{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:31:33Z","timestamp":1790958693057,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,6,23]],"date-time":"2017-06-23T00:00:00Z","timestamp":1498176000000},"content-version":"vor","delay-in-days":173,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["324730_149792"],"award-info":[{"award-number":["324730_149792"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of the International AIDS Society"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Introduction<\/jats:bold>: Chronic immune activation due to ongoing HIV replication may lead to impaired immune responses against opportunistic infections such as tuberculosis (TB). We studied the role of HIV replication as a risk factor for incident TB after starting antiretroviral therapy (ART).<\/jats:p><jats:p><jats:bold>Methods<\/jats:bold>: We included all HIV\u2010positive adult patients (\u226516\u00a0years) in care between 2000 and 2014 at three ART programmes in South Africa. Patients with previous TB were excluded. Missing CD4 cell counts and HIV\u2010RNA viral loads at ART start (baseline) and during follow\u2010up were imputed. We used parametric survival models to assess TB incidence (pulmonary and extrapulmonary) by CD4 cell and HIV\u2010RNA levels, and estimated the rate ratios for TB by including age, sex, baseline viral loads, CD4 cell counts, and WHO clinical stage in the model. We also used Poisson general additive regression models with time\u2010updated CD4 and HIV\u2010RNA values, adjusting for age and sex.<\/jats:p><jats:p><jats:bold>Results<\/jats:bold>: We included 44,260 patients with a median follow\u2010up time of 2.7\u00a0years (interquartile range [IQR] 1.0\u20135.0); 3,819 incident TB cases were recorded (8.6%). At baseline, the median age was 34\u00a0years (IQR 28\u201341); 30,675 patients (69.3%) were female. The median CD4 cell count was 156 cells\/\u00b5L (IQR 79\u2013229) and the median HIV\u2010RNA viral load 58,000 copies\/mL (IQR 6,000\u2013240,000). Overall TB incidence was 26.2\/1,000 person\u2010years (95% confidence interval [CI] 25.3\u201327.0). Compared to the lowest viral load category (0\u2013999 copies\/mL), the adjusted rate ratio for TB was 1.41 (95% CI 1.15\u20131.75, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001) in the highest group (&gt;10,000 copies\/mL). Time\u2010updated analyses for CD4\/HIV\u2010RNA confirmed the association of viral load with the risk for TB.<\/jats:p><jats:p><jats:bold>Conclusions<\/jats:bold>: Our results indicate that ongoing HIV replication is an important risk factor for TB, regardless of CD4 cell counts, and underline the importance of early ART start and retention on ART.<\/jats:p>","DOI":"10.7448\/ias.20.1.21327","type":"journal-article","created":{"date-parts":[[2017,6,22]],"date-time":"2017-06-22T08:59:03Z","timestamp":1498121943000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["HIV viral load as an independent risk factor for tuberculosis in South Africa: collaborative analysis of cohort studies"],"prefix":"10.1002","volume":"20","author":[{"given":"Lukas","family":"Fenner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Atkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Boulle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P.","family":"Fox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Prozesky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Z\u00fcrcher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Ballif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hansjakob","family":"Furrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Zwahlen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary\u2010Ann","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Egger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the International Epidemiology Database to Evaluate AIDS in Southern Africa (IeDEA\u2010SA)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,6,23]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"World Health Organization.Global tuberculosis report 2014.World Health Organization Document.2014;WHO\/HTM\/TB\/2014.08:1\u2013149."},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-124-7-199604010-00003"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1086\/339540"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/367655"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)01122-8"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)68337-2"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2012-201740"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200109280-00012"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00042560-200206010-00003"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1086\/655761"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-011110-130254"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyr080"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0077697"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/tmi.12026"},{"key":"e_1_2_11_16_1","unstructured":"HonakerJ KingG BlackwellM. 2012. 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