Successful Tuberculosis Treatment Outcomes among HIV/TB Coinfected Patients Down-Referred from a District Hospital to Primary Health Clinics in Rural South Africa

BackgroundHIV and tuberculosis (TB) coinfection remains a major public health threat in sub-Saharan Africa. Integration and decentralization of HIV and TB treatment services are being implemented, but data on outcomes of this strategy are lacking in rural, resource-limited settings. We evaluated TB treatment outcomes in TB/HIV coinfected patients in an integrated and decentralized system in rural KwaZulu-Natal, South Africa.MethodsWe retrospectively studied a cohort of HIV/TB coinfected patients initiating treatment for drug-susceptible TB at a district hospital HIV clinic from January 2012-June 2013. Patients were eligible for down-referral to primary health clinics(PHCs) for TB treatment completion if they met specific clinical criteria. Records were reviewed for patients’ demographic, baseline clinical and laboratory information, past HIV and TB history, and TB treatment outcomes.ResultsOf 657(88.7%) patients, 322(49.0%) were female, 558(84.9%) were new TB cases, and 572(87.1%) had pulmonary TB. After TB treatment initiation, 280(42.6%) were down-referred from the district level HIV clinic to PHCs for treatment completion; 377(57.4%) remained at the district hospital. Retained patients possessed characteristics indicative of more severe disease. In total, 540(82.2%) patients experienced treatment success, 69(10.5%) died, and 46(7.0%) defaulted. Down-referred patients experienced higher treatment success, and lower mortality, but were more likely to default, primarily at the time of transfer to PHC.ConclusionDecentralization of TB treatment to the primary care level is feasible in rural South Africa. Treatment outcomes are favorable when patients are carefully chosen for down-referral. Higher mortality in retained patients reflects increased baseline disease severity while higher default among down-referred patients reflects failed linkage of care. Better linkage mechanisms are needed including improved identification of potential defaulters, increased patient education, active communication between hospitals and PHCs, and tracing of patients lost to follow up. Decentralized and integrated care is successful for carefully selected TB/HIV coinfected patients and should be expanded.     

Gender,Migration and HIV in Rural KwaZulu-Natal,South Africa

Objectives

Research on migration and HIV has largely focused on male migration, often failing to measure HIV risks associated with migration for women. We aimed to establish whether associations between migration and HIV infection differ for women and men, and identify possible mechanisms by which women''s migration contributes to their high infection risk.

Design

Data on socio-demographic characteristics, patterns of migration, sexual behavior and HIV infection status were obtained for a population of 11,677 women aged 15–49 and men aged 15–54, resident members of households within a demographic surveillance area participating in HIV surveillance in 2003–04.

Methods

Logistic regression was conducted to examine whether sex and migration were independently associated with HIV infection in three additive effects models, using measures of recent migration, household presence and migration frequency. Multiplicative effects models were fitted to explore whether the risk of HIV associated with migration differed for males and females. Further modeling and simulations explored whether composition or behavioral differences accounted for observed associations.

Results

Relative to non-migrant males, non-migrant females had higher odds of being HIV-positive (adjusted odds ratio [aOR] = 1.72; 95% confidence interval [1.49–1.99]), but odds were higher for female migrants (aOR = 2.55 [2.07–3.13]). Female migrants also had higher odds of infection relative to female non-migrants (aOR = 1.48 [1.23–1.77]). The association between number of sexual partners over the lifetime and HIV infection was modified by both sex and migrant status: For male non-migrants, each additional partner was associated with 3% higher odds of HIV infection (aOR = 1.03 [1.02–1.05]); for male migrants the association between number of partners and HIV infection was non-significant. Each additional partner increased odds of HIV infection by 22% for female non-migrants (aOR = 1.22 [1.12–1.32]) and 46% for female migrants (aOR = 1.46 [1.25–1.69]).

Conclusions

Higher risk sexual behavior in the context of migration increased women''s likelihood of HIV infection.     

Predictors of Death during Tuberculosis Treatment in TB/HIV Co-Infected Patients in Malaysia

Background

Mortality among TB/HIV co-infected patients is still high particularly in developing countries. This study aimed to determine the predictors of death in TB/HIV co-infected patients during TB treatment.

Methods

We reviewed medical records at the time of TB diagnosis and subsequent follow-up of all newly registered TB patients with HIV co-infection at TB clinics in the Institute of Respiratory Medicine and three public hospitals in the Klang Valley between January 2010 and September 2010. We reviewed these medical records again twelve months after their initial diagnosis to determine treatment outcomes and survival. We analysed using Kaplan-Meier and conducted multivariate Cox proportional hazards analysis to identify predictors of death during TB treatment in TB/HIV co-infected patients.

Results

Of the 227 patients studied, 53 (23.3%) had died at the end of the study with 40% of deaths within two months of TB diagnosis. Survival at 2, 6 and 12 months after initiating TB treatment were 90.7%, 82.8% and 78.8% respectively. After adjusting for other factors, death in TB/HIV co-infected patients was associated with being Malay (aHR 4.48; 95%CI 1.73-11.64), CD4 T-lymphocytes count < 200 cells/µl (aHR 3.89; 95% CI 1.20-12.63), three or more opportunistic infections (aHR 3.61; 95% CI 1.04-12.55), not receiving antiretroviral therapy (aHR 3.21; 95% CI 1.76-5.85) and increase per 10³ total white blood cell count per microliter (aHR 1.12; 95% CI 1.05-1.20)

Conclusion

TB/HIV co-infected patients had a high case fatality rate during TB treatment. Initiation of antiretroviral therapy in these patients can improve survival by restoring immune function and preventing opportunistic infections.     

Outcomes of Multidrug-Resistant Tuberculosis Treatment with Early Initiation of Antiretroviral Therapy for HIV Co-Infected Patients in Lesotho

Background

Although the importance of concurrent treatment for multidrug-resistant tuberculosis (MDR-TB) and HIV co-infection has been increasingly recognized, there have been few studies reporting outcomes of MDR-TB and HIV co-treatment. We report final outcomes of comprehensive, integrated MDR-TB and HIV treatment in Lesotho and examine factors associated with death or treatment failure.

Methods

We reviewed clinical charts of all adult patients who initiated MDR-TB treatment in Lesotho between January 2008 and September 2009. We calculated hazard ratios (HR) and used multivariable Cox proportional hazards regression to identify predictors of poor outcomes.

Results

Of 134 confirmed MDR-TB patients, 83 (62%) were cured or completed treatment, 46 (34%) died, 3 (2%) transferred, 1 (1%) defaulted, and 1 (1%) failed treatment. Treatment outcomes did not differ significantly by HIV status. Among the 94 (70%) patients with HIV co-infection, 53% were already on antiretroviral therapy (ART) before MDR-TB treatment initiation, and 43% started ART a median of 16 days after the start of the MDR-TB regimen. Among HIV co-infected patients who died, those who had not started ART before MDR-TB treatment had a shorter median time to death (80 days vs. 138 days, p = 0.065). In multivariable analysis, predictors of increased hazard of failure or death were low and severely low body mass index (HR 2.75, 95% confidence interval [CI] 1.27–5.93; HR 5.50, 95% CI 2.38–12.69), and a history of working in South Africa (HR 2.37, 95% CI 1.24–4.52).

Conclusions

Favorable outcomes can be achieved in co-infected patients using a community-based treatment model when both MDR-TB and HIV disease are treated concurrently and treatment is initiated promptly.     

Treatment of Cryptococcal Meningitis in KwaZulu-Natal,South Africa

Background

Cryptococcal meningitis (CM) remains a leading cause of death for HIV-infected individuals in sub-Saharan Africa. Improved treatment strategies are needed if individuals are to benefit from the increasing availability of antiretroviral therapy. We investigated the factors associated with mortality in routine care in KwaZulu-Natal, South Africa.

Methodology/Principal Findings

A prospective year long, single-center, consecutive case series of individuals diagnosed with cryptococcal meningitis 190 patients were diagnosed with culture positive cryptococcal meningitis, of whom 186 were included in the study. 52/186 (28.0%) patients died within 14 days of diagnosis and 60/186 (32.3%) had died by day 28. In multivariable cox regression analysis, focal neurology (aHR 11 95%C.I. 3.08–39.3, P<0.001), diastolic blood pressure <60 mmHg (aHR 2.37 95%C.I. 1.11–5.04, P = 0.025), concurrent treatment for tuberculosis (aHR 2.11 95%C.I. 1.02–4.35, P = 0.044) and use of fluconazole monotherapy (aHR 3.69 95% C.I. 1.74–7.85, P<0.001) were associated with increased mortality at 14 and 28 days.

Conclusions

Even in a setting where amphotericin B is available, mortality from cryptococcal meningitis in this setting is high, particularly in the immediate period after diagnosis. This highlights the still unmet need not only for earlier diagnosis of HIV and timely access to treatment of opportunistic infections, but for better treatment strategies of cryptococcal meningitis.     

Incidence of TB and HIV in Prospectively Followed Household Contacts of TB Index Patients in South Africa

Objective

To report the incidence rates of TB and HIV in household contacts of index patients diagnosed with TB.

Design

A prospective cohort study in the Matlosana sub-district of North West Province, South Africa.

Methods

Contacts of index TB patients received TB and HIV testing after counseling at their first household visit and were then followed up a year later, in 2010. TB or HIV diagnoses that occurred during the period were determined.

Results

For 2,377 household contacts, the overall observed TB incidence rate was 1.3 per 100 person years (95% CI 0.9–1.9/100py) and TB incidence for individuals who were HIV-infected and HIV seronegative at baseline was 5.4/100py (95% CI 2.9–9.0/100py) and 0.7/100py (95% CI 0.3–1.4/100py), respectively. The overall HIV incidence rate was 2.2/100py (95% CI 1.3–8.4/100py).

Conclusions

In the year following a household case finding visit when household contacts were tested for TB and HIV, the incidence rate of both active TB and HIV infection was found to be extremely high. Clearly, implementing proven strategies to prevent HIV acquisition and preventing TB transmission and progression to disease remains a priority in settings such as South Africa.     

HIV incidence remains high in KwaZulu-Natal, South Africa: evidence from three districts

Background

HIV prevalence and incidence among sexually active women in peri-urban areas of Ladysmith, Edendale, and Pinetown, KwaZulu-Natal, South Africa, were assessed between October 2007 and February 2010 in preparation for vaginal microbicide trials.

Methodology/Principal Findings

Sexually active women 18–35 years, not known to be HIV-positive or pregnant were tested cross-sectionally to determine HIV and pregnancy prevalence (798 in Ladysmith, 1,084 in Edendale, and 891 in Pinetown). Out of these, approximately 300 confirmed non-pregnant, HIV-negative women were subsequently enrolled at each clinical research center (CRC) in a 12-month cohort study with quarterly study visits. Women in the cohort studies were required to use a condom plus a hormonal contraceptive method. HIV prevalence rates in the baseline cross-sectional surveys were high: 42% in Ladysmith, 46% in Edendale and 41% in Pinetown. Around 90% of study participants at each CRC reported one sex partner in the last 3 months, but only 14–30% stated that they were sure that none of their sex partners were HIV-positive. HIV incidence rates based on seroconversions over 12 months were 14.8/100 person-years (PY) (95% CI 9.7, 19.8) in Ladysmith, 6.3/100 PY (95% CI 3.2, 9.4) in Edendale, and 7.2/100 PY (95% CI 3.7, 10.7) in Pinetown. The 12-month pregnancy incidence rates (in the context of high reported contraceptive use) were: 5.7/100 PY (95% CI 2.6, 8.7) in Ladysmith, 3.1/100 PY (95% CI 0.9, 5.2) in Edendale and 6.3/100 PY (95% CI 3.0, 9.6) in Pinetown.

Conclusions/Significance

HIV prevalence and incidence remain high in peri-urban areas of KwaZulu-Natal.     

Patterns of Treatment Interruption among Patients with Multidrug-Resistant TB (MDR TB) and Association with Interim and Final Treatment Outcomes

Background

The reasons that patients with multidrug-resistant tuberculosis (MDR TB) miss treatment are multi-factorial and complex. Identifying patterns of treatment interruption that predict poor outcomes can be used to target program activities aiming to improve treatment adherence.

Objective

To characterize patterns of treatment interruption among MDR TB patients and determine the association between patterns and treatment outcomes.

Methods

Retrospective analysis of MDR TB patients. A treatment interruption was defined as any time that a patient missed a prescribed dose of treatment for at least 1 day but for a period of less than 2 consecutive months. Patients were characterized by the number, length and variability of interruptions, variability of time between interruptions, and percent of missed doses. Final treatment outcome was dichotomized as a successful (cured or completed) or poor outcome (defaulted, failed, or died). Risk ratios were calculated to determine the association between characteristics of treatment interruption and treatment outcomes. All analyses were conducted in 6 month treatment intervals.

Results

Only 7.0% of 583 patients completed treatment without interruption. Of the remaining 542 patients, the median time to the first interruption was 2 ½ months (70 days). In multivariate analysis, patients who had longer interruptions with sporadic variability during the 6–12 month or the 12–18 month treatment period had a significantly increased risk for poor outcomes compared to patients who had short, regular interruptions (RR_adj 4.37, 95% CI 1.2–15.8;  = 0.03 and RR_adj 3.38, 95% CI 1.6–7.1; p = 0.001, respectively). In addition, missing 10% or more of the prescribed doses during any 6 month period in the initial 18 months of therapy significantly increased the risk for poor outcomes (RR_adj range 1.55–2.35; p-value range 0.01–0.005).

Conclusion

Patients that miss more consecutive days of treatment with sporadic interruption patterns or a greater proportion of treatment are at an increased risk for poor treatment outcomes.     

Risk Factors for Poor Treatment Outcomes in Patients with MDR-TB and XDR-TB in China: Retrospective Multi-Center Investigation

Background

The treatment of patients with MDR- and XDR-TB is usually more complex, toxic and costly and less effective than treatment of other forms of TB. However, there is little information available on risk factors for poor outcomes in patients with MDR- and XDR-TB in China.

Methodology/Principal Findings

We retrospectively analyzed the clinical records of HIV-negative TB Patients with culture-proven MDR- or XDR-TB who were registered from July 2006 to June 2011 at five large-scale Tuberculosis Specialized Hospitals in China. Among 1662 HIV-seronegative TB cases which were culture-positive for M. tuberculosis complex and had positive sputum-smear microscopy results, 965 cases (58.1%) were DR-TB, and 586 cases (35.3%) were classified as having MDR-TB, accounting for 60.7% of DR-TB. 169 cases (10.2%) were XDR-TB, accounting for 17.5% of DR-TB, 28.8% of MDR-TB. The MDR-TB patients were divided into XDR-TB group (n=169) and other MDR-TB group (non-XDR MDR-TB) (n=417). In total, 240 patients (40.95%) had treatment success, and 346 (59.05%) had poor treatment outcomes. The treatment success rate in other MDR-TB group was 52.2%, significantly higher than that in the XDR-TB group (13%, P<0.001). In multivariate logistic regression analysis, poor outcomes were associated with duration of previous anti-TB treatment of more than one year (OR, 0.077; 95% CI, 0.011-0.499, P<0.001), a BMI less than 18.5 kg/m² (OR, 2.185; 95% CI, 1.372-3.478, P<0.001), XDR (OR, 13.368; 95% CI, 6.745-26.497, P<0.001), retreatment (OR, 0.171; 95% CI, 0.093-0.314, P<0.001), diabetes (OR, 0.305; 95% CI, 0.140-0.663, P=0.003), tumor (OR, 0.095; 95% CI, 0.011-0.795, P=0.03), decreased albumin (OR, 0.181; 95% CI, 0.118-0.295, P<0.001), cavitation (OR, 0.175; 95% CI, 0.108-0.286, P<0.001).

Conclusions/Significance

The patients with MDR-TB and XDR-TB have poor treatment outcomes in China.The presence of extensive drug resistance, low BMI, hypoalbuminemia, comorbidity, cavitary disease and previous anti-TB treatment are independent prognostic factors for poor outcome in patients with MDR-TB.     

Coadministration of Lopinavir/Ritonavir and Rifampicin in HIV and Tuberculosis Co-Infected Adults in South Africa

Background

In HIV-infected patients receiving rifampicin-based treatment for tuberculosis (TB), the dosage of lopinavir/ritonavir (LPV/r) is adjusted to prevent sub-therapeutic lopinavir concentrations. In this setting, South African clinicians were advised to administer super-boosted LPV/r (400 mg/400 mg) twice daily, instead of standard dosed LPV/r (400 mg/100 mg) twice daily. We sought to determine – in routine practice – the tolerability and HIV treatment outcomes associated with super-boosted LPV/r compared to unadjusted LPV/r in combination with rifampicin-based TB treatment.

Methodology/Principle Findings

We conducted a retrospective review of HIV-infected patients who receiving second-line ART with a LPV/r-containing regimen who required concomitant TB treatment. We identified 29 patients; the median age was 36 years (IQR 29–40), 22 (76%) were female, the median CD4 cell count and viral load at first-line ART failure was 86 cells/mm³ (IQR 21–159) and 39,457 copies/mL (IQR 6,025–157,500), respectively. According to physician preference, 15 (52%) of 29 patients received super-boosted LPV/r (400 mg/400 mg) every 12 hours during TB treatment and 14 (48%) of 29 patients received standard dose LPV/r (400 mg/100 mg) twice daily during TB treatment. Among patients who received super-boosted LPV/r there was a trend towards a higher rate of symptomatic transaminitis (27% vs. 7%; p = 0.3), gastrointestinal toxicity (20% vs. 0%; p = 0.2) and a significantly increased need for treatment discontinuation (47% vs. 7%; p = 0.035. The durability of coadministered treatment was significantly shorter in patients who received super-boosted lopinavir/ritonavir with TB treatment compared to patients who received standard lopinavir/ritonavir dosing (log rank, P = 0.036). The rate of virologic failure was not higher in patients with unadjusted LPV/r dosing.

Conclusions/Significance

We observed a high rate of toxicity and need for treatment discontinuation among patients on standard rifampicin-based TB treatment who received super-boosted LPV/r.     

High Prevalence of inhA Promoter Mutations among Patients with Drug-Resistant Tuberculosis in KwaZulu-Natal,South Africa

Background

Drug-resistant tuberculosis (TB) remains extremely difficult to treat because there are often few remaining active medications and limited diagnostic options to detect resistance. Resistance to isoniazid is typically caused by mutations in either katG or the inhA promoter. inhA mutations confer low-level resistance to isoniazid and cross-resistance to ethionamide while katG mutations confer high-level isoniazid resistance and no cross-resistance. Line Probe Assays (LPAs) that detect mutations in katG and inhA are currently performed on all positive TB cultures in KwaZulu-Natal province, South Africa, but the frequency of inhA mutations in drug-resistant TB patients has not been examined.

Methods

We sought to determine the proportion of patients who could potentially benefit from high-dose isoniazid and who may be resistant to ethionamide. We reviewed 994 LPA (Hain MTBDRplus) results at the TB reference laboratory in KwaZulu-Natal to determine the frequency of mutations in either katG or the inhA promoter. We stratified these results by drug-resistance category (i.e., MDR-TB, pre-XDR-TB, and XDR-TB) as determined by phenotypic drug-susceptibility testing.

Results

Among MDR- and XDR-TB isolates, the prevalence of inhA mutations without a concurrent katG mutation was 14.8% and 10.3% respectively. The prevalence of inhA mutations with OR without a katG mutation was 30.3% and 82.8%, respectively.

Conclusion

More than 10% of patients with MDR- and XDR-TB may benefit from high-dose isoniazid. Although ethionamide is empirically included in all MDR- and XDR-TB regimens, nearly a third of MDR-TB patients and a majority of XDR-TB patients likely have resistance to ethionamide. Laboratories performing line probe assays should report specific band patterns so that clinicians may adjust treatment regimens accordingly.     

Need for Timely Paediatric HIV Treatment within Primary Health Care in Rural South Africa

Background

In areas where adult HIV prevalence has reached hyperendemic levels, many infants remain at risk of acquiring HIV infection. Timely access to care and treatment for HIV-infected infants and young children remains an important challenge. We explore the extent to which public sector roll-out has met the estimated need for paediatric treatment in a rural South African setting.

Methods

Local facility and population-based data were used to compare the number of HIV infected children accessing HAART before 2008, with estimates of those in need of treatment from a deterministic modeling approach. The impact of programmatic improvements on estimated numbers of children in need of treatment was assessed in sensitivity analyses.

Findings

In the primary health care programme of HIV treatment 346 children <16 years of age initiated HAART by 2008; 245(70.8%) were aged 10 years or younger, and only 2(<1%) under one year of age. Deterministic modeling predicted 2,561 HIV infected children aged 10 or younger to be alive within the area, of whom at least 521(20.3%) would have required immediate treatment. Were extended PMTCT uptake to reach 100% coverage, the annual number of infected infants could be reduced by 49.2%.

Conclusion

Despite progress in delivering decentralized HIV services to a rural sub-district in South Africa, substantial unmet need for treatment remains. In a local setting, very few children were initiated on treatment under 1 year of age and steps have now been taken to successfully improve early diagnosis and referral of infected infants.     

Economic Outcomes of Patients Receiving Antiretroviral Therapy for HIV/AIDS in South Africa Are Sustained through Three Years on Treatment

Background

Although the medical outcomes of antiretroviral therapy (ART) for HIV/AIDS are well described, less is known about how ART affects patients'' economic activities and quality of life, especially after the first year on ART. We assessed symptom prevalence, general health, ability to perform normal activities, and employment status among adult antiretroviral therapy patients in South Africa over three full years following ART initiation.

Methodology/Principal Findings

A cohort of 855 adult pre-ART patients and patients on ART for <6 months was enrolled and interviewed an average of 4.4 times each during routine clinic visits for up to three years after treatment initiation using an instrument designed for the study. The probability of pain in the previous week fell from 74% before ART initiation to 32% after three years on ART, fatigue from 66% to 12%, nausea from 28% to 4%, and skin problems from 55% to 10%. The probability of not feeling well physically yesterday fell from 46% to 23%. Before starting ART, 39% of subjects reported not being able to perform their normal activities sometime during the previous week; after three years, this proportion fell to 10%. Employment rose from 27% to 42% of the cohort. Improvement in all outcomes was sustained over 3 years and for some outcomes increased in the second and third year.

Conclusions/Significance

Improvements in adult ART patients'' symptom prevalence, general health, ability to perform normal activities, and employment status were large and were sustained through the first three years on treatment. These results suggest that some of the positive economic and social externalities anticipated as a result of large-scale treatment provision, such as increases in workforce participation and productivity and the ability of patients to carry on normal lives, may indeed be accruing.     

Monitoring of Antiretroviral Therapy and Mortality in HIV Programmes in Malawi,South Africa and Zambia: Mathematical Modelling Study

Objectives

Mortality in patients starting antiretroviral therapy (ART) is higher in Malawi and Zambia than in South Africa. We examined whether different monitoring of ART (viral load [VL] in South Africa and CD4 count in Malawi and Zambia) could explain this mortality difference.

Design:

Mathematical modelling study based on data from ART programmes.

Methods

We used a stochastic simulation model to study the effect of VL monitoring on mortality over 5 years. In baseline scenario A all parameters were identical between strategies except for more timely and complete detection of treatment failure with VL monitoring. Additional scenarios introduced delays in switching to second-line ART (scenario B) or higher virologic failure rates (due to worse adherence) when monitoring was based on CD4 counts only (scenario C). Results are presented as relative risks (RR) with 95% prediction intervals and percent of observed mortality difference explained.

Results

RRs comparing VL with CD4 cell count monitoring were 0.94 (0.74–1.03) in scenario A, 0.94 (0.77–1.02) with delayed switching (scenario B) and 0.80 (0.44–1.07) when assuming a 3-times higher rate of failure (scenario C). The observed mortality at 3 years was 10.9% in Malawi and Zambia and 8.6% in South Africa (absolute difference 2.3%). The percentage of the mortality difference explained by VL monitoring ranged from 4% (scenario A) to 32% (scenarios B and C combined, assuming a 3-times higher failure rate). Eleven percent was explained by non-HIV related mortality.

Conclusions

VL monitoring reduces mortality moderately when assuming improved adherence and decreased failure rates.     

Comparison of Treatment Outcomes of New Smear-Positive Pulmonary Tuberculosis Patients by HIV and Antiretroviral Status in a TB/HIV Clinic,Malawi

Background

Smear-positive pulmonary TB is the most infectious form of TB. Previous studies on the effect of HIV and antiretroviral therapy on TB treatment outcomes among these highly infectious patients demonstrated conflicting results, reducing understanding of important issues.

Methods

All adult smear-positive pulmonary TB patients diagnosed between 2008 and 2010 in Malawi’s largest public, integrated TB/HIV clinic were included in the study to assess treatment outcomes by HIV and antiretroviral therapy status using logistic regression.

Results

Of 2,361 new smear-positive pulmonary TB patients, 86% had successful treatment outcome (were cured or completed treatment), 5% died, 6% were lost to follow-up, 1% failed treatment, and 2% transferred-out. Overall HIV prevalence was 56%. After adjusting for gender, age and TB registration year, treatment success was higher among HIV-negative than HIV-positive patients (adjusted odds ratio 1.49; 95% CI: 1.14–1.94). Of 1,275 HIV-infected pulmonary TB patients, 492 (38%) received antiretroviral therapy during the study. Pulmonary TB patients on antiretroviral therapy were more likely to have successful treatment outcomes than those not on ART (adjusted odds ratio : 1.83; 95% CI: 1.29–2.60).

Conclusion

HIV co-infection was associated with poor TB treatment outcomes. Despite high HIV prevalence and the integrated TB/HIV setting, only a minority of patients started antiretroviral therapy. Intensified patient education and provider training on the benefits of antiretroviral therapy could increase antiretroviral therapy uptake and improve TB treatment success among these most infectious patients.     

High Rate of Hypothyroidism in Multidrug-Resistant Tuberculosis Patients Co-Infected with HIV in Mumbai,India

Background

Adverse events (AEs) among HIV-infected patients with multidrug-resistant tuberculosis (MDR-TB) receiving anti-TB and antiretroviral treatments (ART) are under-researched and underreported. Hypothyroidism is a common AE associated with ethionamide, p-aminosalicylic acid (PAS), and stavudine. The aim of this study was to determine the frequency of and risk factors associated with hypothyroidism in HIV/MDR-TB co-infected patients.

Methods

This was a prospective, observational cohort study, using routine laboratory data in a Médecins Sans Frontières (MSF) clinic in collaboration with Sewri TB Hospital, Mumbai, India. Hypothyroidism was defined as a thyroid stimulating hormone (TSH) result >10 mIU/L at least once during treatment. Patients having a baseline result and one additional result after 3 months were eligible for enrolment.

Results

Between October 2006 and March 2013, 116 patients were enrolled, 69 of whom were included. The median (IQR) age was 38 years (34-43) and 61% were male. By March 2013, 37/69 (54%) had hypothyroidism after at least 90 days of treatment. Age, gender, CD4 counts and stavudine-based ART were not associated with the occurrence of hypothyroidism in multivariate models. The co-administration of PAS and ethionamide was found to double the risk of hypothyroidism (RR: 1.93, 95% CI: 1.06-3.54).

Discussion

High rate of hypothyroidism was recorded in a Mumbai cohort of MDR-TB/HIV co-infected patients on treatment. This is a treatable and reversible AE, however, it may go undiagnosed in the absence of regular monitoring. Care providers should not wait for clinical symptoms, as this risks compromising treatment adherence. Simple, affordable and reliable point-of-care tools for measuring TSH are needed, especially in high MDR-TB burden countries. Our findings suggest the need for TSH screening at baseline, three months, six months, and every six months thereafter for HIV-infected patients on MDR-TB treatment regimens containing PAS and/or ethionamide, until newer, safer and more efficacious MDR-TB regimens become available.     

The Prevalence and Drug Sensitivity of Tuberculosis among Patients Dying in Hospital in KwaZulu-Natal,South Africa: A Postmortem Study

Background

Tuberculosis is the leading cause of death in South Africa by death notification, but accurate diagnosis of tuberculosis is challenging in this setting of high HIV prevalence. We conducted limited autopsies on young adults dying in a single public hospital in the province of KwaZulu-Natal between October 2008 and August 2009 in order to estimate the magnitude of deaths attributable to tuberculosis.

Methods and Findings

We studied a representative sample of 240 adult inpatients (aged 20–45 years) dying after admission to Edendale Hospital. Limited autopsies included collection of respiratory tract secretions and tissue by needle core biopsies of lung, liver, and spleen. Specimens were examined by fluorescent microscopy for acid-fast bacilli and cultured in liquid media; cultures positive for M. tuberculosis were tested for drug susceptibility to first- and second-line antibiotics. Ninety-four percent of our study cohort was HIV seropositive and 50% of decedents had culture-positive tuberculosis at the time of death. Fifty percent of the participants were on treatment for tuberculosis at the time of death and 58% of these treated individuals remained culture positive at the time of death. Of the 50% not receiving tuberculosis treatment, 42% were culture positive. Seventeen percent of all positive cultures were resistant to both isoniazid and rifampin (i.e., multidrug resistant); 16% of patients dying during the initiation phase of their first ever course of tuberculosis treatment were infected with multidrug-resistant bacilli.

Conclusions

Our findings reveal the immense toll of tuberculosis among HIV-positive individuals in KwaZulu-Natal. The majority of decedents who remained culture positive despite receiving tuberculosis treatment were infected with pan-susceptible M. tuberculosis, suggesting that the diagnosis of tuberculosis was made too late to alter the fatal course of the infection. There is also a significant burden of undetected multidrug-resistant tuberculosis among HIV-coinfected individuals dying in this setting. New public health approaches that improve early diagnosis of tuberculosis and accelerate the initiation of treatment are urgently needed in this setting. Please see later in the article for the Editors'' Summary