Tuberculosis Incidence Rates during 8 Years of Follow-Up of an Antiretroviral Treatment Cohort in South Africa: Comparison with Rates in the Community

Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
PLoS ONE (Impact Factor: 3.53). 03/2012; 7(3):e34156. DOI: 10.1371/journal.pone.0034156
Source: PubMed

ABSTRACT Although antiretroviral therapy (ART) is known to be associated with time-dependent reductions in tuberculosis (TB) incidence, the long-term impact of ART on incidence remains imprecisely defined due to limited duration of follow-up and incomplete CD4 cell count recovery in existing studies. We determined TB incidence in a South African ART cohort with up to 8 years of follow-up and stratified rates according to CD4 cell count recovery. We compared these rates with those of HIV-uninfected individuals living in the same community.
Prospectively collected clinical data on patients receiving ART in a community-based cohort in Cape Town were analysed. 1544 patients with a median follow-up of 5.0 years (IQR 2.4-5.8) were included in the analysis. 484 episodes of incident TB (73.6% culture-confirmed) were diagnosed in 424 patients during 6506 person-years (PYs) of follow-up. The TB incidence rate during the first year of ART was 12.4 (95% CI 10.8-14.4) cases/100PYs and decreased to 4.92 (95% CI 3.64-8.62) cases/100PYs between 5 and 8 years of ART. During person-time accrued within CD4 cell strata 0-100, 101-200, 201-300, 301-400, 401-500, 501-700 and ≥700 cells/µL, TB incidence rates (95% CI) were 25.5 (21.6-30.3), 11.2 (9.4-13.5), 7.9 (6.4-9.7), 5.0 (3.9-6.6), 5.1 (3.8-6.8), 4.1 (3.1-5.4) and 2.7 (1.7-4.5) cases/100PYs, respectively. Overall, 75% (95% CI 70.9-78.8) of TB episodes were recurrent cases. Updated CD4 cell count and viral load measurements were independently associated with long-term TB risk. TB rates during person-time accrued in the highest CD4 cell count stratum (>700 cells/µL) were 4.4-fold higher that the rate in HIV uninfected individuals living in the same community (2.7 versus 0.62 cases/100PYs; 95%CI 0.58-0.65).
TB rates during long-term ART remained substantially greater than rates in the local HIV uninfected populations regardless of duration of ART or attainment of CD4 cell counts exceeding 700 cells/µL.

Download full-text


Available from: Robin Wood, Jul 07, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mortality rates are high in antiretroviral therapy (ART) programmes in sub-Saharan Africa, especially during the first few months of treatment. Tuberculosis (TB) has been identified as a major underlying cause. Under routine programme conditions, between 5% and 40% of adult patients enrolling in ART services have a baseline diagnosis of TB. There is also a high TB incidence during the first few months of ART (much of which is prevalent disease missed by baseline screening) and long-term rates remain several-fold higher than background. We identify three groups of patients entering ART programmes for which different interventions are required to reduce TB-related deaths. First, diagnostic screening is needed in patients who have undiagnosed active TB so that timely anti-tuberculosis treatment can be started. This may be greatly facilitated by new diagnostic assays such as the Xpert MTB/RIF assay. Second, patients with a diagnosis of active TB need optimised case management, which includes early initiation of ART (with timing now defined by randomised controlled trials), trimethoprim-sulphamethoxazole prophylaxis and treatment of co-morbidity. Third, all remaining patients who are TB-free at enrolment have high ongoing risk of developing TB and require optimised immune recovery (with ART ideally started early in the course of HIV infection), isoniazid preventive therapy and infection control to reduce infection risk. Further specific measures are needed to address multi-drug resistant TB (MDR-TB). Finally, scale-up of all these interventions requires nationally and locally tailored models of care that are patient-centred and provide integrated health care delivery for TB, HIV and other co-morbidities.
    AIDS (London, England) 06/2012; 26(17). DOI:10.1097/QAD.0b013e3283565dd1 · 6.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Every year, HIV-associated tuberculosis (TB) deprives 350,000 mainly young people of productive and healthy lives.People die because TB is not diagnosed and treated in those with known HIV infection and HIV infection is not diagnosed in those with TB. Even in those in whom both HIV and TB are diagnosed and treated, this often happens far too late. These deficiencies can be addressed through the application of new scientific evidence and diagnostic tools. A strategy of starting antiretroviral therapy (ART) early in the course of HIV infection has the potential to considerably reduce both individual and community burden of TB and needs urgent evaluation for efficacy, feasibility and broader social and economic impact. Isoniazid preventive therapy can reduce the risk of TB and, if given strategically in addition to ART, provides synergistic benefit. Intensified TB screening as part of the "Three I's" strategy should be conducted at every clinic, home or community-based attendance using a symptoms-based algorithm, and new diagnostic tools should increasingly be used to confirm or refute TB diagnoses. Until such time when more sensitive and specific TB diagnostic assays are widely available, bolder approaches such as empirical anti-TB treatment need to be considered and evaluated. Patients with suspected or diagnosed TB must be screened for HIV and given cotrimoxazole preventive therapy and ART if HIV-positive. Three large randomized trials provide conclusive evidence that ART initiated within two to four weeks of start of anti-TB treatment saves lives, particularly in those with severe immunosuppression. The key to ensuring that these collaborative activities are delivered is the co-location and integration of TB and HIV services within the health system and the community. Progress towards reducing HIV-associated TB deaths can be achieved through attention to simple and deliverable actions on the ground.
    Journal of the International AIDS Society 07/2012; 15(2):17396. DOI:10.7448/IAS.15.2.17396 · 4.21 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The concentration of CD4 T-lymphocytes (CD4 count), in a person's plasma is widely used to decide when to start HIV-positive people on anti-retroviral therapy (ART) and to predict the impact of ART on the future course of HIV and tuberculosis (TB). However, CD4 cell-counts vary widely within and among populations and depend on many factors besides HIV-infection. The way in which CD4 counts decline over the course of HIV infection is neither well understood nor widely agreed. We review what is known about CD4 counts in relation to HIV and TB and discuss areas in which more research is needed to build a consensus on how to interpret and use CD4 counts in clinical practice and to develop a better understanding of the dynamics and control of HIV and HIV-related TB.