TB Recurrence: Reinfection or Relapse?

Recurrences after successful TB treatment are more common among HIV-positive than HIV-negative patients, and the reasons are different: About half the recurrences in HIV-positive patients represent reinfection rather than reactivation.

Worldwide, tuberculosis (TB) is the most common opportunistic infection (OI) among HIV-positive patients. In regions with a high prevalence of this disease, recurrence is not uncommon among HIV-positive patients, even if they successfully complete TB treatment. Do these recurrences represent relapse or reinfection?

Investigators conducted a population-based study in rural Malawi between 1995 and 2003, when antiretroviral therapy (ART) was not yet available, the prevalence of HIV infection was 14%, and the annual incidence of smear-positive pulmonary TB was 100 cases per 100,000 adults. During the study period, 1287 cases of culture-confirmed TB (mostly pulmonary) occurred: 510 among HIV-positive people, 270 among HIV-negative people, and 507 among people with unknown HIV status. Twenty-one percent of the HIV-positive patients died before TB treatment was completed, versus 4% of the HIV-negative patients.

Among the patients who completed treatment, there were 88 clinically diagnosed recurrences of TB. The recurrence rate was higher among HIV-positive than HIV-negative patients. Fifty-three of the recurrences (31 among people with HIV infection and 22 among those without) were confirmed by culture. DNA fingerprinting on mycobacterial isolates from 39 culture-confirmed episodes revealed that 12 of 23 recurrences among HIV-positive patients represented reinfection, compared with only 1 of 16 among HIV-negative patients. Overall, the rate of reinfection was much higher for HIV-positive than for HIV-negative patients (2.2 vs. 0.4 per 100 person-years); the rate of relapse did not differ between the groups.

Comment

In this high-prevalence setting, reinfection was responsible for about half the culture-confirmed TB recurrences among HIV-positive patients, versus <10% of those among HIV-negative patients. The other important finding is that HIV-positive patients who develop active TB have a high mortality rate despite receiving appropriate TB treatment. Although not entirely surprising, these results underscore the fact that immunosuppression is the major factor underlying morbidity and mortality from TB and that HIV-positive patients with TB coinfection should receive ART to improve their immunologic status. At the end of the day, ART is the best prophylaxis for OIs.

Reviewing Author

Carlos del Rio, MD

Disclosures

Grant/Research SupportNIH/National Institute of Allergy and Infectious Diseases; NIH/National Institute on Drug Abuse

Editorial BoardsJAIDS: Journal of Acquired Immune Deficiency Syndromes; Vaccines

Leadership Positions in Professional SocietiesInternational Antiviral Society–USA (Board of Directors); Infectious Diseases Society of America (Past President)