HIV and tuberculosis in India

The global impact of the converging dual epidemics of tuberculosis (TB) and human immunodefi ciency virus (HIV) is one of the major public health challenges of our time. The World Health Organization (WHO) reports 9.2 million new cases of TB in 2006 of whom 7.7% were HIV-infected. Tuberculosis is the most common opportunistic infection in HIV-infected patients as well as the leading cause of death. Further, there has been an increase in rates of drug resistant tuberculosis, including multi-drug (MDRTB) and extensively drug resistant TB (XDRTB), which are diffi cult to treat and contribute to increased mortality. The diagnosis of TB is based on sputum smear microscopy, a 100-year old technique and chest radiography, which has problems of specifi city. Extra-pulmonary, disseminated and sputum smear negative manifestations are more common in patients with advanced immunosuppression. Newer diagnostic tests are urgently required that are not only sensitive and specifi c but easy to use in remote and resource-poor settings. Treatment of HIV-TB co-infection is complex and associated with high pill burden, overlapping drug toxicities, risk of immune reconstitution infl ammatory syndrome (IRIS) and challenges related to adherence. From a programmatic point of view, screening of all HIV-infected persons for tuberculosis and vice-versa will help identify co-infected patients who require treatment for both infections. This requires good coordination and communication between the TB and AIDS control programs, in India

Tuberculosis immune reconstitution inflammatory syndrome: profile of an enigmatic condition

Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) in HIV co-infected TB patients is an intriguing but frequently occurring phenomenon experienced by patients after initiating anti retroviral therapy. It is characterized by paradoxical worsening of clinical and radiological manifestations of TB, after initiation of highly active antiretroviral therapy, when improvement in the general condition of the patient is usually anticipated. This paradoxical reaction is brought about by a cascade of inflammatory reactions triggered by the recovery of the immune system both in quality and quantity. Manifestations of TB-IRIS range from mild self-limiting symptoms to life threatening compressive syndromes that could rarely be fatal. Often, this condition is confused with treatment failure or drug toxicity, which could lead to unnecessary drug interruption or substitution. Recognition of this syndrome assumes significance in the context of these two diseases, which mandate prolonged therapy with very high adherence to achieve the desired results. This article provides an overview of the risk factors, pathogenesis, clinical presentation, available diagnostic tools and treatment strategies for TB-IRIS with impli-cations for patients and personnel involved in TB/HIV care

Urine nevirapine as a predictor of antiretroviral adherence

Background & objectives: Incomplete adherence is a major contributor to failure of antiretroviral therapy. Although the available methods to monitor adherence to therapy have proved to be predictive of outcomes, the results are variable. We assessed the feasibility of detecting nevirapine (NVP) in spot urine samples to monitor patient adherence to antiretroviral treatment and to study the urinary excretion of NVP in healthy volunteers after oral administration of a single dose of NVP (200 mg). Methods: Spot urine samples were collected from 50 HIV-infected patients (36 on treatment regimen containing NVP and 14 on drugs other than NVP) and tested for NVP by HPLC in a blinded manner. Sixteen healthy volunteers (9 males and 7 females) were administered a single oral dose of 200 mg NVP and spot urine samples were collected on day ‘0’ before drug administration, and thereafter every 24 h up to 9 days and tested for NVP. Results: All the urine samples collected from patients undergoing treatment with NVP-containing regimens at different time points after drug administration tested positive for NVP. Thirteen out of 14 samples from patients not on NVP yielded a negative result. The drug was detected in the urine of healthy volunteers up to 9 days. The urinary excretion of NVP was prolonged in females than in males. Interpretation & conclusion: In view of its long half-life, NVP gets excreted in urine for a long period of time. Hence, testing spot urine samples for NVP may not be a useful measure to monitor patient adherence to treatment

Clinically meaningful and lasting HbA1c improvement rarely occurs after 5 years of type 1 diabetes: an argument for early, targeted and aggressive intervention following diagnosis.

AIMS/HYPOTHESIS: Our objectives were to explore whether the phenomenon of HbA1c 'tracking' occurs in individuals with type 1 diabetes, how long after diagnosis does tracking take to stabilise, and whether there is an effect of sex and age at diagnosis on tracking. METHODS: A total of 4525 individuals diagnosed with type 1 diabetes between 1 January 1995 and 1 May 2015 were identified from The Health Improvement Network (THIN) database. Mixed models were applied to assess the variability of HbA1c levels over time with random effects on general practices (primary care units) and individuals within practices. RESULTS: 4525 individuals diagnosed with type 1 diabetes were identified in THIN over the study period. The greatest difference in mean HbA1c measurement (-7.0 [95% CI -8.0, -6.1] mmol/mol [0.6%]) was seen when comparing measurements made immediately after diagnosis (0-1 year since diagnosis) with those at 10 or more years (the reference category). The mean difference in HbA1c for the successive periods compared with 10 or more years after diagnosis declined and was no longer statistically significant after 5 years. In the stratified analysis using sex and age group there was considerable heterogeneity with adult onset type 1 diabetes appearing to track earlier and at a lower mean HbA1c. CONCLUSIONS/INTERPRETATION: In individuals with type 1 diabetes, glycaemic control measured by HbA1c settles onto a long-term 'track' and this occurs on average by 5 years following diagnosis. Age at diagnosis modifies both the rate at which individuals settle into their track and the absolute HbA1c tracking level for the next 10 years

CCR2, MCP-1, SDF-1α & DC-SIGN gene polymorphisms in HIV-1 infected patients with & without tuberculosis

Background & Objectives: Variability in the clinical outcome of persons exposed to and infected with HIV-1 and tuberculosis (TB) is determined by multiple factors including host genetic variations. The aim of the present study was to find out whether chemokine, chemokine receptor and DC-SIGN gene polymorphisms were associated with susceptibility or resistance to HIV and HIV-TB in south India. Methods: CCR2 V64I (G/A), monocyte chemoattractant protein-1 (MCP-1) -2518 A/G, stromal cell derived factor-1α; (SDF-1α) 3'UTR G/A and DC-SIGN gene polymorphisms were studied by polymerase chain reaction based methods in HIV-1 infected patients without TB (n=151), with pulmonary TB (PTB) (n=81) and extrapulmonary TB (n=31), 155 PTB patients without HIV and 206 healthy controls. Results: The genotype frequencies of CCR2 V64I, MCP-1 -2518 and DC-SIGN polymorphisms did not differ significantly between the study groups. A significantly increased frequency of GG genotype of SDF-1alpha polymorphism was observed among HIV+PTB+ patients compared to healthy controls (P=0.009, Pc=0.027). Interpretation & Conclusions: Our data suggest that GG genotype of SDF-1alpha 3'UTR polymorphism may be associated with susceptibility to PTB in HIV-1 infected patients. A better understanding of genetic factors that are associated with TB could help target preventive strategies to those HIV patients likely to develop tuberculosis

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

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