Changing Clinical Presentation and Survival in HIV-Associated Tuberculosis After Highly Active Antiretroviral Therapy

Girardi, Enrico; Palmieri, Fabrizio; Cingolani, Antonella; Ammassari, Adriana; Petrosillo, Nicola; Gillini, Laura; Zinzi, Daniela; Luca, Andrea De; Antinori, Andrea; Ippolito, Giuseppe

doi:10.1097/00126334-200104010-00006

Cited by 49 publications

(19 citation statements)

References 29 publications

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“…This finding shows that HIV-infected TB patients treated with ART had almost 23% better survival compared with those who were not treated with ART. The benefit of ART in reducing the death rates of TB/HIV co-infected patients have been well documented in other studies [5,7,30–32]. The widespread use of antiretroviral therapy since 1996 has markedly improved the survival of HIV-infected patients both in developing and developed countries by reducing the number of deaths from many opportunistic infections.…”

Section: Discussionmentioning

confidence: 80%

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

Ismail

Bulgiba

2013

PLoS ONE

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BackgroundMortality 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.MethodsWe 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.ResultsOf 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)ConclusionTB/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.

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Section: Discussionmentioning

confidence: 80%

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

Ismail

Bulgiba

2013

PLoS ONE

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“…In HIV-tuberculosis co-infected patients, antiretroviral therapy may be initiated at the same time or soon after tuberculosis treatment initiation. However, antiretrovirals are often deferred until completion of the intensive phase of tuberculosis treatment because of concerns related to immune reconstitution inflammatory syndrome (IRIS) 2–3 , high pill burden and overlapping side effects 4 , when three antiretrovirals are added to the standard four anti-tuberculosis drugs. This may result in interruptions or discontinuations in AIDS or tuberculosis treatment, which can lead to drug resistance and potentially limit future therapeutic options 5–6 , but must be weighed against the risk of increased mortality early in the treatment of tuberculosis…”

mentioning

confidence: 99%

Integration of Antiretroviral Therapy with Tuberculosis Treatment

Karim

Naidoo²,

Grobler³

et al. 2011

N Engl J Med

434

274

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Background We previously reported that integrating antiretroviral therapy (ART) with tuberculosis treatment reduces mortality. However, optimal time to initiate ART during tuberculosis treatment remains contentious. Methods To address this, we conducted a 3-arm, open-label randomized controlled trial in South Africa in acid-fast bacilli smear positive patients (n=642) with HIV and CD4+ counts <500 cells/mm3. Findings on the early therapy group (ART initiated within 4 weeks of tuberculosis treatment initiation, n=214) and late therapy group (ART initiated within the first 4 weeks of the continuation phase of tuberculosis treatment, n=215) are presented here. Results Median CD4+ count and viral load at baseline was 150 cells/mm3 and 161000 copies/ml, being similar in both groups. Incidence rate of AIDS or death was 6.9 (18/259.4) and 7.8 (19/244.2) per 100 person-years in the early and late therapy groups respectively (Incidence Rate Ratio (IRR)=0.89; 95%Confidence Interval (95%CI): 0.44,1.79; P=0.73). However, in patients with CD4+ counts <50 cells/mm3, the incidence rates of AIDS or death were 8.5 (early) and 26.3 (late) per 100 person-years (IRR=0.32; 95%CI: 0.07,1.13; P=0.06). Immune reconstitution inflammatory syndrome (IRIS) incidence rates were 20.2 (early) and 7.7 (late) per 100 person-years (IRR=2.62; 95%CI: 1.48,4.82; P<0.001). Adverse events requiring antiretroviral drug switches occurred in 10 (early) and 1 (late) patients (P=0.006). Conclusions The benefits of AIDS-free survival balanced against the risks of IRIS and ART-related adverse events, support early ART initiation in patients with CD4+ counts <50 cells/mm3 and deferred ART initiation to the continuation phase of tuberculosis treatment when CD4+ counts are higher.

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“…High pill burden due to multidrug regimens, an increased risk of developing TB-associated immune reconstitution inflammatory syndrome (IRIS) (Laureillard et al, 2013), overlapping drug-related side effects (Girardi et al, 2001) and potential adverse drug interactions (Piscitelli & Gallicano, 2001) are some of the aspects of therapy that make the implementation of TasP complex in patients with HIV/(DR-)TB co-infection. For instance, an increased risk of developing TB-IRIS, a paradoxical clinical deterioration in patients following ART treatment initiation during TB treatment (Laureillard et al, 2013;Meintjes et al, 2008;Naidoo et al, 2012), particularly in patients with very low CD4 count, is an imminent concern that requires careful consideration of the potential benefits and risks of initiating ART early as it may be life-threatening in certain circumstances, such as in cases with cerebral oedema and depressed level of consciousness or severe respiratory failure (Lawn et al, 2013;Meintjes et al, 2008;Naidoo et al, 2012).…”

Section: Drug-drug Interaction Effects and Drug Side Effectsmentioning

confidence: 99%

Programmatic and ethical challenges in the implementation of treatment-as-prevention in the context of HIV and drug-resistant tuberculosis co-infection in sub-Saharan Africa

Melesse

Becker

McClarty

et al. 2014

Global Public Health

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There is limited literature on programmatic challenges in the implementation of a treatment-as-prevention (TasP) strategy among human immunodeficiency virus (HIV) and drug-resistant tuberculosis (DR-TB) co-infected individuals in sub-Saharan Africa (SSA). This paper highlights specific programmatic challenges surrounding the implementation of this strategy among HIV and DR-TB co-infected populations in SSA. In SSA, limitations in administrative, human and financial resources and poor health infrastructure, as well as increased duration and complexity of providing long-term treatment for HIV individuals co-infected with DR-TB, pose substantial challenges to the implementation of a TasP strategy and warrant further investigation. A comprehensive approach must be devised to implement TasP strategy, with special attention paid to the sizable HIV and DR-TB co-infected populations. We suggest that evidence-informed and human rights-based guidelines for participant protection and strategies for programme delivery must be developed and tailored to maximise the benefits to those most at risk of developing HIV and DR-TB co-infection. Assessing regional circumstances is crucial, and TasP programmes in the region should be complemented by combined prevention strategies to achieve the intended goals.

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Changing Clinical Presentation and Survival in HIV-Associated Tuberculosis After Highly Active Antiretroviral Therapy

Abstract: Cases of HIV-associated TB occurring in patients with advanced immunosuppression and presenting with atypical radiologic appearance tend to be relatively less common in the HAART era. HAART is a major factor in prolonging survival in these patients.

Cited by 49 publications

References 29 publications

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

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

Integration of Antiretroviral Therapy with Tuberculosis Treatment

Programmatic and ethical challenges in the implementation of treatment-as-prevention in the context of HIV and drug-resistant tuberculosis co-infection in sub-Saharan Africa

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