Antiretroviral Therapy and TB Notification Rates in a High HIV Prevalence South African Community
Antiretroviral therapy (ART) has been proposed as an intervention for reducing tuberculosis (TB) burdens in areas with high HIV prevalence. However, little data is available on the impact of ART on population-level TB.
Trends in adult TB case fatality and notifications were assessed before and during increasing ART coverage in a well-defined periurban community, from 1997 to 2008. Mean changes in TB rates were measured using linear autoregression models. ART coverage increased from 1% in 2003 to 5%, 13%, and 21% of HIV-infected population in 2004, 2005, and 2008, respectively.
From 1997 to end of 2004 TB notification rates increased by an average of 187 cases/100,000/year (P < 0.001), reaching a peak of 2536/100,000 in 2005. From 2005 to 2008, TB notification rates declined by approximately 202 cases/100,000/year (P < 0.001). TB rates were initially stable in HIV-uninfected individuals, but declined moderately from 2005. TB rates declined in HIV-infected adults from 6513/100,000 in 2005 to 4741/100,000 in 2008. The predominant decline in TB notifications occurred among HIV-infected patients receiving ART (1156 cases/100,000/year) and was less marked in those not receiving ART (416 cases/100,000/year). Similarly, TB case fatality was constant for HIV-uninfected individuals, but declined in HIV-infected individuals from 23% in 2002 to 8% in 2008 (P = 0.01).
In this community heavily affected by both HIV and TB epidemics, rapid and high ART coverage was associated with significant reductions in TB notifications and TB-associated case fatality.
Available from: PubMed Central
- "Antiretroviral therapy has been shown to substantially decrease tuberculosis incidence in persons living with HIV, particularly when it is initiated while CD4 counts are still comparatively high , , . Consistent with this effect, we observed that the scale-up in antiretroviral therapy programs in Kenya coincided with a more pronounced decline in tuberculosis incidence during 2007–2012 among adults with HIV than among adults without HIV, although we cannot conclude causality based on our analysis. "
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In Kenya, the comparative incidences of tuberculosis among persons with and without HIV have not been described, and the differential impact of public health interventions on tuberculosis incidence in the two groups is unknown.
We estimated annual tuberculosis incidence stratified by HIV status during 2006–2012 based on the numbers of reported tuberculosis patients with and without HIV infection, the prevalence of HIV infection in the general population, and the total population. We also made crude estimates of annual tuberculosis incidence stratified by HIV status during 1998–2012 by assuming a constant ratio of HIV prevalence among tuberculosis patients compared to the general population.
Tuberculosis incidence among both adults with HIV and adults without HIV increased during 1998–2004 then remained relatively stable until 2007. During 2007–2012, tuberculosis incidence declined by 28–44% among adults with HIV and by 11–26% among adults without HIV, concurrent with an increase in antiretroviral therapy uptake. In 2012, tuberculosis incidence among adults with HIV (1,839–1,936 cases/100,000 population) was still eight times as high as among adults without HIV (231–238 cases/100,000 population), and approximately one third of tuberculosis cases were attributable to HIV.
Although tuberculosis incidence has declined among adults with and without HIV, the persistent high incidence of tuberculosis among those with HIV and the disparity between the two groups are concerning. Early diagnosis of HIV, early initiation of antiretroviral therapy, regular screening for tuberculosis, and isoniazid preventive therapy among persons with HIV, as well as tuberculosis control in the general population, are required to address these issues.
Available from: Robin Wood
- "The HIV prevalence measured in 2005 and 2010 was 23% among adults [11,12] and was 5% among secondary school-going adolescents in 2009 . TB notification was mandatory throughout the study period, and TB rates are exceptionally high in this community, ±2,000/100,000 since 2006 . There is a mean annual risk of TB infection of 4.1%, and we have previously shown that the annual incidence of TB infection increased with age among children and adolescents . "
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ABSTRACT: Tuberculosis (TB) transmission rates are exceptionally high in endemic TB settings. Adolescence represents a period of increasing TB infection and disease but little is known as to where adolescents acquire TB infection. We explored the relationship between residential exposure to adult TB cases and infection in children and adolescents in a South African community with high burdens of TB and HIV.
TB infection data were obtained from community, school-based tuberculin skin test (TST) surveys performed in 2006, 2007 and 2009. A subset of 2007 participants received a repeat TST in 2009, among which incident TB infections were identified. Using residential address, all adult TB cases notified by the community clinic between 1996 and 2009 were cross-referenced with childhood and adolescent TST results. Demographic and clinic data including HIV status were abstracted for TB cases. Multivariate logistic regression models examined the association of adult TB exposure with childhood and adolescent prevalent and incident TB infection.
Of 1,100 children and adolescents included in the prevalent TB infection analysis, 480 (44%) were TST positive and 651 (59%) were exposed to an adult TB case on their residential plot. Prevalent TB infection in children aged 5-9 and 10-14 years was positively associated with residential exposure to an adult TB case (odds ratio [OR]:2.0; 95% confidence interval [CI]: 1.1-3.6 and OR:1.5; 95% CI: 1.0-2.3 respectively), but no association was found in adolescents >=15 years (OR:1.4; 95% CI: 0.9-2.0). HIV status of adult TB cases was not associated with TB infection (p = 0.62). Of 67 previously TST negative children, 16 (24%) converted to a positive TST in 2009. These incident infections were not associated with residential exposure to an adult TB case (OR: 1.9; 95% CI: 0.5-7.3).
TB infection among young children was strongly associated with residential exposure to an adult TB case, but prevalent and incident TB infection in adolescents was not associated with residential exposure. The HIV-status of adult TB cases was not a risk factor for transmission. The high rates of TB infection and disease among adolescents underscore the importance of identifying where infection occurs in this age group.
Available from: Rony Zachariah
- "At the individual level, these beneficial effects increase with length of time on ART, although they never decrease to a level that approaches the rates of TB seen in patients without HIV-infection [18,19]. At the programme level, it has also been shown in rural Malawi  and Cape Town, South Africa , that when ART coverage in a population reaches a high level of coverage, TB notification rates in that population decrease, and in Malawi, this reduction was noted for both new and recurrent TB (Table 5) . "
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ABSTRACT: Every year, HIV-associated tuberculosis (TB) deprives 350,000 mainly young people of productive and healthy lives.People die because TB is not diagnosed and treated in those with known HIV infection and HIV infection is not diagnosed in those with TB. Even in those in whom both HIV and TB are diagnosed and treated, this often happens far too late. These deficiencies can be addressed through the application of new scientific evidence and diagnostic tools.
A strategy of starting antiretroviral therapy (ART) early in the course of HIV infection has the potential to considerably reduce both individual and community burden of TB and needs urgent evaluation for efficacy, feasibility and broader social and economic impact. Isoniazid preventive therapy can reduce the risk of TB and, if given strategically in addition to ART, provides synergistic benefit. Intensified TB screening as part of the "Three I's" strategy should be conducted at every clinic, home or community-based attendance using a symptoms-based algorithm, and new diagnostic tools should increasingly be used to confirm or refute TB diagnoses. Until such time when more sensitive and specific TB diagnostic assays are widely available, bolder approaches such as empirical anti-TB treatment need to be considered and evaluated. Patients with suspected or diagnosed TB must be screened for HIV and given cotrimoxazole preventive therapy and ART if HIV-positive. Three large randomized trials provide conclusive evidence that ART initiated within two to four weeks of start of anti-TB treatment saves lives, particularly in those with severe immunosuppression. The key to ensuring that these collaborative activities are delivered is the co-location and integration of TB and HIV services within the health system and the community.
Progress towards reducing HIV-associated TB deaths can be achieved through attention to simple and deliverable actions on the ground.
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