HIV viral load as an independent risk factor for tuberculosis in South Africa: collaborative analysis of cohort studies.

Fenner, Lukas; Atkinson, Andrew; Boulle, Andrew; Fox, Matthew P; Prozesky, Hans; Zürcher, Kathrin; Ballif, Marie; Furrer, Hansjakob; Zwahlen, Marcel; Davies, Mary-Ann; Egger, Matthias; eDEA-SA, Int. Epidemiology Database to Evaluate AIDS in Southern Africa (2017). HIV viral load as an independent risk factor for tuberculosis in South Africa: collaborative analysis of cohort studies. Journal of the International AIDS Society, 20(1), p. 21327. BioMed Central 10.7448/IAS.20.1.21327

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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).


We included all HIV-positive adult patients (≥16 years) 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-RNA viral loads at ART start (baseline) and during follow-up were imputed. We used parametric survival models to assess TB incidence (pulmonary and extrapulmonary) by CD4 cell and HIV-RNA 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-updated CD4 and HIV-RNA values, adjusting for age and sex.


We included 44,260 patients with a median follow-up time of 2.7 years (interquartile range [IQR] 1.0-5.0); 3,819 incident TB cases were recorded (8.6%). At baseline, the median age was 34 years (IQR 28-41); 30,675 patients (69.3%) were female. The median CD4 cell count was 156 cells/µL (IQR 79-229) and the median HIV-RNA viral load 58,000 copies/mL (IQR 6,000-240,000). Overall TB incidence was 26.2/1,000 person-years (95% confidence interval [CI] 25.3-27.0). Compared to the lowest viral load category (0-999 copies/mL), the adjusted rate ratio for TB was 1.41 (95% CI 1.15-1.75, p < 0.001) in the highest group (>10,000 copies/mL). Time-updated analyses for CD4/HIV-RNA confirmed the association of viral load with the risk for TB.


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.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine (ISPM)
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Infectiology

UniBE Contributor:

Fenner, Lukas, Atkinson, Andrew David, Zürcher, Kathrin, Ballif, Marie, Furrer, Hansjakob, Zwahlen, Marcel, Egger, Matthias


600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services




BioMed Central




Tanya Karrer

Date Deposited:

08 Aug 2017 16:39

Last Modified:

05 Dec 2022 15:06

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

CD4 cell count HIV antiretroviral treatment incidence opportunistic infection prediction time-updated tuberculosis viral load




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