Preventive therapy for tuberculosis in HIV infected individuals

The increased risk of developing tuberculosis (TB) among those infected with HIV has prompted a need to reconsider the institution of preventive therapy/chemoprophylaxis with one or more antituberculosis drugs. Prior to the initiation of preventive therapy for tuberculosis, it is essential to rule out active TB. The target population for chemoprophylaxis among HIV seropositives includes all Mantoux (PPD) positive individuals who do not have active tuberculosis and could include all PPD negative individuals living in high prevalence region for TB. The optimal duration of preventive therapy with single drug isoniazid, daily or twice weekly, should be greater than six months to provide the maximum degree of protection against tuberculosis. The effectiveness of preventive therapy should be evaluated at regular intervals by monitoring patients for drug adherence, drug toxicity and for the development of tuberculosis. Though the impact of preventive therapy on an individual basis may be rather small, widespread implementation would have substantial impact on morbidity due to tuberculosis and some impact on mortality. Till the vast majority of HIV positive individuals in the world can access antiretroviral therapy, preventive therapy for tuberculosis should be offered at voluntary counselling and testing centres, as part of a package of care that includes prophylaxis and treatment of opportunistic infections, nutritional support and counselling

HIV-Associated Tuberculosis: Clinical Update

The human immunodeficiency virus (HIV) epidemic has led to an increase in the incidence of tuberculosis globally, particularlyin sub-Saharan Africa. Coinfection with HIV leads to difficulties in both the diagnosis and treatment of tuberculosis. Becauseof the poor performance of sputum smear microscopy in HIV-infected patients, more sensitive tests—such as liquid culturesystems, nucleic acid amplification assays, and detection of mycobacterial products in various body fluids—are being inves-tigated. The treatment of coinfected patients requires antituberculosis and antiretroviral drugs to be administered concom-itantly; challenges include pill burden and patient compliance, drug interactions, overlapping toxic effects, and immunereconstitution syndrome. Both multidrug-resistant and extensively drug-resistant tuberculosis can spread rapidly among animmunocompromised population, with resulting high mortality rates. Current guidelines recommend starting antiretroviraltreatment within a few weeks of antituberculosis therapy for patients with CD4 cell counts!350 cells/mL; however, importantquestions about the drug regimens and timing of antiretroviral therapy remain. Ongoing trials may answer many of theseunresolved questions

Gender differences in perceived health related quality of life among persons living with HIV

In the era of HlV/AlDS and in the context of the developing world HIV/AIDS has led to a pandemic. HIV antiretroviral drugs are inaccessible and unaffordable and the only choice that health care providers have is to work towards improving the quality of life of individuals as long as they live with this dreaded disease. This study on 203 seropositive individuals, 102 women and 101 men, was undertaken to find out the differences in the quality of life perceived by women and men living with HIV/AIDS. The WHOQOL-BREF scale was used to assess the quality of life. The findings from this study reveal that men report a poor quality of life in the psychological domain (p<0.01) while women in the sociological domain (p=0.03). The stage of illness does not seem to influence quality of life among women and men. The findings emphasize the need for health providers to assess the QOL among people living with HIV/AIDS. This information would be helpful in planning effective intervention strategies for men and women living with HlV/AlDS in order to be ensured of a quality of life

Serum neopterin levels in HIV infected patients with & without tuberculosis.

Background & objective : Three categories of prognostic markers are best documented as having significance in relation to prognosis of HIV infection. These include HIV viral load, CD4 T-cell levels and plasma levels of soluble markers of immune activation. The plasma activation markers, like neopterin, tumor necrosis factor alpha (TNF-α), interleukins etc., are products of cytokine activity and represent immunologic changes throughout the body. There is not much information available on serum neopterin estimation in patients infected with both HIV and tuberculosis (TB), though neopterin levels are known to be elevated in pulmonary TB patients. In this study we attempted to correlate neopterin levels with the presence of tuberculosis in HIV infected and uninfected individuals and studied the changes after antituberculosis treatment. Methods : Serum neopterin concentrations were measured by high performance liquid chromatography (HPLC) in 25 HIV-seropositive (HIV-TB) and 10-seronegative (TB) patients with tuberculosis before, during and at the end of antituberculosis therapy (ATT). S-neo was also measured in 10 HIV-seropositive asymptomatic individuals and 10 healthy controls. The results were correlated with clinical, bacteriological and immunological status. Results : All TB patients regardless of HIV status had elevated s-neo concentrations at diagnosis, which declined gradually during treatment. Patients with HIV/TB with CD4 counts < 200/mm3 had the highest levels at baseline with a steep fall during treatment. The median level at the end of treatment was significantly higher in HIV/TB than in TB patients, despite clinical improvement and bacteriological clearance of Mycobacterium tuberculosis. HIV infected asymptomatic individuals had neopterin levels that were higher than healthy controls but lower than HIV-TB patients. Interpretation & conclusion : Serum neopterin levels are elevated in HIV-positive patients, with the highest levels in those with tuberculosis and CD4 counts < 200/mm3. Though the levels decrease with anti tuberculosis therapy, persistently elevated levels indicate progressive HIV disease and a poor prognosis

Urine levels of rifampicin & isoniazid in asymptomatic HIV-positive individuals

Background & objectives: AIDS and its associated gastrointestinal complications may impair the absorption of anti-tuberculosis (TB) drugs. Impaired absorption of anti-TB drugs could lead to low drug exposure, which might contribute to acquired drug resistance and reduced effectiveness of anti-TB treatment. The aim of this study was to obtain information on the status of absorption of rifampicin (RMP) and isoniazid (INH) in asymptomatic HIV- positive individuals, who are less immunocompromised. The D-xylose absorption test was also carried out to assess the absorptive capacity of intestive. Methods: The absorption of RMP, INH and D-xylose was studied in 15 asymptomatic HIV- positive individuals with CD4 cell counts > 350 cells/mm3 and 16 healthy volunteers, after oral administration of single doses of RMP (450 mg), INH (300 mg) and D-xylose (5 g). Urine was collected up to 8 h after drug administration. Percentage dose of the drugs and their metabolites and D-xylose excreted in urine were calculated. Results: A significant reduction in the urinary excretion of INH and D-xylose in HIV-positive persons compared to healthy volunteers was observed. The per cent dose of RMP and its metabolite, desacetyl RMP was also lower in HIV-positive persons compared to healthy volunteers, but this difference was not statistically significant. Interpretation & conclusion: Decreased urinary excretion of D-xylose and INH are suggestive of intestinal malabsorption in HIV-positive individuals. HIV infection could cause malabsorption of anti-TB drugs even at an early stage of the disease. The clinical implications of these findings need to be confirmed in larger studies

Sensitivity & specificity of combination testing algorithms for HIV in a tuberculosis clinic

Introduction: Co-management of tuberculosis (TB) and HIV is complicated by pharmacologic drug interactions between rifampicin (RMP) and certain classes of antiretroviral agents. The NNRTIs Nevirapine (NVP) or Efavirenz (EFV), used to HIV infection, are known to induce the CYP 450 enzyme system. Thus when RMP is co-administered along with NVP or EFV, the bioavailability of RMP could be lowered leading to drug resistance and treatment failure. Objectives: To study the steady state pharmacokinetics of RMP in HIV and HIV-TB patients receiving antiretroviral regimens containing NVP or EFV respectively. Methods: The study population comprised of HIV and HIV-TB patients undergoing antiretroviral treatment with NVP and EFV containing regimens respectively. These patients were also receiving concomitant RMP. Rifampicin was estimated by HPLC in blood collected at different time points after drug administration. The pharmacokinetic variables of RMP were calculated using WinNonlin software. Results & Conclusions: Co-administration of NVP or EFV did not alter the pharmacokinetics of RMP in HIV and HIV-TB patients, suggesting that the dose of RMP need not be altered during antiretroviral treatment with NVP or EFV

Impact of HIV Infection on Radiographic Features in Patients with Pulmonary Tuberculosis

Background. There is insufficient data on the radiographic presentation of tuberculosis in human immunodeficiency virus (HIV) infected patients from India. Methods. We examined the chest radiographs of 181 patients including 82 HIV positives with newly diagnosed sputum culture positive pulmonary tuberculosis before and after the completion of anti-tuberculosis treatment (ATT). Patients with smear/culture positive pulmonary tuberculosis were treated with Revised National Tuberculosis Control Programme (RNTCP) Cat-I regimen (2EHRZ3/4HR3). An independent assessor blinded to HIV and clinical status of patients read the radiographs. Results. At presentation, HIV seropositive patients were significantly more likely to have normal chest radiographs (14.2% vs 0), miliary tuberculosis (10.7% vs 1%) and pleural effusion (16.6% vs 3%), and less likely to have cavitation (17.8% vs 39.4%) as compared to HIV negative patients. At the end of treatment, HIV positive patients were more likely to have normal radiographs (42.8% vs 1.2%), and less likely to have fibrosis (17.8% vs 42.5%). Conclusions. The radiographic presentation of pulmonary tuberculosis in HIV-infected patients is atypical with less cavitation, and more dissemination. On completion of ATT, patients with HIV have less radiographic sequelae in the form of fibrosis. These features may be due to the reduced inflammatory response that patients with HIV infection may be able to mount

Acetylator status influences bioavailability of isoniazid in patients with advanced HIV disease

Patients with advanced HIV disease may exhibit malabsorption of anti-tuberculosis(TB) drugs. We evaluated the effect of isoniazid (INH) acetylator status on the bioavailability of INH in HIV-infected patients with and without tuberculosis, based on urinary excretion of the drug. Estimation of INH in urine collected up to 8 hours after oral administration of 300 mg INH were undertaken in 23 TB, 40 HIV and 26 HIV-TB patients. Determination of acetylator status of all these patients was also carried by differential estimations of INH and acetyl INH in urine collected between 5 and 6 hours after oral administration of 300 mg INH. Both slow and rapid acetylators in HIV and HIV-TB groups had significantly lower concentration of INH in urine compared to TB patients. The percent decrease in urinary excretion of INH was significantly higher in rapid than in slow acetylators, when compared to the corresponding TB patients. Acetylator status has an impact on the bioavailability of INH. Malbsorption in patients with advanced HIV disease may lead to decreased bioavailability of INH, particularly in rapid acetylators. Urinary estimation of INH provides reliable information on the bioavailability of the drug

Study of ABCB1 polymorphism (C3435T) in HIV-1-infected individuals from South India

Studies on P-glycoprotein expression and function have revealed that a single nucleotide polymorphism (SNP) in the human ABCB1 gene at 3435 (C > T) results in altered expression and function of P-glycoprotein [1, 2].There have been reports of lower nelfinavir and efavirenz (EFV) concentrations associated with TT genotypes (mutant) of ABCB1 C3435T polymorphism [3, 4].Frequency distribution of this polymorphism is known to vary across populations [3, 5, 6]. We report the genotype distribution of ABCB1 C3435T in 179 individuals (126 HIV-infected and 53 healthy) from South India. The polymorphism was correlated with plasma 12 h EFV and 2 h nevirapine (NVP) concentrations in 55 and 71 patients, respectively. Plasma EFV and NVP were estimated by HPLC [7, 8]. Genotyping was carried out by PCR-RFLP [9]

Smoking, alcohol use disorder and tuberculosis treatment outcomes: A dual co-morbidity burden that cannot be ignored

BackgroundMore than 20% of tuberculosis (TB) disease worldwide may be attributable to smoking and alcohol abuse. India is the second largest consumer of tobacco products, a major consumer of alcohol particularly among males, and has the highest burden of TB globally. The impact of increasing tobacco dose, relevance of alcohol misuse and past versus current or never smoking status on TB treatment outcomes remain inadequately defined.MethodsWe conducted a multi-centric prospective cohort study of newly diagnosed adult pulmonary TB patients initiated on TB treatment and followed for a minimum of 6 months to assess the impact of smoking status with or without alcohol abuse on treatment outcomes. Smokers were defined as never smokers, past smokers or current smokers. Alcohol Use Disorder Identification Test (AUDIT) scores were used to assess alcohol misuse. The association between smoking status and treatment outcomes was assessed in univariate and multivariate random effects poisson regression models.ResultsOf 455 enrolled, 129 (28%) had a history of smoking with 94 (20%) current smokers and 35 (8%) past smokers. Unfavourable treatment outcomes were significantly higher among past and current smokers as compared to never smokers. Specifically, the risk of treatment failure was significantly higher among past smokers (aIRR = 2.66, 95% CI: 1.41-4.90, p = 0.002), recurrent TB among current smokers (aIRR = 2.94, 95% CI: 1.30-6.67, p = 0.010) and death among both past (2.63, 95% CI: 1.11-6.24, p = 0.028) and current (aIRR = 2.59, 95% CI: 1.29-5.18, p = 0.007) smokers. Furthermore, the combined effect of alcohol misuse and smoking on unfavorable treatment outcomes was significantly higher among past smokers (aIRR: 4.67, 95% CI: 2.17-10.02, pConclusionPast and current smoking along with alcohol misuse have combined effects on increasing the risk of unfavourable TB treatment outcomes. Innovative interventions that can readily address both co-morbidities are urgently needed