail, Patrick; Prozesky, Hans; Rabie, Helena; Davies, Mary-Ann; Maxwell, Nicola; Boulle, Andrew
    Objectives: To introduce the combined South African cohorts of the International Epidemiologic Databases to Evaluate AIDS-Southern Africa (IeDEA-SA) collaboration as reflecting the South African national antiretroviral treatment (ART) programme; to characterize patients accessing these services; and to describe changes in services and patients 2003-2007. Design & setting Multi-cohort study of 11 ART programmes in Gauteng, Western Cape, Free State and KwaZulu-Natal. Subjects ART-naïve adults and children (<16 years old) who initiated ART with ≥3 antiretroviral drugs before 2008. Results: Most sites were offering free treatment to adults and children in the public sector, ranging from 264 to 17,835 patients per site. Among 45,383 adults and 6,198 children combined, median (IQR) range was 35.0 years (29.8-41.4) and 42.5 months (14.7-82.5) respectively. Of adults, 68% were female. Median CD4 cell count was 102 cells/µL (44-164) and was lower among males than females (86, 34-150 vs 110, 50-169, p<0.001). Median CD4% among children was 12% (7-17.7). Between 2003 and 2007, enrolment increased 11-fold in adults and 3-fold in children. Median CD4 count at enrolment increased for all adults (67-111 cells/µL, p<0.001) and for those in Stage IV (39-89 cells/µL, p<0.001). Among children <5 years, baseline CD4% increased over time (11.5%-16.0%, p<0.001). Conclusions: IeDEA-SA provides a unique opportunity to report on the national ART programme. The study describes dramatically increasing enrolment. Late presentation, especially of men and children, remains a concern. Investment in sentinel sites ensures good individual-level data while freeing most sites to continue with simplified reporting.
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    Nevirapine-associated early hepatotoxicity: incidence, risk factors, and associated mortality in a primary care ART programme in South Africa
    (Public Library of Science, 2010) Chu, Kathryn M; Boulle, Andrew M; Ford, Nathan; Goemaere, Eric; Asselman, Valerie; Van Cutsem, Gilles
    BACKGROUND: The majority of antiretroviral treatment programmes in sub-Saharan Africa are scaling up antiretroviral treatment using a fixed dose first-line antiretroviral regimen containing stavudine, lamivudine, and nevirapine. One of the primary concerns with the use of this regimen is nevirapine-associated hepatotoxicity. METHODOLOGY/PRINCIPAL FINDINGS: Study participants were 1809 HIV-infected, antiretroviral naïve adults initiating nevirapine-based antiretroviral therapy between November 2002 and December 2006. The primary outcome was early hepatotoxicity. Secondary outcomes were associations with hepatotoxicity and mortality at six months. The cumulative proportion of early hepatotoxicity ranged from 1.0-2.0% giving an incidence-rate at 102 days of 3.6-7.6 per 100 person-years. Median time to hepatotoxicity was 32 (IQR 28-58) days. At 12 weeks, only 8% of patients had alanine aminotransferase monitoring at all the time-points recommended by national guidelines. No association was found between age, gender, baseline CD4 count, concurrent tuberculosis infection, prior participation in a prevention of mother-to-child-transmission program, or baseline weight and early hepatotoxicity. There was no association between early hepatotoxicity and mortality. CONCLUSIONS: The cumulative proportion of early hepatotoxicity in nevirapine based antiretroviral therapy was low in this resource-constrained setting. Hepatotoxicity was not associated with mortality. Frequent routine monitoring of alanine aminotransferase proved difficult to implement in this public sector primary care programme. Focused monitoring in the first month may be a more cost-effective and pragmatic option in settings with limited resources. Correlation with clinical signs and symptoms may allow future alanine aminotransferase testing to be dictated by clinical criteria.
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    Progress towards the UNAIDS 90–90-90 goals by age and gender in a rural area of KwaZulu-Natal, South Africa: a household-based community cross-sectional survey
    (BioMed Central, 2018-03-02) Huerga, Helena; Van Cutsem, Gilles; Ben Farhat, Jihane; Puren, Adrian; Bouhenia, Malika; Wiesner, Lubbe; Dlamini, Linda; Maman, David; Ellman, Tom; Etard, Jean-François
    Abstract Background The Joint United Nations Programme on HIV/AIDS (UNAIDS) has developed an ambitious strategy to end the AIDS epidemic. After eight years of antiretroviral therapy (ART) program we assessed progress towards the UNAIDS 90–90-90 targets in Mbongolwane and Eshowe, KwaZulu-Natal, South Africa. Methods We conducted a cross-sectional household-based community survey using a two-stage stratified cluster probability sampling strategy. Persons aged 15–59 years were eligible. We used face-to-face interviewer-administered questionnaires to collect information on history of HIV testing and care. Rapid HIV testing was performed on site and venous blood specimens collected from HIV-positive participants for antiretroviral drug presence test, CD4 count and viral load. At the time of the survey the CD4 threshold for ART initiation was 350 cells/μL. We calculated progression towards the 90–90-90 UNAIDS targets by estimating three proportions: HIV positive individuals who knew their status (first 90), those diagnosed who were on ART (second 90), and those on ART who were virally suppressed (third 90). Results We included 5649/6688 (84.5%) individuals. Median age was 26 years (IQR: 19–40), 62.3% were women. HIV prevalence was 25.2% (95% CI: 23.6–26.9): 30.9% (95% CI: 29.0–32.9) in women; 15.9% (95% CI: 14.0–18.0) in men. Overall progress towards the 90–90-90 targets was as follows: 76.4% (95% CI: 74.1–78.6) knew their status, 69.9% (95% CI: 67.0–72.7) of those who knew their status were on ART and 93.1% (95% CI: 91.0–94.8) of those on ART were virally suppressed. By sex, progress towards the 90–90-90 targets was: 79%–71%–93% among women; and 68%–68%–92% among men (p-values of women and men comparisons were < 0.001, 0.443 and 0.584 respectively). By age, progress was: 83%–75%–95% among individuals aged 30–59 years and 64%–58%–89% among those aged 15–29 years (p-values of age groups comparisons were < 0.001, < 0.001 and 0.011 respectively). Conclusions In this context of high HIV prevalence, significant progress has been achieved with regards to reaching the UNAIDS 90–90-90 targets. The third 90, viral suppression in people on ART, was achieved among women and men. However, gaps persist in HIV diagnosis and ART coverage particularly in men and individuals younger than 30 years. Achieving 90–90-90 is feasible but requires additional investment to reach youth and men.