An Updated Systematic Review and Meta-analysis on the Treatment of Active Tuberculosis in Patients with HIV Infection.

Clin Infect Dis. 2012 Jul 19;

Authors: Khan FA, Minion J, Al-Motairi A, Benedetti A, Harries AD, Menzies D

Abstract
Background. Human immunodeficiency virus infection increases the risk of poor outcomes in active tuberculosis. We updated a systematic review and meta-analysis assessing the effects of duration of rifamycins, schedule of dosing, and antiretroviral therapy (ART), on failure, relapse, death during treatment, and acquired drug resistance (ADR) in patients with HIV and active TB.Methods. We searched for randomized control trials (RCTs) and observational studies published between 2008 and November 2011. We pooled risk differences (RD) from RCTs comparing rifampin for ≥9 and 6 months. Within strata of the 3 treatment covariates, we calculated pooled risks and adjusted odds ratios (aOR) using outcomes from RCTs and observational studies.Results. After screening 2293 citations, 7 studies were added in the update. Risk of relapse was lowered with rifampin treatment for ≥9 as compared to 6 months (pooled RD = -9.1%, 95%CI[-16.5,-1.8]). Odds of relapse were higher with shorter durations of rifamycins (aOR 2 vs. ≥8 months =5.0,[1.9,13.2]; 6 vs. ≥8 months =2.4,[1.2,5.0]), and in the absence of ART (aOR =14.3,[2.1,97.8]). Post-hoc meta-regression restricted to arms with ART demonstrated no associations between rifamycin duration, dosing schedule and the outcomes.Conclusion. In patients with HIV and active TB, ART reduces the risk of TB relapse. Use of rifamycins for ≥8 months and daily dosing in the intensive phase also improve TB treatment outcomes; however, a paucity of evidence makes their importance less clear for patients on ART. There is an urgent need to increase the number of co-infected patients receiving ART.

PMID: 22820541 [PubMed - as supplied by publisher]

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Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society-USA panel.

JAMA. 2012 Jul 25;308(4):387-402

Authors: Thompson MA, Aberg JA, Hoy JF, Telenti A, Benson C, Cahn P, Eron JJ, Günthard HF, Hammer SM, Reiss P, Richman DD, Rizzardini G, Thomas DL, Jacobsen DM, Volberding PA

Abstract
CONTEXT: New trial data and drug regimens that have become available in the last 2 years warrant an update to guidelines for antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected adults in resource-rich settings.
OBJECTIVE: To provide current recommendations for the treatment of adult HIV infection with ART and use of laboratory-monitoring tools. Guidelines include when to start therapy and with what drugs, monitoring for response and toxic effects, special considerations in therapy, and managing antiretroviral failure. DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION: Data that had been published or presented in abstract form at scientific conferences in the past 2 years were systematically searched and reviewed by an International Antiviral Society-USA panel. The panel reviewed available evidence and formed recommendations by full panel consensus.
DATA SYNTHESIS: Treatment is recommended for all adults with HIV infection; the strength of the recommendation and the quality of the evidence increase with decreasing CD4 cell count and the presence of certain concurrent conditions. Recommended initial regimens include 2 nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine) plus a nonnucleoside reverse transcriptase inhibitor (efavirenz), a ritonavir-boosted protease inhibitor (atazanavir or darunavir), or an integrase strand transfer inhibitor (raltegravir). Alternatives in each class are recommended for patients with or at risk of certain concurrent conditions. CD4 cell count and HIV-1 RNA level should be monitored, as should engagement in care, ART adherence, HIV drug resistance, and quality-of-care indicators. Reasons for regimen switching include virologic, immunologic, or clinical failure and drug toxicity or intolerance. Confirmed treatment failure should be addressed promptly and multiple factors considered.
CONCLUSION: New recommendations for HIV patient care include offering ART to all patients regardless of CD4 cell count, changes in therapeutic options, and modifications in the timing and choice of ART in the setting of opportunistic illnesses such as cryptococcal disease and tuberculosis.

PMID: 22820792 [PubMed - indexed for MEDLINE]

The combination of sulfamethoxazole, trimethoprim, and isoniazid or rifampin is bactericidal and prevents the emergence of drug resistance in Mycobacterium tuberculosis.

Antimicrob Agents Chemother. 2012 Jul 23;

Authors: Vilchèze C, Jacobs WR

Abstract
The challenges of developing new drugs to treat tuberculosis (TB) are indicated by the relatively low number of candidates entering clinical trials in the past decade. To overcome these issues, we have re-examined two FDA-approved antibacterial drugs, sulfamethoxazole (SMX) and trimethoprim (TMP), for TB treatment. SMX and TMP inhibit folic acid biosynthesis and are used in combination to treat infections of the respiratory-, urinary-, and gastrointestinal tracts. The minimum inhibitory concentrations of SMX and TMP, alone and in combination, were determined against drug-susceptible, multidrug-resistant (MDR) and extensively drug-resistant M. tuberculosis strains. While TMP was not effective against M. tuberculosis alone, the combination TMP/SMX was bacteriostatic against M. tuberculosis. Surprisingly, the combination of SMX and TMP was also active against a subset of MDR M. tuberculosis strains. Treatment of M. tuberculosis with a combination of TMP/SMX and the first-line anti-TB drugs isoniazid or rifampin was bactericidal, demonstrating that the combination of TMP and SMX with isoniazid or rifampin was not antagonistic. Moreover, the addition of SMX/TMP in combination with either isoniazid or rifampin also prevented the emergence of drug resistance in vitro. In conclusion, this study further illustrates the opportunity to re-evaluate the activity of TMP/SMX in vivo to prevent the emergence of drug-resistant M. tuberculosis.

PMID: 22825115 [PubMed - as supplied by publisher]

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A potential role for vitamin D as a therapeutic immunomodulator in tuberculosis (TB) has been recognised for over 150 years, but has only recently returned to the centre of the research arena due to the increasing awareness of the global vitamin D deficiency epidemic. As early as birth a child is often deficient in vitamin D, which may not only affect their bone metabolism but also modulate their immune function, contributing to the increased susceptibility to many infections seen early in life. Recent studies have begun to explain the mechanisms by which vitamin D affects immunity.

Antimicrobial peptides are induced in conjunction with stimulation of innate pattern recognition receptors enhancing immunity to particular infections. In contrast the role of vitamin D within the adaptive immune response appears to be more regulatory in function, perhaps as a mechanism to reduce unwanted inflammation. In this paper we focus on the effect of vitamin D on immunity to TB.

Where much of the attention has been paid by past reviews to the role of vitamin D in adult TB patients, this paper, where possible, focuses on research in paediatric populations.