HIV infection not found to be associated with drug-resistant TB in Khayelitsha South Africa

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An extremely high prevalence of 72 per 100 000 per year of rifampicin-resistant tuberculosis (TB) has been found in a cross sectional study of individuals with suspected TB conducted in Khayelitsha township, situated 40 km outside of Cape Town.

However, HIV infection was not found to be significantly associated with drug-resistant TB (DR TB) in this study, but individuals who had previously received TB treatment and women appeared to be at particular risk for drug-resistant TB in Khayelitsha, Dr Helen Cox of Médècins sans Frontiéres told the Fifth International AIDS Society Conference in Cape Town.

Khayelitsha is served by one of Médècins sans Frontiéres’ oldest antiretroviral programmes and has a high HIV prevalence and a very high incidence of TB.

Glossary

culture

In a bacteria culture test, a sample of urine, blood, sputum or another substance is taken from the patient. The cells are put in a specific environment in a laboratory to encourage cell growth and to allow the specific type of bacteria to be identified. Culture can be used to identify the TB bacteria, but is a more complex, slow and expensive method than others.

smear

A specimen of tissue or other material taken from part of the body and smeared onto a microscope slide for examination. A Pap smear is a specimen of material scraped from the cervix (neck of the uterus) examined for precancerous changes.

sputum

Material coughed up from the lungs, which can be examined to help with diagnosis and management of respiratory diseases.

multidrug-resistant tuberculosis (MDR-TB)

A specific form of drug-resistant TB, due to bacilli resistant to at least isoniazid and rifampicin, the two most powerful anti-TB drugs. MDR-TB usually occurs when treatment is interrupted, thus allowing organisms in which mutations for drug resistance have occurred to proliferate.

cross-sectional study

A ‘snapshot’ study in which information is collected on people at one point in time. See also ‘longitudinal’.

The study aimed to determine the prevalence of drug-resistant TB and the association with HIV infection among TB cases diagnosed, as no clear evidence exists as to whether HIV infection contributes to the emergence of drug-resistant TB over and above the impact it has on individual risk of developing drug-susceptible TB.

A cross-sectional study was conducted where sputum samples were collected from 1846 eligible individuals suspected for pulmonary TB in two large primary care clinics in Khayelitsha, which collectively account for 50% of the TB burden in Khayelitsha.

Sputum smear microscopy was conducted on two sputum specimens and the MGIT culture test was conducted on a third smear specimen. Resistance to rifampicin and isoniazid was determined on all positive cultures using the Hain Geno Type MRBDR Plus rapid line probe assay.

Five hundred and forty-four of the 1846 patients (29.5%) suspected of having TB who were included in the study were confirmed as culture-positive for TB.

Of those diagnosed with culture positive TB, 53.9% were coinfected with HIV and 51% had smear-positive TB.

Resistance to rifampicin was found in 43 of the 544 (7.9%) culture-positive TB cases. Isoniazid resistance results were not used from the rapid line probe assay.

In 2008, there were 5,791 TB cases registered in Khayelitsha. Applying the survey estimates of rifampicin resistance would result in an estimated 360 rifampicin-resistant TB cases for 2008 which equates to an estimated incidence for drug-resistant TB of 72 per 100,000 per year.

Resistance to rifampicin was found in 10.8% of patients who had previously received TB therapy compared to 4.5% of individuals being treated with anti-TB drugs for the first time. This difference was significant (p = 0.003).

Results showed that previous treatment for TB (odds ratio [OR] = 3.2; 95% CI, 1.4-7.1) and female sex (OR = 2.9; 95% CI, 1.3 – 6.2) were the only factors associated with a diagnosis of rifampicin-resistant TB. Whether this reflects an inherently greater susceptibility for women or a greater likelihood of exposure and thereby transmission risk in certain settings is not clear. Dr Helen Cox suggested that a possible reason for women being at greater risk could be due to women predominantly being the caregivers of those ill with TB or due to nosocomial transmission as women spend more time in health care facilities than men. Further investigation is needed into this.

There was no association between rifampicin-resistant TB diagnosis and HIV. Further analysis by the investigators also failed to find any significant interactions between HIV and either previous TB therapy or female sex.

Although patients with HIV also had a higher prevalence of resistance to rifampicin than HIV-negative patients (9.3% vs. 5.5%), the difference did not achieve significance.

Among HIV-positive rifampicin-resistant TB cases, those already on antiretrovirals (ART) at the time of diagnosis are significantly more likely to have rifampicin-resistant TB (OR=3.7, 95%CI 1.4 – 9,8).

This again was suggested to be possibly due to nosocomial transmission in health care facilities when patients access ART, although more research is needed in this area.

Although an association has been shown in some parts of Eastern Europe and in MDR-TB outbreaks in institutionalised settings, a significant association between MDR TB and HIV infection could not be found in a systematic review containing 32 studies.

While studies from low TB incidence settings such as the United States of America suggest that there is an association between HIV infection and MDR TB, no association was seen among the studies included from Africa.

Further information

A powerpoint presentation by Helen Cox and a webcast of the conference session in which it was presented are available on the IAS 2009 website.

References

Cox H et al. Prevalence of drug resistant tuberculosis and association with HIV in Khayelitsha, South Africa. 5th IAS Conference on HIV Treatment, Pathogenesis and Prevention, Cape Town, abstract TuPdB106, 2009.

Suchindran S, Brouer E, Van Rie A Is HIV infection a risk factor for multi-drug resistant tuberculosis? A systematic review. PloS One, 4(5), May 2009.