Preventive TB treatment warranted for some HIV patients in the UK

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HIV-positive patients with latent tuberculosis (TB) should be provided with preventive TB therapy, UK investigators recommend in an article published in the online edition of AIDS. The investigators found that TB was an important cause of illness in a large cohort of UK HIV patients, and was most frequently diagnosed in patients with a low CD4 cell count and those of African origin.

Moreover, African patients continued to have a high incidence of TB even after starting HIV treatment.

“The analysis highlights the substantial and increasing importance of tuberculosis as a cause of HIV-related disease in the UK, particularly among black African individuals”, write the investigators.

Glossary

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

latent TB

A form of TB that is not active. Persons with latent TB are infected with M. tuberculosis but do not have any symptoms and they cannot spread TB infection to others. Only specific tests will tell if anyone has latent TB. Treatment for latent TB is recommended in people living with HIV. 

acute infection

The very first few weeks of infection, until the body has created antibodies against the infection. During acute HIV infection, HIV is highly infectious because the virus is multiplying at a very rapid rate. The symptoms of acute HIV infection can include fever, rash, chills, headache, fatigue, nausea, diarrhoea, sore throat, night sweats, appetite loss, mouth ulcers, swollen lymph nodes, muscle and joint aches – all of them symptoms of an acute inflammation (immune reaction).

active TB

Active disease caused by Mycobacterium tuberculosis, as evidenced by a confirmatory culture, or, in the absence of culture, suggestive clinical symptoms.

infection control

Infection prevention and control (IPC) aims to prevent or stop the spread of infections in healthcare settings. Standard precautions include hand hygiene, using personal protective equipment, safe handling and disposal of sharp objects (relevant for HIV and other blood-borne viruses), safe handling and disposal of waste, and spillage management.

TB is the most important cause of HIV-related illness and death around the world, especially in Africa. Individuals from Africa constitute an increasing proportion of patients with HIV in the UK, and there has been a substantial increase in TB diagnoses in the UK in recent years.

Preventive therapy can reduce the incidence of TB in HIV-positive patients and is recommended by the World Health Organization. However, British HIV guidelines do not recommend routine screening for active or latent TB, nor do they make any clear recommendations about the use of preventive therapy.

Investigators from the UK Collaborative HIV Cohort (UK CHIC) conducted an observation study involving patients attending UK HIV clinics between 1996 and 2006 to establish the incidence of TB before and after starting HIV treatment and the risk factors for the development of active TB once HIV therapy has been started.

A total of 27,868 patients were included in the cohort and 741 (3%) experienced one or more episode of TB. Almost 50% of these episodes occurred in the first three months of attendance at an HIV clinic.

The investigators then restricted their analysis to 22,833 patients with more than three months of follow-up with CD4 cell count measurements.

Just under a quarter (23%) of these patients were black African, and on entry to the cohort, these patients had significantly lower CD4 cell counts than either white patients, or patients of other ethnicities (265 vs 356 vs 330 cells/mm3, p 3 after HIV treatment was started than patients of white or other ethnicities (22% vs 16% vs 16%).

A total of 370 patients experienced one or more episode of TB three or more months after entry to the cohort, providing an incidence of 3.28 per 100 person years. The incidence rate was much higher in African patients than those of white ethnicity (8.45 vs 3.75 per 100 person years).

Amongst patients not taking HIV therapy (15,607 individuals, contributing 38,000 person years of follow-up), the incidence of TB was significantly higher amongst individuals of African origin than those who were white or of other ethnicities 9.9 vs 2.5 vs 4.4 per 100 person years.

In all racial groups TB incidence was substantially higher amongst patients with lower CD4 cell counts than amongst those with a CD4 cell count above 500 cells/mm3.

HIV treatment was provided to 7181 patients who contributed 74,500 person years of follow-up. The overall tuberculosis incidence in these patients was 3 per 100 person years.

Incidence of the disease was highest in the first three months after starting HIV therapy (13.3 per 100 person years), but had fallen to 1.8 per 100 person years after two years of antiretroviral therapy. However, the incidence of TB remained high in patients of African origin even after two years of antiretroviral treatment (5.3 per 100 person years).

The strongest risk factor for the development of TB after the initiation of antiretroviral therapy was a low CD4 cell count, the risk being especially high for patients with a CD4 cell count below 50 cells/mm3 compared to individuals with at least 200 cells/mm3 (adjusted risk ratio [aRR] =10.65; 95% CI, 6.11-18.57 vs. aRR = 1.77, 95% CI, 1.09-3.12).

Patients of African origin had a higher risk of TB compared to white patients (aRR = 2.93; 95% CI, 1.89-4.54).

“We found a very strong association between CD4 cell count and the risk of incident tuberculosis after starting combination antiretroviral therapy”, comment the investigators.

Noting the high incidence of TB amongst African patients, the investigators suggest that this “is most likely attributable to a combination of a higher risk of previous tuberculosis exposure and thus tuberculosis infection, compounded by lower CD4 cell counts at study entry and after the start of combination antiretroviral therapy.” The authors also emphasise that the risk of TB remained high for African patients, even after HIV treatment was started.

On the basis of these findings the investigators recommend that “in addition to timely initiation of combination antiretroviral therapy, HIV clinics should screen new patients for acute tuberculosis, implement infection control measures, and offer tuberculosis preventative therapy, particularly to migrants from settings of high tuberculosis prevalence…individuals with evidence suggesting latent tuberculosis infection should be targeted for preventative therapy”.

References

United Kingdom Collaborative HIV Cohort Study Group. Tuberculosis among people with HIV infection in the United Kingdom: opportunities for prevention? AIDS 23 (online edition), 2009.