A low CD4 cell count, weight and haemoglobin can identify which HIV-positive patients are more likely to have undiagnosed TB

Michael Carter
Published: 04 April 2012

Undiagnosed tuberculosis (TB) is common among patients receiving routine HIV care in South Africa, a study published in the online edition of the Journal of Acquired Immune Deficiency Syndromes suggests, reinforcing World Health Organization guidance regarding routine screening of people with HIV for TB.

An international team of investigators found that 12% of patients had confirmed or suspected TB. A low CD4 cell count, even in people taking HIV therapy, was a risk factor, as was low haemoglobin and a low body weight.

"TB symptoms and previously undiagnosed TB were common in this group of ambulatory HIV clinic patients,” write the investigators. “CD4+ T-cell count was the dominant factor associated with having TB, regardless of ART [antiretroviral therapy] status.”

The single biggest worldwide cause of serious illness and death in people with HIV is TB. To reduce the burden of TB in HIV-positive people, the World Health Organization (WHO) endorses a so-called Three I's strategy: intensified TB case finding;isoniazid preventive therapy; and infection control.

However, global implementation of this strategy has been poor in some settings and there are limited data describing the prevalence and risk factors for undiagnosed TB among HIV-positive people receiving routine care.

Therefore, an international team of investigators designed a study involving 422 people who were seen at an HIV primary-care facility in Gauteng Province, South Africa, between 2009 and 2010.

The clinic provided HIV therapy to people with a CD4 cell count below 200 cells/mm3 (the threshold at that time for the initiation of treatment in South Africa).

Patients were screened for TB by checking for symptoms (cough, fever, night sweats and weight loss). Sputum and/or blood culture, chest X-ray and fine-needle aspiration of enlarged lymph nodes were used to confirm suspected cases.

Most of the patients (66%) were female and their median age was 37 years. The overall median CD4 cell count was 215 cells/mm3. A total of 196 patients (47%) were taking HIV therapy and the median duration of treatment was 21 months.

Using symptoms alone, 86% of people were identified as potentially having TB. This prevalence did not differ between the patients taking HIV therapy and those who were not (83 vs 88%).

However, the prevalence of symptoms was significantly higher in people with a CD4 cell count below 100 cells/mm3,compared to people with a CD4 cell count above 200 cells/mm3 (p = 0.027).

Confirmed or suspected TB was diagnosed in a total of 50 patients.

The infection was bacteriologically confirmed in 27 patients; in the other patients it was diagnosed on the basis of chest X-ray or aspiration.

The prevalence of undiagnosed TB was therefore 12%. This was similar in the patients taking HIV therapy and in those who were treatment naive (10 vs 13%). One or more symptom suggestive of TB was reported by 98% of patients with confirmed or suspected TB.

“It is possible that some patients were not appropriately screened for TB prior to ART initiation or during routine visits, and that some TB cases were missed during this screening process,” suggest the authors. “Undiagnosed TB during the first 6 months of ART may also be due to reactivation of latent TB infection or unmasking of TB as part of an immune reconstitution syndrome.”

Patients with a CD4 cell count below 100 cells/mm3 were significantly more likely to have bacteriologically undiagnosed TB than patients with a CD4 cell count above 200 cells/mm3 (OR = 5.05; 95% CI, 1.69-15.12). They also had an increased risk of any form of TB (OR = 2.35; 95% CI, 1.07-5.17).

Individuals with haemoglobin below 10 g/dl had a significantly increased risk of bacteriologically confirmed TB (OR = 2.25; 95% CI, 1.08=4.69).

A low body weight (body mass index [BMI] below 18.5 m2) was also associated with an increased risk of having any form of TB (OR = 2.70; 95% CI, 1.39-5.26).

“In settings where large proportions of patients are symptomatic, TB symptom screening alone may not be useful,” write the authors. “Algorithms which may include BMI, haemoglobin levels and CD4+ T-cell count testing to better target individuals more likely to have undiagnosed TB are needed.”

The authors believe their findings have implications for the Three I’s strategy.

Individuals who did not have symptoms of TB would have been candidates for isoniazid preventive therapy. The results of the study showed that only one patient eligible for this treatment had undiagnosed TB. Although the use of isoniazid preventive therapy by this patient could have resulted in the development of drug resistance, as the authors suggest, it is important to note that WHO guidelines also recommend repeated screening for TB symptoms in people receiving isoniazid preventive therapy.

“Almost half the TB cases in our study were sputum smear or culture positive, indicating that there was a risk of nosocomial [hospital-acquired] transmission of TB in the clinic,” observe the investigators. “We cannot overstate the need to strengthen implementation of administrative and environmental infection control measures.”

They conclude: “Earlier initiation of ART is encouraged to prevent TB and reduce mortality among those who do develop TB."


Kufa T et al. Undiagnosed tuberculosis among HIV clinic attendees: association with antiretroviral therapy and implications for intensified case finding, isoniazid preventive therapy and infection control. J Acquir Immune Defic Syndr, online edition. DOI: 10. 1097/QAI.0b013e318251ae0b, 2012. (Click here for the free abstract.)

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