Potential utility of empirical tuberculosis treatment for HIV-infected patients with advanced immunodeficiency in high TB-HIV burden settings.

The human immunodeficiency virus (HIV) and HIV-associated tuberculosis (TB-HIV) epidemics remain uncontrolled in many resource-limited regions, especially in sub-Saharan Africa. The scale of these epidemics requires the consideration of innovative bold interventions and 'out-of-the-box' thinking. To this end, a symposium entitled 'Controversies in HIV' was held at the 40th Union World Conference on Lung Health in Cancun, Mexico, in December 2009. The first topic debated, entitled 'Annual HIV testing and immediate start of antiretroviral therapy for all HIV-infected persons', received much attention at international conferences and in the literature in 2009. The second topic forms the subject of this article. The rationale for the use of empirical TB treatment is premised on the hypothesis that in settings worst affected by the TB-HIV epidemic, a subset of HIV-infected patients have such a high risk of undiagnosed TB and of associated mortality that their prognosis may be improved by immediate initiation of empirical TB treatment used in conjunction with antiretroviral therapy. In addition to morbidity and mortality reduction, additional benefits may include prevention of nosocomial TB transmission and TB preventive effect. Potential adverse consequences, however, may include failure to consider other non-TB diagnoses, drug co-toxicity, compromised treatment adherence, and logistical and resource challenges. There may also be general reluctance among national TB programmes to endorse such a strategy. Following fruitful debate, the conclusion that this strategy should be carefully evaluated in randomised controlled trials was strongly supported. This paper provides an in-depth consideration of this proposed intervention.

Initiating antiretroviral treatment in a resource-constrained setting: does clinical staging effectively identify patients in need?

In industrialized countries, the initiation of antiretroviral therapy (ART) is based on virological, immunological and clinical markers. The objective of this study was to identify treatment gaps when ART initiation is based on clinical staging alone. The method employed was a retrospective study of 5784 patients enrolled in an HIV treatment programme in two urban and two rural sites in Ghana. Of the patients, 29.5% were in clinical Stages I and II and had a CD4+ T-lymphocyte count less than 200 cells/mm(3). Significantly more patients in clinical Stage I from urban sites (37.0%) had a CD4+ T-lymphocyte count less than 200 cells/mm(3) as compared with patients from rural sites (23.8%) (P value <0.05). In addition, more men (39.9%) in clinical Stage I had a CD4+ T-lymphocyte count less than 200 cells/mm(3) when compared with women (27.4%) (P value <0.05). In conclusion, clinical staging cannot identify a relatively large number of patients who need ART. A wider availability of CD4+ T-lymphocyte count testing will optimize the identification of patients eligible for ART.

Normal CD4+ T lymphocyte levels in HIV seronegative individuals in the Manya/Yilo Krobo communities in the Eastern region of Ghana.

The goal of this study was to determine the normal levels of CD4+ T lymphocytes in healthy individuals who were HIV seronegative in the Manya and Yilo Krobo Districts of Ghana's Eastern Region. This enabled comparisons with normal CD4 count ranges established by the World Health Organization (WHO). The study population consisted of 249 HIV-seronegative clients from a mobile free Voluntary Counseling and Testing (VCT) service in communities of the two districts during a one-month period. The mean CD4 count of these individuals was 1067 cells/microl with women demonstrating higher baseline CD4 counts than men. This study found a WHO comparable HIV seronegative baseline CD4 count as well as gender-based differences in the CD4 count and CD4/CD8 ratio. Establishment of the adult baseline for the country provides important demographic data and indicates the appropriateness of current global treatment guidelines with regards to CD4 levels in Ghana.

Trend in HIV prevalence among tuberculosis patients in Tanzania, 1991-1998.

OBJECTIVE: To determine the trend in human immunodeficiency virus (HIV) prevalence among tuberculosis patients in Tanzania and estimate what proportion of the increase in notification rates between the surveys was directly attributable to HIV infection. METHODS: Consecutive tuberculosis patients were enrolled over 6-month periods in most regions. Demographic and clinical data were collected on standard forms and a single HIV ELISA test performed. Trends in tuberculosis incidence were estimated from regional notification data. RESULTS: Of 10612 eligible tuberculosis patients, 44% had HIV infection, compared with 32% in the previous survey. The largest increase was observed in the youngest birth cohorts, suggesting active HIV transmission. Approximately 60% of the increase in notification rates of smear-positive tuberculosis between surveys was directly attributable to HIV infection. CONCLUSION: The HIV epidemic has had a strong influence on tuberculosis incidence. However, since 1995, tuberculosis notification data have increased less steeply, AIDS notifications have gone down, and HIV prevalence in blood donors has not increased a great deal. Another survey among tuberculosis patients in 5 years' time may show whether the HIV epidemic in Tanzania has reached a maximum or steady state.

Tuberculosis case fatality rates in high HIV prevalence populations in sub-Saharan Africa.

BACKGROUND: Tuberculosis is a leading cause worldwide of morbidity and mortality among HIV-infected people. The HIV era has seen a dramatic increase of the tuberculosis case fatality rate (CFR) in high HIV prevalence populations. Providing care for HIV-infected people must include measures to tackle this high tuberculosis CFR. AIMS: To analyse the extent of the increased tuberculosis CFR in high HIV prevalence populations in sub-Saharan Africa, the reasons for this increase and the causes of death, in order to identify possible ways of tackling this problem. METHODS: References were obtained by searching the MEDLINE on 'tuberculosis', 'HIV infection', and 'mortality' (MesH or textword). In addition, available data from National Tuberculosis Programme reports were reviewed. FINDINGS: Tuberculosis CFR is closely linked to HIV prevalence. Limited autopsy data suggest that death from HIV-related diseases other than tuberculosis is probably the main reason for the increased CFR in HIV-infected tuberculosis patients. Among HIV-infected tuberculosis patients, the higher tuberculosis CFR in sputum smear-negative and extrapulmonary than in sputum smear-positive tuberculosis cases can also be attributed to misdiagnosis of HIV-related diseases as tuberculosis. The adverse effect of the HIV/AIDS epidemic on general health service performance probably accounts for the higher tuberculosis CFR among HIV-negative tuberculosis patients in high prevalence populations than that in low HIV-prevalence populations. CONCLUSION: Tackling the problem of the increased tuberculosis CFR in high HIV prevalence populations requires collaboration between tuberculosis control and HIV/AIDS programmes in implementing measures such as improved health services, tuberculosis and HIV control services, preventive treatment for HIV-related diseases and anti-HIV treatment.

Impact of HIV infection on the development, clinical presentation, and outcome of tuberculosis among children in Abidjan, Côte d'Ivoire.

OBJECTIVE: To assess the impact of HIV infection upon the development, clinical presentation, and outcome of tuberculosis (TB) among children. DESIGN: Case-control study and prospective cohort study. METHODS: From March 1994 to November 1995, children aged 0-9 years with newly diagnosed TB were enrolled at the two outpatient TB centers and the two principal university hospitals in Abidjan, Côte d'Ivoire. Children were examined, blood samples were collected for HIV serology and lymphocyte phenotyping, chest radiography was performed, and gastric aspirates and sputum samples were collected for acid-fast bacilli smear and culture. Children were then followed every 2 months during a standard 6-month course of anti-TB therapy. To examine risk factors for TB, age- and sex-matched healthy control children were enrolled from among the siblings of children referred for TB skin testing. RESULTS: Overall, 161 children with TB were enrolled, including 39 (24%) with culture-confirmed pulmonary TB, 80 (50%) with clinically diagnosed pulmonary TB, and 42 (26%) with extrapulmonary TB. Children with TB were significantly more likely than 161 control children to be HIV-seropositive (19 versus 0%), to have a past TB contact (55 versus 16%) and to live in very low socioeconomic status housing (24 versus 6%). No significant differences between HIV-seropositive and seronegative children were found in the distribution of radiologic abnormalities for pulmonary TB or in the site of extrapulmonary TB. The mortality rate in HIV-seropositive children was significantly higher than in seronegative children (23 versus 4%; relative risk, 3.6; 95% confidence interval, 2.0-6.6), and all deaths in HIV-seropositive children with available lymphocyte subtyping results occurred in those with a CD4 percentage of < 10%. CONCLUSIONS: This study documents the importance of HIV infection as an independent risk factor for the development of TB in children, and demonstrates that HIV-related immunosuppression is a critical risk factor for mortality in this population.