HIV-positive patients who are co-infected with tuberculosis have poor outcomes in Eastern Europe, a major international study published in the November 27th edition of AIDS shows.
The study involved countries throughout Europe as well as Argentina and showed that patients in Eastern Europe were most likely to be infected with multidrug-resistant tuberculosis (TB), to have disseminated TB, to receive suboptimal TB therapy, and to die.
“This public health disaster should be a call to action against inappropriate medical management of TB, a country-specific problem with global implications”, write the authors of a strongly-worded editorial.
Worldwide, TB is the leading cause of illness and death in people with HIV. Treatment with antiretroviral drugs can dramatically reduce the risk of developing TB, as well as reducing the incidence of the disease.
Although the epidemiology of TB amongst HIV-infected patients in Western Europe is well known, little is known about the situation in Eastern Europe. This is especially concerning as the region has a rapidly expanding HIV epidemic and a high prevalence of multidrug-resistant TB.
Moreover, HIV and TB services in the region are poorly integrated.
In 2006, investigators established a Europe-wide HIV/TB collaboration based upon the EuoSIDA study group which involves 54 countries in the continent plus Argentina.
They wished to compared the clinical characteristics of patients diagnosed with active TB and to analyse regional differences in the treatment offered to individuals and their twelve-month outcomes.
A total of 1075 HIV-positive patients diagnosed with TB between 2004 and 2006 were included in the study. Median CD4 cell count at the time of TB diagnosis was 174 cells/mm3, median body weight was 60 kg, only 18% were taking antiretroviral treatment, and 16% had a viral load below 400 copies/ml.
There were significant regional demographic differences. Patients in Eastern Europe were younger, mostly white, and more likely to be injecting drug users and co-infected with hepatitis C virus. By contrast, those diagnosed with TB in Western Europe were mainly migrants from non-European countries and acquired their HIV infection via heterosexual sex.
Resistance to the key first-line anti-TB drugs isoniazid and rifampicin was significantly more common amongst patients in Eastern Europe than other regions (p < 0.001).
Only 45% of patients in Eastern Europe started a standard first-line TB treatment regimen (containing isoniazid, a rifamycin, pyrazinamide and one other drug). This compared to 87% of patients in Western Europe. The investigators suggest that doctors in Eastern Europe were likely to be avoiding the use of first-line drugs because they lacked information on resistance patterns, and were therefore opting for second-line therapies. However, the study’s authors caution that such a treatment strategy is likely to lead to the emergence of further resistance.
Antiretroviral therapy was initiated by approximately 77% of patients in Western Europe, but only 31% of those in the east.
Outcomes also varied between regions. Overall 59% of patients were defined as successes (cured, or completed treatment). This was highest in Western Europe (85%), and lowest in Eastern Europe (48%, difference, p < 0.0001).
Treatment failed in 4% of patients in the west, but in 13% of those in the east (p < 0.0001).
Twelve months after TB diagnosis, 19% of patients had died. The mortality rate was 5% in Western Europe and 24% in Eastern Europe (p < 0.0001).
Patients in Eastern Europe had a 33% twelve-month probability of death compared to just 8% for those in the west.
A low CD4 cell count (p < 0.0001), treatment with a non-standard first-line TB regimen (p = 0.0024), and disseminated TB (p = 0.0002) were all associated with an increased risk of death.
“Our results emphasise that TB remains a serious comorbidity among HIV-infected patients, especially when combination antiretroviral therapy is not readily available”, comment the investigators.
They add, “the results of this study emphasise that the healthcare needs of HIV/TB patients in Eastern Europe are poorly met”, adding that the situation “deserves further study and urgent public health attention.”
This conclusion was not, however, strong enough for the authors of an accompanying editorial. They write, “the devastating effects of the TB/HIV epidemic must provide the impetus for active enforcement of [treatment] guidelines before first-line TB drugs become obsolete.”
The authors continue, “without adequate treatment and prevention of TB and HIV coinfection, all nations are at risk and some will be left with few to govern.”
The HIV/TB Study Writing Group. Mortality from HIV and TB coinfections is higher in Eastern Europe than in Western Europe and Argentina. AIDS 23: 2485-95, 2009.
Vorkas, CK and van der Host C. HIV and tuberculosis in Russia and Eastern Europe: sounding the alarm. AIDS 23: 2533-34, 2009.