Tuberculosis In HIV-infected Persons Research Articles

Prevalence of Disseminated Tuberculosis in HIV-Infected Persons Admitted with Sepsis at Moi Teaching and Referral Hospital, Eldoret, Kenya

Background: Disseminated Tuberculosis (TB) is associated with high morbidity and mortality in HIV-infected persons. The clinical presentation mimics that of sepsis hence requires a high index of suspicion to make a diagnosis. Gold standard of diagnosis is blood cultures that have a long incubation period thus delay in initiation of treatment. Current burden of disseminated TB in adult HIV-infected persons is not known in Western Kenya. Objectives: To determine the prevalence of disseminated TB and the clinical characteristics of HIV-infected persons with disseminated TB. Methods: A cross sectional study carried out at the Moi Teaching and Referral Hospital (MTRH) medical wards. Within 24 hours of admission the interviewer administered the questionnaire, and blood and urine samples were collected. Independent variables were summarized using frequencies (%), mean (SD) and median (IQR); dependent variables were analyzed using Student t-test, Chi square and Wilcoxon rank sum test. A p ≤ 0.05 was considered significant. Results: From April to September 2017, 298 participants were recruited; 58% (173) were female, mean age was 41.68 (SD 11.72). The prevalence of disseminated TB was 26% (95% CI 21.2-31.4). The LAM positive group had a lower hemoglobin level of 9.71g/dl versus 10.47g/dl in the LAM negative group (p0.04). Sixty percent (178) of the participants had lymphopenia with 31% of them having LAM antigen positive versus 69% having LAM antigen negative (p 0.04). One hundred and ninety-three participants (193) were not on antiretroviral therapy with 30% of them having LAM antigen positive versus 70% of them having LAM antigen negative (p 0.02). Conclusion: The prevalence of disseminated TB in this setting was 26%. Possible factors associated with LAM antigen positivity included anemia, lymphopenia and not on antiretroviral therapy. Recommendations: LAM antigen assay should be a routine diagnostic test in HIV-infected persons admitted with sepsis

Manifestations of epidemic process of tuberculosis among HIV-infected patients and dependence of infection frequency on immunodeficiency level and HIV viral load

Objective. To assess the manifestations of the epidemic process of tuberculosis (TB) in HIV-infected persons and the frequency of infection depending on the level of immunodeficiency and viral load.
 Materials and methods. The epidemiological manifestations of TB incidence among HIV-infected and HIV-negative population of the Perm Region for 20142019 were studied. The frequency of TB in HIV-infected patients was determined depending on the level of immunodeficiency (96 patients) and viral load (61 patients).
 Results. On average, the incidence of TB among HIV-infected persons was by 36 times higher than that of noninfected persons. Among those infected and noninfected with HIV, TB was registered significantly more often among adults, and mainly men. The incidence of TB among HIV-infected persons is higher among urban population, while HIV-negative among rural residents. The incidence of TB in HIV-infected persons increases with an increase in the immunodeficiency and viral load.
 Conclusions. Persons with HIV infection are at risk for TB. The incidence of TB in HIV-infected persons increases with an increase in immunodeficiency and viral load.

Th22 Cells Are a Major Contributor to the Mycobacterial CD4+ T Cell Response and Are Depleted During HIV Infection.

HIV-1 infection substantially increases the risk of developing tuberculosis (TB). Mechanisms such as defects in the Th1 response to Mycobacterium tuberculosis in HIV-infected persons have been widely reported. However, Th1-independent mechanisms also contribute to protection against TB. To identify a broader spectrum of defects in TB immunity during HIV infection, we examined IL-17A and IL-22 production in response to mycobacterial Ags in peripheral blood of persons with latent TB infection and HIV coinfection. Upon stimulating with mycobacterial Ags, we observed a distinct CD4+ Th lineage producing IL-22 in the absence of IL-17A and IFN-γ. Mycobacteria-specific Th22 cells were present at high frequencies in blood and contributed up to 50% to the CD4+ T cell response to mycobacteria, comparable in magnitude to the IFN-γ Th1 response (median 0.91% and 0.55%, respectively). Phenotypic characterization of Th22 cells revealed that their memory differentiation was similar to M. tuberculosis-specific Th1 cells (i.e., predominantly early differentiated CD45RO+CD27+ phenotype). Moreover, CCR6 and CXCR3 expression profiles of Th22 cells were similar to Th17 cells, whereas their CCR4 and CCR10 expression patterns displayed an intermediate phenotype between Th1 and Th17 cells. Strikingly, mycobacterial IL-22 responses were 3-fold lower in HIV-infected persons compared with uninfected persons, and the magnitude of responses correlated inversely with HIV viral load. These data provide important insights into mycobacteria-specific Th subsets in humans and suggest a potential role for IL-22 in protection against TB during HIV infection. Further studies are needed to fully elucidate the role of IL-22 in protective TB immunity.

Effect of m-health technology on knowledge and practice of the tuberculosis preventive therapy guideline among health workers in Ebonyi State, Nigeria

Background: Prophylaxis with isoniazid has been shown to reduce the incidence of tuberculosis in HIV infected persons. The study aimed to determine the effect of mobile phone based education and reminders on health worker knowledge and practice of tuberculosis preventive therapy (TPT) guidelines. Methods and materials: The study was carried out in six health facilities in Ebonyi state, and employed a quasi-experimental design without randomization. Three health facilities were assigned to intervention and control arms each. Simple random sampling was used to select the participating health facilities and all eligible health workers (45 and 41 in intervention and control arms respectively) who had worked in the HIV clinics for not less than six months were selected. A pre-tested self-administered questionnaire was used for the survey. The intervention consisted of mobile phone messages and reminders on the tuberculosis preventive therapy guideline to the health workers. Data was analysed using Statistical Package for Social Sciences (IBM-SPSS) version 20. Chi square test was carried out and analytical decisions were taken at p < 0.05. Ethical approval was obtained from the research and ethics committee of Alex-Ekwueme Federal University Teaching Hospital, Abakaliki, and written informed consent was obtained from the participants. Results: Mean age of the health workers was 40.43 ± 7.16 and 33.15 ± 8.56 in the intervention and control arms respectively. At baseline, majority of the health workers 54.5% and 63.4% in intervention and control arms respectively had high knowledge level. At post-intervention, significantly higher proportion of health workers in the intervention arm (90.2%) had high knowledge level (p < 0.0001). For practice of the TPT guideline, 61.4% and 90.2% of health workers had good practice in intervention and control arms respectively. At post-intervention, there was a statistically significant increase in the proportion of respondents who had good practice within the intervention arm (p = 0.01). Conclusion: Mobile phone messaging has been shown in this study to be useful in improving knowledge and practice of tuberculosis preventive therapy guideline among health workers and should be considered for inclusion in the guideline and policy for prevention of tuberculosis among HIV patients.

Tuberculosis in combination with HIV infection

In Ukraine, epidemics of two socially dangerous diseases tuberculosis (TB) and human immunodeficiency virus (HIV infection) are developing at an accelerated pace. According to the literature, more than 30 % of HIV-infected people get TB and about 40—80 % of those who get sick die.Objective — to assess the epidemic situation of tuberculosis, HIV infection, tuberculosis in combination with HIV infection in Ukraine. To study the features of the clinic, diagnostics, course and treatment of tuberculosis in HIV-infected people.Materials and methods. Analysis of literature sources on HIV-associated tuberculosis over the past 10 years.Results and discussion. The main epidemiological indicators of tuberculosis, HIV infection and the combination of tuberculosis with HIV infection in Ukraine are described. The peculiarities of the clinical, radiological picture and course of tuberculosis in HIV-infected persons depending on the stage of HIV infection are analyzed. TB still remains the leading cause of death for HIV patients.Conclusions. Against the background of HIV infection, the risk of TB infection and reactivation of tuberculous endogenous infection increases significantly. TB/HIV/AIDS co-infection is characterized by the development of multiorgan tuberculosis. Diagnosis of tuberculosis on the background of HIV infection, especially with CD4+ T-lymphocytes < 200 in 1 mm3 of blood, is much more difficult. TB treatment for TB/HIV co-infection can only be successful with antiretroviral therapy. Antiretroviral therapy and co-trimoxazole are prescribed regardless of the number of CD4+ T-lymphocytes.

Effectiveness of the treatment of generalized tuberculosis in HIV-infected patients

Abstract. The treatment of tuberculosis in HIV-infected persons is a complex task and often requires intensive therapy with intravenous administration of antituberculosis drugs, especially in generalized forms, malabsorption, presence of enteropathy, hepatitis B and C, severe condition. One of the dangerous forms of tuberculosis in HIV-infected people is meningeal tuberculosis. In these cases, the effectiveness of treatment for HIV-positive patients depends on timely detection, diagnosis of resistance to antituberculosis drugs, presence of other opportunistic diseases. Here is an example of treating a HIV-positive patient with miliary tuberculosis with lung damage, lymph nodes and meningeal tuberculosis caused by a multiresistant strain of tuberculosis. The treatment was performed taking into account drugs that cross the blood-brain barrier, drug sensitivity test, immunosuppression and the presence of malabsorption. Timely intensive therapy with intravenous administration of medications for medical sensitivity allowed to obtain positive dynamics and cure the patient in the short term.

Performance of Clinical Screening Algorithms for Tuberculosis Intensified Case Finding among People Living with HIV in Western Kenya.

ObjectiveTo assess the performance of symptom-based screening for tuberculosis (TB), alone and with chest radiography among people living with HIV (PLHIV), including pregnant women, in Western Kenya.DesignProspective cohort studyMethodsPLHIV from 15 randomly-selected HIV clinics were screened with three clinical algorithms [World Health Organization (WHO), Ministry of Health (MOH), and “Improving Diagnosis of TB in HIV-infected persons” (ID-TB/HIV) study], underwent chest radiography (unless pregnant), and provided two or more sputum specimens for smear microscopy, liquid culture, and Xpert MTB/RIF. Performance of clinical screening was compared to laboratory results, controlling for the complex design of the survey.ResultsOverall, 738 (85.6%) of 862 PLHIV enrolled were included in the analysis. Estimated TB prevalence was 11.2% (95% CI, 9.9–12.7). Sensitivity of the three screening algorithms was similar [WHO, 74.1% (95% CI, 64.1–82.2); MOH, 77.5% (95% CI, 68.6–84.5); and ID-TB/HIV, 72.5% (95% CI, 60.9–81.7)]. Sensitivity of the WHO algorithm was significantly lower among HIV-infected pregnant women [28.2% (95% CI, 14.9–46.7)] compared to non-pregnant women [78.3% (95% CI, 67.3–86.4)] and men [77.2% (95% CI, 68.3–84.2)]. Chest radiography increased WHO algorithm sensitivity and negative predictive value to 90.9% (95% CI, 86.4–93.9) and 96.1% (95% CI, 94.4–97.3), respectively, among asymptomatic men and non-pregnant women.ConclusionsClinical screening missed approximately 25% of laboratory-confirmed TB cases among all PLHIV and more than 70% among HIV-infected pregnant women. National HIV programs should evaluate the feasibility of laboratory-based screening for TB, such as a single Xpert MTB/RIF test for all PLHIV, especially pregnant women, at enrollment in HIV services.

High prevalence of being Overweight and Obese HIV-infected persons, before and after 24months on early ART in the ANRS 12136 Temprano Trial.

BackgroundHIV is usually associated with weight loss. World health Organization (WHO) recommends early antiretroviral (ART) initiation, but data on the progression of body mass index (BMI) in participants initiating early ART in Africa are scarce.MethodsThe Temprano randomized trial was conducted in Abidjan to assess the effectiveness of early ART and Isoniazid (INH) prophylaxis for tuberculosis in HIV-infected persons with high CD4 counts below 800 cells/mm3 without any indication for starting ART. Patients initiating early ART before December 2010 were included in this sub-study. BMI was categorized as: underweight (<18.5 kg/m2), normal weight (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2) and obese (≥30 kg/m2). At baseline and after 24 months of ART, prevalence of being overweight or obese and factors associated with being overweight or obese were estimated using univariate and multivariate logistic regression.ResultsAt baseline, 755 participants (78 % women; median CD4 count 442/mm3, median baseline BMI 22 kg/m2) initiated ART. Among them, 19.7 % were overweight, and 7.2 % were obese at baseline. Factors associated with being overweight or obese were: female sex aOR 2.3 (95 % CI 1.4–3.7), age, aOR for 5 years 1.01 (95 % CI 1.0–1.2), high living conditions aOR 2.6 (95 % CI 1.5–4.4), High blood pressure aOR 4.3 (95 % CI 2.0–9.2), WHO stage 2vs1 aOR 0.7 (95 % CI 0.4–1.0) and Hemoglobin ≥95 g/dl aOR 3.0 (95 % CI 1.6–5.8). Among the 597 patients who attended the M24 visit, being overweight or obese increased from 20.4 to 24.8 % (p = 0.01) and 7.2 to 9.2 % (p = 0.03) respectively and factor associated with being overweight or obese was immunological response measured as an increase of CD4 cell count between M0–M24 (for +50 cells/mm3: aOR 1.01; 95 % CI 1.05–1.13, p = 0.01).ConclusionThe weight categories overweight and obese are highly prevalent in HIV-infected persons with high CD4 cell counts at baseline, and increased over 24 months on ART in this Sub-Saharan African population.

Clinical Correlates and Drug Resistance in HIV-Infected and -Uninfected Pulmonary Tuberculosis Patients in South India.

ObjectivesTo examine demographics, clinical correlates, sputum AFB (acid fast bacilli) smear grading DOTS (Directly Observed Therapy Short Course) uptake, and drug resistance in a cohort of newly-diagnosed, smear positive pulmonary tuberculosis (TB) patients with respect to HIV status at baseline, and compare smear conversion rates, side effects and mortality after two months.DesignA prospective study among 54 HIV positive and 41 HIV negative pulmonary TB patients. Data were collected via face-to-face interviews, review of medical records, and lab tests.ResultsHIVTB co-infected patients, though more symptomatic at baseline, showed more improvement in their symptoms compared to HIV-uninfected TB patients at follow-up. The HIV co-infected group had more prevalent perceived side effects, and sputum smear positivity was marginally higher compared to the HIV negative group at follow-up. Mortality was higher among the HIV-infected group. Both groups had high rates of resistance to first-line anti-tubercular drugs, particularly isoniazid. There was no significant difference in the drug resistance patterns between the groups.ConclusionsPrompt initiation and provision of daily regimens of ATT (Anti-Tubercular treatment) along with ART (Anti-Retroviral treatment) via ART centers is urgently needed in India. As resistance to ART and/or ATT is directly linked to medication non-adherence, the use of counseling, regular reinforcement, early detection and appropriate intervention strategies to tackle this complex issue could help prevent premature mortality and development of resistance in HIV-TB co-infected patients. The high rate of isoniazid resistance might preclude its use in India as prophylaxis for latent TB in HIV infected persons as per the World Health Organization (WHO) guideline.

Tuberculosis in HIV-infected persons in British Columbia during the HAART era.

Prior to the introduction of highly active antiretroviral therapy (HAART), active tuberculosis (TB) was a major contributor to HIV-related morbidity and mortality in Canada and other low-incidence regions. We performed this study to examine TB incidence, clinical manifestations and screening uptake in HIV-infected TB patients during the era of HAART therapy. We performed a retrospective study on all HIV-infected TB patients in British Columbia over a 10-year period (2003-2012). Demographic and clinical characteristics were extracted along with screening and treatment outcomes. Trends in provincial TB incidence, HIV testing and HAART prevalence were also examined. In total, 2,839 TB cases were identified in BC during this period, including 129 HIV-infected TB patients. Surprisingly, only 64 HIV-infected TB patients (50%) had a documented screening tuberculin skin test (TST) prior to TB diagnosis. Of the 39 HIV-infected TB patients with prior TST positivity, 38 (97.4%) had not completed a course of isoniazid preventive therapy. TB incidence decreased significantly in the HIV-infected population of BC over the study period, from 1.9 to 0.5 TB cases per 1,000 HIV-infected individuals (p<0.001). The incidence of HIV-TB decreased significantly over the past decade despite suboptimal latent TB infection screening and prevention practices. This decrease in TB incidence is likely attributable to the increased uptake of HAART. Consideration should be given to intensifying prevention efforts to accelerate TB elimination in HIV-infected populations in low-incidence regions.

Factors associated with unfavorable evolution of tuberculosis in HIV infected persons

Methods We performed an observational, retrospective study (01 January 2009 – 31 December 2011) on 387 HIV-infected patients in evidence at the HIV/AIDS Craiova Regional Center. We analyzed the epidemiological, clinical and paraclinical data (smears and cultures for Mycobacterium tuberculosis, immunovirological evaluation) for patients who presented at least 2 times per year at the regional center.

Incidence of and risk factors for active tuberculosis in human immunodeficiency virus-infected patients in South Korea

In South Korea, a high-income country with an intermediate tuberculosis (TB) burden and low human immunodeficiency virus (HIV) prevalence, studies on incidence and risk factors of TB in HIV-infected persons have rarely been reported. To investigate the incidence of and risk factors for active TB in HIV-infected persons in South Korea. A retrospective analysis was conducted of 1265 HIV-1 infected patients who visited four hospitals in South Korea between 1985 and 2012. We analysed the incidence of TB during the follow-up period. To investigate risk factors associated with active TB, we conducted a 1:2 matched case-control study of HIV-infected patients with newly active TB and controls without active TB who had similar CD4(+) T-cell counts and dates of first visit. Over a total of 4457 person-years (py), 185 (14.6%) subjects were diagnosed with active TB; the incidence was 4.2 cases/100 py. In multivariate analysis, low body mass index (P = 0.033) and current smoking (P = 0.003) were independent risk factors for TB in HIV-infected patients. Further strategies on prevention and treatment of active TB among HIV-infected patients should be implemented in South Korea. Encouraging smoking cessation and supporting good nutrition may be ways to reduce the incidence of active TB in HIV-infected patients.

Efficacy of a Six-Month versus a 36-Month Regimen for Prevention of Tuberculosis in HIV-Infected Persons in India: A Randomized Clinical Trial

BackgroundThe optimal duration of preventive therapy for tuberculosis (TB) among HIV-infected persons in TB-endemic countries is unknown.MethodsAn open-label randomized clinical trial was performed and analyzed for equivalence. Seven hundred and twelve HIV-infected, ART-naïve patients without active TB were randomized to receive either ethambutol 800 mg and isoniazid 300 mg daily for six-months (6EH) or isoniazid 300 mg daily for 36-months (36H). Drugs were dispensed fortnightly and adherence checked by home visits. Patients had chest radiograph, sputum smear and culture performed every six months, in addition to investigations if they developed symptoms. The primary endpoint was incident TB while secondary endpoints were all-cause mortality and adverse events. Survival analysis was performed on the modified intent to treat population (m-ITT) and rates compared.FindingsTuberculosis developed in 22 (6.4%) of 344 subjects in the 6EH arm and 13 (3.8%) of 339 subjects in the 36H arm with incidence rates of 2.4/100py (95%CI- 1.4–3.5) and 1.6/100py (95% CI-0.8–3.0) with an adjusted rate ratio (aIRR) of 1.6 (0.8–3.2). Among TST-positive subjects, the aIRR of 6EH was 1.7 (0.6–4.3) compared to 36H, p = 0.8. All-cause mortality and toxicity were similar in the two arms. Among 15 patients with confirmed TB, 4 isolates were resistant to isoniazid and 2 were multidrug-resistant.InterpretationBoth regimens were similarly effective in preventing TB, when compared to historical incidence rates. However, there was a trend to lower TB incidence with 36H. There was no increase in isoniazid resistance compared to the expected rate in HIV-infected patients.The trial is registered at ClinicalTrials.gov, NCT00351702.

Positive predictive value of Interferon-gamma release assay for incident active tuberculosis in HIV-infected persons

Tuberculosis (TB) is the leading cause of death in HIV/AIDS. The incidence of active TB is 30 times higher in HIV-infected persons. Treatment of latent TB infection (LTBI) is pivotal to the control of TB. We aim to determine the positive predictive value of an interferon-gamma release assay, QuantiFERON-TB GOLD test (QFT), for incident active TB in HIV-infected persons.

Human Immunodeficiency Virus-Associated Tuberculosis

Human Immunodeficiency Virus-Associated Tuberculosis

HIV Infection–Related Tuberculosis: Clinical Manifestations and Treatment

Several aspects of human immunodeficiency virus (HIV) infection-related tuberculosis (TB) and its treatment differ from those of TB in HIV-uninfected persons. The risk of TB and the clinical and radiographic manifestations of disease are primary examples. Antiretroviral therapy has a profound effect on lowering the risk of TB in HIV-infected persons, but it can also be associated with immune reconstitution inflammatory disease and unmasking of previously subclinical disease. There are also differences in treatment of HIV infection-related TB because of overlapping drug toxicities and drug-drug interactions between antiretroviral therapy and anti-TB therapy.

HIV Infection and Multidrug‐Resistant Tuberculosis—The Perfect Storm

Multidrug-resistant (MDR) tuberculosis (TB) has emerged as a global epidemic, with ~425,000 new cases estimated to occur annually. The global human immunodeficiency virus (HIV) infection epidemic has caused explosive increases in TB incidence and may be contributing to increases in MDR-TB prevalence. We reviewed published studies and available surveillance data evaluating links between HIV infection and MDR-TB to quantify convergence of these 2 epidemics, evaluate the consequences, and determine essential steps to address these epidemics. Institutional outbreaks of MDR-TB have primarily affected HIV-infected persons. Delayed diagnosis, inadequate initial treatment, and prolonged infectiousness led to extraordinary attack rates and case-fatality rates among HIV-infected persons. Whether this sequence occurs in communities is less clear. MDR-TB appears not to cause infection or disease more readily than drug-susceptible TB in HIV-infected persons. HIV infection may lead to malabsorption of anti-TB drugs and acquired rifamycin resistance. HIV-infected patients with MDR-TB have unacceptably high mortality; both antiretroviral and antimycobacterial treatment are necessary. Simultaneous treatment requires 6-10 different drugs. In HIV-prevalent countries, TB programs struggle with increased caseloads, which increase the risk of acquired MDR-TB. Surveillance data suggest that HIV infection and MDR-TB may converge in several countries. Institutional outbreaks, overwhelmed public health programs, and complex clinical management issues may contribute to the convergence of the MDR-TB and HIV infection epidemics. To forestall disastrous consequences, infection control, rapid case detection, effective treatment, and expanded program capacity are needed urgently.

Effect of Routine Isoniazid Preventive Therapy on Tuberculosis Incidence Among HIV-Infected Men in South Africa

Tuberculosis preventive therapy reduces tuberculosis incidence among human immunodeficiency virus (HIV)-infected individuals in clinical trials, but implementation has been limited and there are no data on effectiveness under routine conditions. To determine the effect on tuberculosis incidence of a clinic providing isoniazid preventive therapy to HIV-infected adults under routine conditions. Randomized intervention study with a novel incremental recruitment design. Between 1999 and 2001 (before antiretroviral therapy was available), 1655 HIV-infected male employees of a South African gold-mining company (median age, 37 years) were enrolled in the study. Median follow-up was 22.1 months. Employees were invited in random sequence to attend a workplace HIV clinic. Isoniazid, 300 mg/d, was self-administered for 6 months among attendees with no evidence of active tuberculosis. Incidence of tuberculosis (including both first and recurrent episodes) during the periods before and after clinic enrollment. A total of 1016 of 1655 men included in the analysis attended the clinic at least once. Six hundred seventy-nine (97%) of 702 men eligible to start primary isoniazid preventive therapy did so. The tuberculosis incidence rate before vs after clinic enrollment was 11.9 vs 9.0 per 100 person-years, respectively (incidence rate ratio [IRR] after adjustment for calendar period, 0.68; 95% confidence interval [CI], 0.48-0.96). In a multivariable analysis adjusting for calendar period, age, and silicosis grade, the tuberculosis IRR for clinic enrollment was 0.62 (95% CI, 0.43-0.89). In a further analysis excluding individuals with a history of tuberculosis (and, hence, ineligible for isoniazid preventive therapy), the adjusted IRR for clinic enrollment was 0.54 (95% CI, 0.35-0.83). Enrollment in a clinic offering primary isoniazid preventive therapy to HIV-infected adults reduced tuberculosis incidence by 38% overall and by 46% among individuals with no history of tuberculosis prior to the study. Tuberculosis incidence remained high despite isoniazid preventive therapy, and further work is needed to determine how to use additional interventions most effectively to reduce morbidity and mortality due to tuberculosis in HIV-infected persons.

Treatment of tuberculosis in HIV infected persons in the era of highly active antiretroviral therapy,

Treatment of tuberculosis in HIV infected persons in the era of highly active antiretroviral therapy,

Treatment of tuberculosis in HIV-infected persons in the era of highly active antiretroviral therapy.

To assess the risks and benefits of administering highly active antiretroviral therapy (HAART) during the treatment of tuberculosis (TB) in HIV-infected patients. HIV-1 patients presenting to 12 HIV centres in Greater London and south-east England with culture-proven TB were identified from January 1996 to June 1999. Case-notes were reviewed retrospectively. Patients (n = 188) were severely immunocompromised with a median CD4 cell count at TB diagnosis of 90 x 106 cells/l (IQR: 30-180). At presentation, 85% (n = 159) were not taking antiretrovirals. A total of 45% commenced HAART during TB treatment, which was associated with significant reductions in viral load, AIDS-defining illness (ADI) [3.5 versus 24.5%; relative risk (RR) = 0.14] and mortality. Only nine of 91 (10%) patients with a CD4 count > 100 x 106 cells/l at TB diagnosis experienced a further ADI, whereas 18 of 92 (20%) patients with a CD4 count < 100 x 106 cells/l developed this complication. Adverse events (AE) occurred in 99 (54%) of 183 patients, one-third of whom changed or interrupted HIV and/or TB medication. The majority of AE occurred within the first 2 months, with peripheral neuropathy (21%), rash (17%) and gastrointestinal upset (10%) occurring most commonly. Many physicians delay HAART in patients presenting with TB because of pill burden, drug/drug interactions and toxicity. Although the use of HAART led to significant reductions in viral load, ADI and mortality, co-infected patients commonly experienced AE leading to interruptions in TB/HIV therapy. We therefore recommend starting HAART early for patients with advanced HIV disease (CD4 < 100 x 106 cells/l) and deferring HAART until the continuation phase of TB therapy (i.e. after 2 months) for patients who are clinically stable (CD4 > 100 x 106 cells/l).