Tuberculosis

An open-labeled, randomized, controlled trial of 642 patients with HIV/TB co-infection in South Africa from 2005 to 2008 found that starting ART during TB therapy reduced mortality by 56%. Four hundred and twenty-nine patients started ART within eight weeks of starting TB therapy while 213 patients started ART after completing TB therapy, which was, on average, 190 days later than the group starting ART during TB therapy. The group starting ART during TB therapy had a death rate of 5.4 per 100 person-years, which was significantly lower than the death rate of 12.1 per 100 person-years among the group starting ART after TB therapy. Among patients with CD4 counts below 200 cells per cubic mm, the rate of death was 46% lower in the group starting ART during TB therapy. The proportion of patients with a suppressed HIV RNA level was significantly higher in the group starting ART during TB therapy. While 12.4% of patients in the group starting ART during TB therapy developed immune reconstitution inflammatory syndrome (IRIS), which was higher than the group starting ART after TB therapy, none of the deaths in the first group were due to IRIS. Approximately half of the study participants were women, yet sex-disaggregated data was not analyzed. 

A study in Ethiopia that assessed the effect of HAART on patient mortality and TB incidence rates under routine clinical care conditions in 2003 found that HAART resulted in a 65% decline in mortality and the TB incidence rate was lower in the HAART group. HAART improved survival and decreased TB incidence to a level similar to that achieved in developed countries during the early years of HAART. In August 2003, the hospital started providing HAART to patients. All HIV-positive patients who visited the clinic since January 2003 were followed and treated for opportunistic infections. Patients who were followed from January 2003 to August 2003 were the “pre-HAART cohort” and patients followed from August 2003 to August 2005 were the “HAART cohort.” The last day of pre-HAART followed was April 1, 2004. After April 1, 2004 all patients of this hospital who met the Ethiopian HAART treatment guidelines had access to HAART at this hospital. Pre-HAART patients who joined the HAART group contributed person-time to both cohorts at different periods. A cohort of 90 men and 95 women, or a total of 185 patients were followed prior to accessing HAART. A cohort of 102 men and 78 women, for a total cohort of 180 patients were followed in the HAART cohort. At the end of the pre-HAART period, 10 patients (5.4%) were lost to follow-up; 8 (4.3%) were transferred to another health institution; 47 (25.4%) died and 120 (64.9%) were under regular follow-up. The pre-HAAART mortality rate was 58.1 per 100 person-years of observation. TB incidence rate with HAART was reduced by almost 90%. Community agents visited patients on a monthly basis in the patient’s home. Community agents received training and had completed secondary school. Community agents reported the patient’s status to the hospital following each visit to the patient’s home.

A retrospective, observational study of 667 co-infected with HIV and TB patients in Thailand from 2005-2006 found that patients that did not use ART during TB treatment had five times the risk of dying than those that did use ART. The use of ART during TB treatment was the single most important predictor of survival. The risk of death increased the longer that ART was delayed during TB treatment among 126 patients that started ART after TB diagnosis. Risk was reduced for patients starting ART treatment early while using fluconazole. The use of efavirenz- or nevirapine-containing ART was also found to decrease the risk of death when compared with no ART use.

An observational study of 68 patients attending a community-based ART clinic in South Africa found that initiating ART among patients with undiagnosed TB was not associated with adverse outcomes. Twenty-three (34%) patients started ART after receiving a smear-negative TB diagnosis and before TB diagnosis and TB treatment. The remaining 45 patients (66%) started TB treatment before starting ART. Of the 23 patients starting ART before starting TB treatment, 26% had sudden onset of TB during the first few weeks of ART treatment but none of them developed immune reconstitution inflammatory syndrome (IRIS). Of the 45 patients starting TB treatment before starting ART treatment, 11% developed immune reconstitution inflammatory syndrome (IRIS). The majority of patients were women (73.5%), yet sex-disaggregated data was not analyzed. Results indicated that starting ART does not need to be delayed until TB diagnosis or TB treatment begins. Inadvertent initiation of ART among patients with unrecognized prevalent TB was not associated with adverse consequences.  Therefore, “it is not necessary to wait for cultures to be reported prior to starting ART” (Kerkhoff et al., 2011: 1004). 

A retrospective cohort study of 195 patients with XDR TB in South Africa from 2002 to 2008 found that HAART significantly reduced the number of deaths among HIV-positive patients co-infected with XDR TB. Forty-seven percent of study participants were HIV-positive, of whom 63% were taking HAART. Of the HIV-positive patients who died, a greater number were not taking HAART (66%) compared to those taking HAART (25%). Patients taking HAART had a lower CD4 cell count (average 267 per mm3) than those not taking HAART (average 440 per mm3). Results indicate that treatment with HAART should be used at an early stage of HIV infection among patients co-infected with XDR TB. Drug resistance did not differ by HIV status. Twenty-one patients died before starting treatment for XDR TB; cause of death was unknown. Approximately half of the study population was women, yet it is unknown how many of those women were living with HIV.

A retrospective cohort study of 1,003 patients, 411 of which received HAART and 592 of which did not, between January 2000 and December 2004 in Thailand found that those who did not receive HAART were 20 times more likely to die compared with those on HAART. Within the HAART group, those who delayed HAART initiation after 6 months had a higher mortality rate than those who initiated within 6 months of TB diagnosis. The average CD4 count was 53 when initiating HAART. Among those on HAART the survival rate after TB diagnosis was 96.1% after one year on HAART, 94.0%, after two years on HAART, and 87.7% after three years on HAART. Among those not on HAART, survival was 44.4% after one year; 19.2% after two years; and 9.3% after three years. Those infected with drug-resistant TB were twice as likely to die as compared with those with drug-susceptible TB.

From February 2003 through January 2004, 2,342 patients were registered for TB treatment in Ubon-ratchathani, Thailand. Of these, 225 (10%) were confirmed as HIV-positive prior to their TB diagnosis, and of the remaining 2,117 patients, 680 agreed to be tested for HIV, and 104/680 (15%) were found to be HIV-positive.  The 329 (14%) TB patients with confirmed HIV diagnoses were followed prospectively to assess the impact of HAART on TB treatment outcomes. Among the 290 TB patients with known outcomes, 71 were on HAART and 219 were not.  Death during TB treatment occurred in 7% (5 of 71) on HAART and 43% (94 of the 219) not on HAART. Antiretroviral therapy was associated with a significant reduction in deaths among those on HAART prior to initiating TB treatment.

A multi-center cohort study in Spain of 2,238 HIV-seroconverters compared TB incidence in pre-HAART and HAART eras and found that the risk of developing TB was 70% lower in the HAART era than in the pre-HAART era.

A number of randomized controlled trials have shown that isoniazid preventive therapy reduces the incidence of active TB disease in people living with HIV.

A Cochrane review of 12 randomized controlled trials from 1993 - 2007 with 8,578 HIV positive patients co-infected with inactive TB, found that any anti-TB drug reduced the risk of developing active TB by 32% when compared with placebo. Patients were randomly assigned to TB preventative therapy or placebo, or to alternative TB preventative therapy. Risk was further reduced by 62% among patients with a positive TB skin test. Preventative therapy led to an increase in adverse events, which increased the likelihood of stopping treatment among patients on combination therapies. Approximately 47% of patients were women. Sex disaggregated data was not analyzed.

A randomized, double-blind, placebo-controlled trial of 1,995 adults living with HIV in Botswana from 2004–2009 found that 36 months of isoniazid preventative treatment reduced the incidence of tuberculosis by 43% when compared to six months of isoniazid preventative treatment. The benefit of continuous therapy was even higher for patients with a positive tuberculin skin test with a 74% reduction in TB incidence. Seventy-two percent of participants were women, 69% had CD4 counts of 200 cells/cubic mm or more, and 73% had a negative tuberculin skin test. All participants received at least six months of isoniazid preventative treatment; the control group received a placebo for the remaining 30 months while the intervention group continued to receive isoniazid preventative treatment for a total of 36 months. Incidence of TB was significantly higher in the six-month only group at 1.26% compared to 0.72% in the 36-month treatment group. Among participants with a positive skin test, 6% of the six-month only group developed TB compared to 1.6% of the 36-month treatment group. Those with a positive skin test that received only six months of treatment were three times more likely to develop TB than those on continuous treatment. There was no significant benefit of continuous treatment for participants with a negative tuberculin skin test. Participants with CD4 counts of 200 cells/cubic mm or more benefited more from continuous treatment than those with CD4 counts of 200 cells/cubic mm or less. Starting antiretroviral therapy at the start of the study also had protective effects with the highest TB incidence occurring in participants not on ART; use of ART reduced TB incidence by 50%.

A sub-cohort study, nested within a randomized trial, of 558 patients living with HIV who had a positive tuberculin-skin-test result but did not have active TB in Tanzania from 2001 to 2008 found that patients completing six months of isoniazid preventative therapy had higher survival rates than patients not completing therapy. The mortality rate among patients completing therapy was 60% lower than that of patients not completing therapy; 488 patients completed six months of isoniazid preventative therapy compared to 70 that did not. The majority of study patients were female (70%) and most patients had a CD4 count less than or equal to 350 cells/cubic mm (29%). Although there was no difference in the number of new active TB infections between the two groups, there was a significant association between completing six months of isoniazid preventative therapy and increased survival.

A retrospective analysis evaluated the impact of isoniazid preventative therapy on mortality of 3,258 HIV-positive miners in South Africa who initiated isoniazid preventative therapy and found that the mortality rate was significantly lower, with a 53% reduction in mortality among those on isoniazid preventative therapy than among those who did not receive isoniazid preventative therapy.

A retrospective medical record review of 11,026 HIV-positive patients who were accessing medical care at 29 public clinics in Rio de Janeiro, Brazil from September 2003 until September 2005 found that isoniazid preventive therapy offered in conjunction with expanded access to HAART may improve TB control among people with HIV in high burden settings. The study was conducted to determine the rates of TB in patients who received no HAART or isoniazid preventative therapy; only HAART; only IPT; or both HAART and isoniazid preventative therapy. The overall incidence rate of TB incidence was 2.28 cases/100 person-years. Among the patients who received no HAART or isoniazid preventative therapy incidence was 4.01 cases/100 person years. Patients who received HAART alone had incidence of 1.90 cases/100 person years, and those receiving isoniazid preventative therapy along had a rate of 1.27 cases/100 person years.  The TB incidence among patients receiving both isoniazid preventative therapy and HAART was 0.8 cases/100 person years, with a 76% reduction in risk for developing TB in this group.

An observational cohort study of 3,270 HIV-positive employees at an HIV workplace program, in a setting with high TB incidence, in South Africa from 2004 to 2007 examining the association of isoniazid preventative therapy and mortality of employees starting ART found that mortality rates were lower among employees receiving isoniazid preventative therapy before or with ART than employees not receiving isoniazid preventative therapy, after controlling for confounders. The use of isoniazid preventative therapy had a higher protective effect among employees with CD4 cell counts less than 50 cells/cubic mm when compared to employees with CD4 cell counts above 50 cells/cubic mm. Employees were followed from the start of ART to death, leaving employment, or 12 months from ART start date. All employees were screened annually for TB, regardless of HIV status, and those with TB were treated on short-dose rifampicin-based therapy. Information about past medical history, use of drug therapies, CD4 count, and TB symptoms were recorded for all employees in the HIV workplace program. For employees using ART, death rates were recorded as well. Of the 3,270 employees enrolled in the study, 28% started isoniazid preventative therapy before or during the first three months of starting ART, 96% of those starting within the first week, and 40.9% started cotrimoxazole before or during ART. A small percentage of enrolled employees had TB before starting ART (7.2%). Employees started on isoniazid preventative therapy tended to have higher CD4 cell counts, lower viral load, and higher hemoglobin levels. Approximately 7% were women, however, sex disaggregated data was not analyzed. “Although the results of randomized trials of IPT are awaited, our data support the routine use of IPT in HIV care programmes in line with WHO recommendations” (Charalambous et al., 2010: S12).

A prospective observational cohort study of 240 HIV patients in South Africa using an intensive TB pretreatment screening tool found that among patients newly starting ART, 36% had TB and the screening tool resulted in a two-fold decrease in incidence in the first four months of ART. The study compared prevalent TB rates to incident TB rates. Prevalent TB was defined as being diagnosed between the time of study enrollment and ART initiation, typically 28 days. Incident TB was defined as having both TB symptoms and diagnosis occur after starting ART. Of the 87 patients diagnosed with TB, 89% had pulmonary involvement. Also, 87% were prevalent TB and 13% were incident TB, with a baseline prevalence rate of 31.5%. The majority of patients were women (72%), of which 14% were pregnant. The average CD4 cell count at baseline was 125 cells/μl and 54% of patients had WHO stage 3 or 4 disease. Results suggest that many incident cases of TB can be detected as prevalent TB cases when patients start ART if routine screening with a sensitive diagnostic test is used.

Instituting a large component of village outreach work in Lesotho resulted in increased numbers of TB patients diagnosed and treated in the context of scale up of HIV treatment. Lesotho has the third highest prevalence of HIV and the fourth highest prevalence of TB worldwide and the majority of TB patients are co-infected with HIV. Instituting an antiretroviral therapy program in a health center in a mountainous region of Lesotho resulted in a 10-fold increased in the detection of TB among patients with and without HIV.  The study used a retrospective review of the clinical register during 2006, with data drawn from the cohort of patients who were diagnosed with TB before the implementation of the HIV program, from Jan. 1 to June 30, 2006 and those who were diagnosed with TB after the implementation of the HIV program from July 1-Dec. 31, 2006. With the initiation of ART, all patients were actively screened for both HIV and TB. Prior to the initiation of the ART program, only nine cases of TB were diagnosed, of whom three were women; after the ART program was started, 102 patients were diagnosed with TB, of whom 59 were women. Factors leading to the increase in diagnosing TB included a more comprehensive TB diagnostic algorithm, a greater number of health personnel in the health center, and “a large component of village outreach work.”

From the latter part of 2001 to December 2004, in the Thyolo District in Malawi, TB/HIV community volunteers screened for TB symptoms. One in five individuals referred for TB testing was smear-positive. Households where a volunteer found chronic cough had an annual TB incidence rate eight times higher than the general population.

 A total of 18,329 individuals received HIV counseling and testing in six districts in Tamil Nadu, India in 2007. Of these 1,065 were identified as TB suspects by HIV test counselors and were referred to TB microscopy centers for diagnosis based on symptoms suggestive of TB history (i.e. cough of 3 or more weeks).  Of those referred, 83% (or 888 individuals) followed up on the referrals, and 12% were found to be sputum smear-positive.

A cluster-randomized trial of 1,455 HIV-positive patients co-infected with TB in Rio de Janeiro, Brazil, from 2005–2010, assessed the impact of routine screening and treatment of TB in HIV patients and found that 85% of patients completed isoniazid preventative therapy. Only 20% reported adverse events, which lead to early discontinuation of treatment. Patients receiving HAART were more likely to complete isoniazid preventative therapy than patients not receiving HAART. On average, patients completing isoniazid preventive therapy had a significantly higher CD4 cell count (527 cells/cubic mm) at baseline than those not completing therapy (491 cells/cubic mm). Completion rates were similar among men (85%) and women (84%). The study was conducted in 29 public primary care clinics that offered universal access to ARVs to all HIV-positive patients, which is Brazilian national policy. Clinics were randomly assigned a date to start screening patients for TB and providing isoniazid preventive therapy. Clinic healthcare workers were trained on TB and HIV screening methods, disease prevention measures, reading tuberculin skin tests correctly, and pre- and post-test counseling for infected patients. Six field supervisors were hired to support the clinics and conduct real-time evaluation measures. The supervisors also developed a strategy to help physicians remember the dates when patients should be screened for latent TB infection. Study staff created and distributed educational materials to support the implementation of isoniazid preventive therapy. Advocacy activities were conducted at the local level to educate and encourage TB-HIV integration and at the national level to increase the scale-up of isoniazid preventive therapy and TB/HIV collaboration. To collect additional data, medical records of all HIV-positive patients attending the 29 clinics were reviewed. Three years after the start of the study 80% of patients had received a tuberculin skin test with an average time of 44 weeks between a patient’s first clinic visit and being tested for TB. For eligible patients, isoniazid preventive therapy was started, on average, 8.9 weeks after diagnosis.

A cross-sectional study evaluating the national scale-up in TB/HIV integration services in 23 of the 161 TB clinics in Rwanda from 2005–2009 among 207 patients and 40 staff found that scale-up led to 97% of TB patients knowing their HIV status, an increase in the number of patients accessing HIV treatment and care, and a decrease in the risk of death due to TB/HIV co-infection. The first 10 patients and 1-2 staff at each clinic were interviewed to determine openness to HIV testing, knowledge of TB/HIV, and access to treatment. Of the patients interviewed, 158 (76%) were offered an HIV test at the time of TB diagnosis, 99% of whom accepted and received results. Of the patients who were not offered an HIV test, 80% stated they would take an HIV test if it was offered. The most common reasons for refusing an HIV test was not believing themselves to be at risk for HIV or fear of positive test results. Of staff interviewed, 35% knew that TB was the leading cause of death among people living with HIV and 32% reported offering HIV tests to all TB patients. The most common barriers to offering HIV tests were not enough trained staff or space and patient concern about stigma of test. In addition to interviews, researchers looked at patient records to examine treatment outcomes and testing rates. At baseline 542 patients were receiving TB treatment at the 23 clinics; 39% of patients were women and 44% were HIV-positive. Among the HIV-positive TB patients 2.5% were taking co-trimoxazole and 12.3% had started ART. Following the scale-up of TB/HIV integration services the number of TB patients that had an HIV test increased from 48% to 97%, TB/HIV patients on cotrimoxazole increased from 2.5% to 92%, and the number of TB/HIV co-infected patients on ART increased from 12.5% to 49%. The risk of death among TB patients decreased as well.

Integration in six sub-Saharan African countries of a five symptom questionnaire asking about cough, fever, weight loss, night sweats in routine HIV care resulted in 64% of 32,731 people screened, with 22% screening positive for TB of whom an average of 12% received a diagnosis of TB and initiated treatment.

A cross sectional study in 2007 in two districts in India with 568 TB patients, 80% reported being referred for HIV testing after presenting for TB treatment. Of the 568 TB patients, 33% were women. Of the 568 TB patients, 13% reported that they had been tested for HIV prior to receiving a diagnosis of TB. Of the 495 TB patients referred for VCT, 97% reported they had HIV testing and counseling and collected their HIV test results.

A case-study examining the feasibility of integrating TB and HIV care for all patients attending the Gisenyi District Hospital in Rwanda found that provider-initiated HIV testing and counseling (PITC) of TB patients increased the detection of TB and increased the number of TB patients with known HIV status. The introduction of a TB screening survey increased the detection of TB in hospitalized patients and those in outpatient settings. The number of TB patients with known HIV status increased from 82% in 2004, before the start of the program, to 97% in 2006, one year after the start of the program. Of newly diagnosed HIV patients, approximately 75% started cotrimoxazole preventive treatment and about 50% started ART. Provider-initiated HIV testing and counseling (PITC) of TB patients used mainly on-site resources, which increased the ease and decreased the cost of starting a new program. Of note, the only additional resource was the hiring of a new TB-HIV focal point person who supervised and promoted collaboration between staff and integration of services.

A cross-sectional study in 2009 in South Africa with 290 men and 310 women found that having received TB and HIV information from primary health care facilities was the leading predictor of uptake of HIV testing. Unmarried patients who had received TB/HIV information at TB clinics were more than five times as likely to have been tested for HIV as unmarried patients who had not received such information. Even after controlling for confounding factors, having received information on the link between TB and HIV at the primary health care facility emerged as the strongest predictor of self-reported HIV testing. Female TB patients were more likely to have tested for HIV than men. 

A pilot study of 2,795 TB patients in China in 2007 assessing the prevalence of TB-HIV co-infection and the effect of provider-initiated HIV testing and counseling (PITC) found that the acceptance rate for HIV testing was 99.1% and 2.2% of TB patients were co-infected with HIV. Of the sixty TB patients diagnosed with HIV, 55 were newly diagnosed; the remaining five had been diagnosed before the study began. Thirty percent of the TB patients were women, who had similar acceptance rate of HIV testing (98.6%) when compared to men (99.3%). HIV prevalence was significantly higher among men (2.6%) than among women (1.1%).

A study evaluated the uptake of provider-initiated HIV counseling and testing among TB patients in three care settings in Kinshasa, Democratic Republic of Congo. All patients registered for TB care at three TB clinics between August 2004 and June 2005, were either offered HIV counseling and testing at either the TB clinic, the primary health center to which the TB clinic belonged or were referred to a free-standing VCT center. Between 95-98% of TB patients were HIV tested when the counseling and testing was performed at the TB clinic or primary health center. However, only 68.5% of TB patients who were referred to VCT center followed up on the referral.

A pilot cross-referral initiative instituted between VCT centers and treatment facilities of the Revised National TB Control Programme in four districts of Maharashtra, India found significant numbers of active TB cases among VCT patients and HIV co-infection in TB patients. From 2003 to 2004, 336 or 3% of 9,921 VCT patients were diagnosed with TB. Of the 765 TB cases, 181 or 24% were found to be HIV-positive, representing 11% of the newly detected people living with HIV in the four districts. All VCTs were located in the same facility as a microscopy center that diagnosed TB. A two-day training on TB-HIV and cross-referral was held for VCT counselors and TB treatment supervisors. Quarterly regional review meetings with VCT and TB staff were held to monitor progress and solve problems in cross-referral. VCT included those who came for the first time to a VCT center as well as those who come for further counseling after learning their HIV status. Patients at VCT centers who had a cough for more than three weeks were referred for the standard sputum exam for TB. Persons with symptoms of TB, such as fever or weight loss, were referred to a medical officer, with referrals made irrespective of HIV status. TB patients who reported multiple sexual partners and/or STIs were referred to VCT. HIV status of individuals referred was not included in registers to maintain confidentiality. Similar VCT and TB service linkages were established across 14 states in India, with a population of 633 million. In 2006, nearly 60,000 VCT patients were referred for a TB evaluation and 51,000 TB patients were referred to VCT for HIV counseling and testing.

At two PMTCT program clinics in Soweto, South Africa, 370 pregnant women living with HIV were screened for TB symptoms by lay counselors during post-test counseling sessions. Eight women were found to have previously undiagnosed, smear-negative TB disease. Active screening for TB symptoms is feasible.

Clients accessing antenatal clients, TB patients, and medical providers from five health facilities in Kasungu District, Malawi were interviewed to assess the acceptability of TB screening and TB treatment. Most clients found screening acceptable but expressed concern about HIV stigma. All of the service providers agreed that TB screening was important but expressed concern about the increased workload.

Pregnant HIV-positive women who have active TB are at higher risk for mortality. “There is a strong evidence base for screening pregnant HIV-infected women for TB as part of antenatal care. Intensified case finding for TB can reduce morbidity and mortality and prevent transmission of TB in families, the community, and health care settings. Delaying the diagnosis of active TB significantly increases the proportion of infected contacts” (DeLuca et al., 2009: 197). “Although there is a wealth of evidence suggesting that screening for active TB during routine antenatal care would be a beneficial intervention, especially in places with efficient PMTCT program, no country programs have implemented this strategy as part of best practices” (DeLuca et al., 2009: 198).

A descriptive study of 10,070 newly registered TB cases and 755 recurrent TB cases among people living with HIV between 2002 and 2009 in Thyolo District, Malawi found that 80% ART coverage led to a decrease in new TB cases by 33% from 2005 to 2009 and a decrease in recurrent TB cases by 25% from 2006 to 2009. ART scale-up prevented an estimated 1,164 new TB cases and 78 recurrent TB cases from 2005 to 2009. ART access reached 80% in 2007 and remained at that rate in the years following. All HIV-positive patients with WHO Clinical Stage 3 or 4, or a CD4 count of less than 250 cells/mm3 were eligible for ART. HIV/AIDS care and ART were provided free of charge, but isoniazid preventative therapy was not used as a TB treatment strategy in this study. Population data analyzing TB case notification and ART coverage was used to determine the annual association between the number of people on ART and the number of case notifications for new and recurrent TB. From 2005 to 2009 there was a significant decrease in new TB notifications from 259 to 173 cases/100,000 people, which was a 33% reduction. From 2006 to 2009 there was a significant decrease in recurrent TB notifications from 20 to 15 cases/100,000 people, which was a 25% reduction. As the number of people on ART increased the number of new and recurrent TB case notifications decreased significantly.

A retrospective descriptive study using mortality records in two major cities in Zimbabwe, Harare and Bulawayo found that ART scale up averted premature deaths. ART facilities for the public sector opened in 2004. ART coverage by Dec. 2009 was 56% of those meeting the guidelines for Zimbabwe, which was CD4 counts under 200. Death records were analyzed from 1979 to 2998. From 2004 to 2005, provider-initiated testing and counseling for HIV was introduced at health facilities, particularly for patients with suspected or confirmed TB. TB specific mortality increased 18 fold in Bulwayo and 25 fold in Harare. Mortality from TB per 1,000 population peaked in 2002 at 3.5 and declined starting in 2004 with the advent of ART scale up.