Elsevier

The Lancet

Volume 359, Issue 9323, 15 June 2002, Pages 2059-2064
The Lancet

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Effect of highly active antiretroviral therapy on incidence of tuberculosis in South Africa: a cohort study

https://doi.org/10.1016/S0140-6736(02)08904-3Get rights and content

Summary

Background

Studies of the effect of highly active antiretroviral therapy (HAART) on the risk of HIV-1-associated tuberculosis have had variable results. We set out to determine the effect of HAART on the risk of tuberculosis in South Africa.

Methods

We compared the risk of tuberculosis in 264 patients who received HAART in phase III clinical trials and a prospective cohort of 770 non-HAART patients who were attending Somerset Hospital adult HIV clinic, University of Cape Town, between 1992 and 2001. Poisson regression models were fitted to determine risk of tuberculosis; patients were stratified by CD4 count, WHO clinical stage, and socioeconomic status.

Findings

HAART was associated with a lower incidence of tuberculosis (2·4 vs 9·7 cases per 100 patient-years, adjusted rate ratio 0·19 [95% CI 0·09–0·38]; p<0·0001). This finding was apparent across all strata of socioeconomic status, baseline WHO stage, and CD4 count, except in patients with CD4 counts of more than 350 cells/μL. The number of tuberculosis cases averted by HAART was greatest in patients with WHO stage 3 or 4 (18·8 averted cases per 100 patient-years, adjusted rate ratio 0·22 [0·09–0·41]; p=0·03) and in those with CD4 counts of less than 200 cells/μL (14·2 averted cases per 100 patient-years, adjusted rate ratio 0·18 [0·07–0·47]; p<0·0001).

Interpretation

HAART reduced the incidence of HIV-1-associated tuberculosis by more than 80% (95% CI 62–91) in an area endemic with tuberculosis and HIV-1. The protective effect of HAART was greatest in symptomatic patients and those with advanced immune suppression.

Introduction

More than 70% of the 36·1 million HIV-1-infected individuals worldwide live in sub-Saharan Africa, and a high proportion of these are co-infected with tuberculosis.1, 2 An accelerated course of HIV-1 infection after the onset of tuberculosis has been reported in many studies.3, 4, 5, 6

Tuberculosis is the leading cause of morbidity and mortality among HIV-1-infected patients in sub-Saharan Africa.7, 8, 9 Unlike other HIV-1-related opportunistic infections, tuberculosis occurs at all levels of CD4 count,9, 10, 11 is infectious, and its prevention is a major public-health priority.

Tuberculosis control programmes based on passive case finding and treatment of sputum-smear-positive disease by short-courses of directly observed chemotherapy (DOTS) have been successful in developed countries. However, these strategies have failed to achieve similar success in countries with high burdens of HIV-1 infection.12, 13 Consequently, WHO has formulated a strategic framework aimed at functional integration of control programmes for tuberculosis and HIV/AIDS.14

The survival benefits associated with highly active antiretroviral therapy (HAART) are well documented; however, studies assessing the effect of HAART on tuberculosis have shown variable results. Although some studies have shown that HAART can reduce the risk of tuberculosis by more than 80%,15, 16, 17 others have reported no significant reduction.18, 19 No similar studies have been done in sub-Saharan Africa because only a tiny minority of the population presently has access to HAART. The UN has mobilised the Great Global Alliance to facilitate increased access to antiretroviral therapy in resource-limited settings.20

We did an observational study to compare the risk of tuberculosis in indigent cohorts of HIV-1-infected patients without access to HAART and in those receiving this treatment through participation in phase III randomised trials at a public health-care facility in Cape Town, South Africa.

Section snippets

Patients

New Somerset Hospital HIV Clinic, University of Cape Town, South Africa, is a major public health-care facility dedicated to HIV-1-infected patients in Cape Town. It was established in 1986, and serves largely indigent patients who are referred to the clinic from a wide range of primary health-care facilities in Cape Town. Antiretroviral therapy is not available in the public sector in South Africa, and patients access HAART through participation in clinical trials. Patients who expressed

Results

1085 patients in the non-HAART cohort and 270 patients in the HAART cohort were studied. 315 patients were excluded from the non-HAART cohort: 79 were on antiretroviral monotherapy or dual therapy, isoniazid prophylaxis, or both; 222 presented with tuberculosis at their initial clinic visit; and 14 incident cases received tuberculosis chemotherapy but did not meet the tuberculosis case definition. The remaining 770 patients were included in the analysis. Of the 270 patients recruited in the

Discussion

We have shown a substantial reduction in tuberculosis incidence attributable to HAART in HIV-1-infected individuals in sub-Saharan Africa. This study differs from previous reports because the high frequency of tuberculosis in our cohort allowed quantification of the protective effect of HAART at the different stages of HIV-1 disease. The effect of HAART was significant across all the baseline immunological, clinical, and socioeconomic variables in our cohort, except in patients with CD4 counts

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