TB/HIV in Practice

TB/HIV is a monthly feature on TB/HIV issues. It is kindly supported by the STOP TB department of the World Health Organization.

TB/HIV news from the Fifth International AIDS Society conference

Antiretroviral roll-out results in major TB decline in South African study

by Keith Alcorn

The roll out of antiretroviral treatment to cover 90% of eligible people has resulted in a significant decline in new cases of tuberculosis in a South African township, demonstrating for the first time the potential of antiretroviral treatment to make major inroads into the burden of TB in high prevalence countries.

New TB cases fell by 60% in HIV-positive people in just three years, contributing to a 20% decline in TB cases in the township between 2005 and 2008.

The findings were presented by Dr Keren Middelkoop of the Desmond Tutu HIV Centre at the University of Cape Town as a late breaker at the Fifth International AIDS Society conference in Cape Town.

The study measured changes in TB prevalence in the population of a single township served by one health centre, in order to capture all cases of TB. The research group conducted cross-sectional studies in 2005 and 2008.

ART coverage in the community expanded from approximately 12% of the HIV-positive population on antiretroviral therapy in 2005 to 24% on treatment by 2007. Ninety per cent of those qualifying for antiretroviral treatment under South African guidelines (a CD4 count below 200 or active TB) were receiving it in the township by 2008.

A random sample of 762 individuals was included in the study in 2005 and 1251 in 2008. They each provided two sputum samples and completed a TB history questionnaire. All the individuals also had an anonymous, oral HIV test, the result of which was linked to their sputum samples.

Results of the anonymous HIV tests showed that 25% of the study participants were HIV-positive.

In 2005, 4% of HIV-positive individuals were receiving TB treatment compared to 1% of HIV-negative individuals. However, in 2008 approximately 1% of both HIV-positive and HIV-negative study participants were taking TB therapy.

Similarly, in 2005 there was a significantly higher prevalence of undiagnosed TB amongst HIV-positive patients than HIV-negative individuals (5.2% vs. 0.5%). In 2008, however, only 3.6% of HIV-positive individuals had undiagnosed TB compared to 1.1% of HIV-negative individuals.

Overall TB prevalence amongst patients with HIV fell from 9.2% in 2005 to 3.6% in 2008.

After adjusting for age, sex and HIV status, there was a significant fall in TB prevalence in 2008 compared to 2005 (p = 0.02). This decrease was driven by a fall in HIV prevalence amongst the patients with HIV, most notably the fall in the prevalence of undiagnosed TB.

When TB notifications were analysed according to antiretroviral treatment status, it became clear that virtually all of the decrease occurred in people receiving ART, in whom the notification rate fell from 8,000 cases per 100,000 to approximately 2,500 cases per 100,000, a reduction of almost 60%. In contrast the TB notification rate remained almost stable at around 6,500 cases per 100,000 in untreated people with HIV.

The investigators ruled out a higher death rate in people with HIV as the reason for the decline, since the decline occurred in people receiving antiretroviral treatment. Nor could the decline be explained by changes in local TB management or emigration out of the district, since neither changed during the study period.

At this point the authors cannot determine whether the effect of antiretroviral therapy on TB prevalence is a function of a lower rate of transmission (due to the lower population burden) or of a reduction in TB reactivation, and they plan further analyses to shed more light on the question.

Reference

Middelkoop K et al. Widespread ART is associated with decline in TB prevalence. 5^th IAS Conference on HIV Treatment, Pathogenesis and Prevention, Cape Town, abstract WeLBB105, 2009.

Further information

A webcast of the conference session in which Keren Middelkoop presented is available on the IAS 2009 website here.

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

by Lesley Odendal

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.

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.

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.

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.

Resurgence of TB, diarrhoeal disease and malnutrition in Zimbabwe due to hyperinflation and economic collapse

by Lesley Odendal

The economic crisis since 2000 in Zimbabwe has led to a rapid rise in TB cases and rising rates of malnutrition. However, it appears that HIV prevalence in pregnant women is decreasing, Dr M Silverman reported to the Fifth International AIDS Society Conference in Cape Town.

This study is the first to demonstrate an association between rising TB incidence and national economic decline in the absence of armed conflict.

Zimbabwe has undergone an economic collapse since 2000 characterised by political crisis, hyperinflation and a real GDP reduction of 40% between 2000 and 2007 and a further 14% decrease in 2008.

Since 1995 to 31 March 2009 information has been prospectively collected on diagnoses made at a rural mission hospital, Howard Hospital, in Zimbabwe. National surveillance data showing a decline in TB incidence since2004 is likely to be skewed, given that most health care facilities shut down during the peak of the economic crisis.

Howard Hospital is one of the few mission hospitals that remained functioning and hence its data are likely to be more reliable for determining burden of disease.

During the period of the study from 1995 to 2009, 8,770 cases of tuberculosis (TB), 6, 695 cases of nutritional diseases and 27 399 cases of diarrhoea were diagnosed. 81.8% of the TB cases were coinfected with HIV.

Between 1995 and 2001, the study found that TB incidence had risen gradually from 176 per 100,000 to 281 per 100,000, however this finding correlated with the rising HIV epidemic in Zimbabwe.

However, a further rapid rise in TB incidence to 426 per 100 000 corresponded with the onset of hyperinflation between 2003 and 2007 (p<0.05). During this period there was also an increase in the incidence of pellagra, kwashiorkor and diarrhoeal illnesses.

TB incidence remained stable between 2003 and 2007, but rose a further 35% in 2008 to 556 per 100 000 (p<0.01), with a further 15% increase occurring in the first five months of 2009.

Monthly time-series analyses showed that increasing economic inflation was associated with subsequent increases in TB incidence.

A seasonal pattern in TB incidence was observed by the investigators.

Diagnoses were lowest at harvest time and in the following three months, when food was plentiful, but increased significantly when food was scarce (p < 0.01). The rising TB incidence did not reflect patterns of migration as all data collected only reflected patients already living in the catchment area of the hospital.

A total of 18,746 antenatal HIV tests were conducted at the mission hospitals during the period of the study and 3,636 were positive. HIV prevalence at antenatal clinics fell significantly during the period of the study from 23% in 2001 to 11% at the end of 2008 (p < 0.01). This decline was seen even though HIV testing rates remained high and stable at above 90%.

This decline in HIV seroprevalence during the peak economic crisis year when public health programmes had essentially collapsed in Zimbabwe suggests that economic decline may be decreasing HIV seroprevalence in pregnant women.

Investigators suggested that this may be due a decrease in sexual mixing and thus lower rates of infection, or possibly increased death rates or decreased fertility in HIV-positive women due to lack of nutrition and starvation.

Reference

Silverman M et al. An epidemic of tuberculosis in association with HIV, malnutrition and hyperinflation in Zimbabwe. 5th IAS Conference on HIV Treatment, Pathogenesis and Prevention, Cape Town, abstract TuPdB105, 2009.

Further information

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

HIV & AIDS Treatment in Practice #143: IAS 2009 conference news

The Fifth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention took place July 19-22 in Cape Town, South Africa.

More than any other recent international conference, IAS 2009 was dominated by important research from sub-Saharan Africa that will have significant implications for the way that treatment and care are delivered in resource-limited settings.

This edition reproduces in full news coverage published during the conference by aidsmap.com, the official online news provider for the IAS 2009 conference. It covers news stories in the following categories:

• Prevention of mother to child transmission
• Treatment and care for children
• The results of the DART study
• Antiretroviral treatment
• Care
• Biomedical prevention

Future editions of HATIP will be looking in more detail at some of the major topics of the conference, including:

• What will the results of studies on antiretroviral therapy during pregnancy and breastfeeding mean for frontline services and for women with HIV?
• What do the results of the DART study mean for treatment monitoring practices in resource-limited settings?