Intensive screening using sputum cultures found that 32% of South African patients about to start antiretroviral therapy had tuberculosis, investigators report in the on-line edition of AIDS.
This strategy of intensified screening meant the incidence of tuberculosis (TB) during antiretroviral therapy observed in this study was much lower than that identified in other research.
“The data from this study suggest that many incident cases of symptomatic TB presenting during early antiretroviral therapy can be detected as prevalent disease at baseline by routine screening using sensitive diagnostic tests”, write the investigators.
TB is the single biggest cause of illness and death amongst patients with HIV in Africa. There is a high prevalence of the disease in patients starting HIV treatment in the region, and the incidence of TB in the early months of HIV treatment is also high. This is of concern as both prevalent and incident TB are associated with high levels of death, and can also complicate HIV treatment.
To help reduce the burden of TB in people with HIV, the World Health Organization recommends intensive TB case finding. However TB diagnostic methods are relatively insensitive; around one-third of patients may have a normal chest X-ray despite the presence of culture-confirmed TB, and a high proportion of HIV-positive TB cases will be smear-negative, requiring confirmation by sputum culture.
In sick individuals and children however, sputum production for both smear and culture diagnosis may be insufficient. Nevertheless, sputum culture is likely to be the most sensitive method for detecting underlying TB infection.
Investigators in the South African township of Gugulethu, Cape Town, monitored patients about to start HIV treatment. They hypothesised that case finding using two sputum cultures would identify a high level of prevalent TB amongst patients about to start HIV treatment and that many of the new TB cases that emerge in the early months of HIV treatment would be identified as prevalent disease at baseline.
None of the patients had a current TB diagnosis, and all were about to start HIV treatment for the first time.
The patients completed a screening questionnaire, underwent a chest x-ray and provided two sputum samples. If extra-pulmonary TB was suspected, the patients had appropriate investigations to diagnose this.
A total of 241 patients were included in the study. Their median age was 33 and 72% were women. The median CD4 cell count was just 125 cells/mm3, and 54% had symptoms of severe HIV disease. Antiretroviral therapy was started by 200 patients.
Between entry to the study and the completion of one year of HIV treatment, a total of 87 (36%) individuals were diagnosed with TB. The prevalence of the disease at baseline was 32%. The majority of TB cases (89%) detected during the course of the study involved pulmonary TB.
The overwhelming majority of the TB cases (76; 87%) were prevalent cases and were detected by baseline screening.
Patients with TB at baseline had lower CD4 cell counts, higher viral loads, and were more likely to have other symptomatic HIV disease than the individuals who were TB free at this time.
Only a minority of patients diagnosed with TB reported classic symptoms of the disease such as weight loss, fever, and night sweats.
Patients with TB at baseline were significantly less likely than those without the disease to have remained in follow-up or be alive after one year of antiretroviral therapy (59% vs. 73%, p = 0.024).
Of the eight patients who died before starting HIV treatment, six had TB, and 50% of those lost to follow-up were diagnosed with the disease by baseline screening.
Five patients with TB at baseline developed immune reconstitution disease after initiating antiretroviral therapy.
Only eleven cases of TB were diagnosed after patients had started taking HIV treatment. In contrast to earlier research conducted in the same cohort of patients which found an especially high risk of TB during the first few months of HIV treatment, the investigators found that these cases were evenly distributed during the first year of antiretroviral therapy.
The overall TB incidence was 9.2 cases per 100 person years. In the first four months of treatment the incidence was 10.9 cases per 100 person years, and during the following seven months the rate was similar at 8.1 cases per 100 person years.
“Previous data from this cohort have suggest that, under routine programme conditions, approximately 40% of TB cases presenting in the first 4 months of antiretroviral therapy are due to antiretroviral therapy-induced ‘unmasking’ of subclinical active TB that was not diagnosed at baseline. The present data are entirely consistent with this”, comment the investigators.
“There is a strong rationale for routine culture-based screening at the first antiretroviral therapy clinic visit in this setting”, add the investigators. They conclude, “sputum culture-based screening should be used more widely in this clinical setting pending development of simpler and more rapid diagnostic assays.”
For the time being sputum culture remains an expensive and lengthy procedure, and many countries do not have the laboratory capacity to carry out routine sputum culture on all patients. In this study the median time to return a positive result was three weeks, and the investigators note that there is an urgent need for faster sensitive diagnostic methods.
Lawn SD et al. Tuberculosis during the first year of antiretroviral therapy in a South African cohort using an intensive pretreatment screening strategy. AIDS 24, online editiin, DOI: 10.1097/QAD.0b013e3283390dd1, 2010.