Malawi: ART alone isn't enough to stop the TB epidemic among people with HIV

Expanded access to antiretroviral therapy (ART) has been accompanied by big falls in incidence of tuberculosis (TB) in Malawi, according to research published in the Journal of the International AIDS Society. However, rates of TB among people on ART still remained higher than those observed in the general population, underlining the importance of rapid TB diagnosis.

“TB remains a major challenge for HIV-infected people, even in the era of increasing access to ART,” comment the authors. “The high TB incidence and increasing trend in the number of ART patients developing TB after one year on ART provides empirical evidence that ART alone is not enough to prevent TB among HIV-infected patients.”

TB is the leading cause of serious illness and death among people with HIV in the world, accounting for a third of all AIDS-related mortality in 2015. The World Health Organization (WHO) has recommended strengthening HIV/TB service delivery, including improving diagnosis rates, TB infection control, use of isoniazid preventative therapy and prompt initiation of ART.

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.

retrospective study

A type of longitudinal study in which information is collected on what has previously happened to people - for example, by reviewing their medical notes or by interviewing them about past events. 

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.

trend

In everyday language, a general movement upwards or downwards (e.g. every year there are more HIV infections). When discussing statistics, a trend often describes an apparent difference between results that is not statistically significant. 

immune system

The body's mechanisms for fighting infections and eradicating dysfunctional cells.

Use of ART has been associated with a two-thirds reduction in TB risk among people with HIV. However, TB incidence remains high among ART patients in southern Africa, especially during the early months of HIV therapy.

In Malawi, the proportion of people with HIV/TB co-infection treated for TB while on ART increased from 52% in 2011 to 91% in 2017.

Investigators from the Lighthouse Trust were unsure of the reasons for this big increase. They therefore designed a cross-sectional, retrospective study to measure TB incidence over time among HIV-positive people who are taking ART at an integrated public clinic in Lilongwe, Malawi.

Data for the years 2008 to 2017 were obtained from TB registries and ART programmes.

ART eligibility was determined by clinical stage (WHO 3) or according to CD4 cell count. The CD4 cell threshold for starting ART was initially 250 cells/mm3. This increased to 350 cells/mm3 in 2011, to 500 cells/mm3 in 2014 and in 2016, ART was recommended for all people, regardless of CD4 cell count.

During the study period, a total of 22,570 TB cases were reported, the majority (13,808) involving people with HIV. The annual number of TB cases fell both among HIV-negative and HIV-positive people. There were 1455 cases in people with HIV in 2008, falling to 511 cases in 2017.

Reflecting the improved access to ART, the proportion of people with HIV/TB co-infection who were already on ART when they started TB therapy increased from 21% to 81%.

Among people taking ART, TB incidence declined significantly over the time, from 6.0 per 100 person-years in 2008 to 1.1 per 100 person-years in 2013, an 82% reduction. Incidence then remained stable at 1.0 per 100 person-years.

Incidence of TB during the first three months of ART peaked in 2010 at 8.9% but by 2017 had fallen to 3.8%, a reduction of 57%.

Overall TB incidence among ART-treated people was 1.35 per 100 person-years. Incidence was highest during the first three months of ART (6.4 per 100 person-years), partly due to unmasking of subclinical TB because of restoration of the immune system. The longer people took ART, the lower the TB incidence: 1.1 per 100 person-years after two years of HIV therapy and 0.4 per 100 person-years after eight years of ART.

The authors believe their findings show that efforts need to be intensified to increase ART coverage and adherence among people taking HIV therapy. They also assert that the study shows that ART alone is not enough to control TB among people with HIV and there remains a need to invest in TB diagnosis, infection control and preventative therapy.

“TB incidence declined among those on ART by calendar year of ART follow-up [suggesting] the success of both Malawi’s TB control and early ART initiation effort,” conclude the authors. “However, the long-term risk of incident TB among patients on ART and increasing proportion of TB cases attributed by HIV-infected patients receiving ART are concerning.”

They call for the use of sensitive diagnostic technologies including X-rays and GeneXpert (which can rapidly diagnose TB and determine sensitivity to commonly used drugs) at the time of ART initiation.

References

Tweya H et al. The shift in tuberculosis timing among people living with HIV in the course of antiretroviral therapy scale-up in Malawi. Journal of the International AIDS Society 22: e25240, 2019. (Full text freely available).