Distribution and determinants of cytomegalovirus induced end organ disease/s among people living with HIV/AIDS in a poor resource setting: observation from India.

BACKGROUND:In India, despite well-established anti-retroviral treatment programs, Cytomegalovirus (CMV) infection-related end-organ diseases (EODs) still remain a major concern resulting in exacerbation of morbidity and mortality among HIV/AIDS patients. A prospective study was designed to understand the distribution and prognosis of CMV associated EODs and to determine a standardized cut-off value for serum CMV viral load associated with the development of EODs amongst HIV/AIDS subjects. METHODS:In a cohort of 400 late-diagnosed HAART naïve HIV/AIDS subjects attending anti-retroviral centers of Kolkata during 2008-2014, the median duration of follow-up was 560 days, and at least 3 visits subsequent to the baseline were mandatory for eligibility. HIV-1 and CMV viral load were estimated by performing Real-Time Polymerase Chain Reactions (PCR). RESULTS:Among subjects, 40.5% (162/400) had CMV EODs which were more common at lower CD4 counts. Poor prognosis and higher death rate were associated with a low CD4 count and increased HIV-1 and CMV viral loads. Subjects having higher CD4 count responded better to therapy [for CD4 = 60-100: Risk Ratio:RR = 1.48 (95% Confidence Interval: 95%CI = 1.18-1.82) and for CD4 = 30-59: RR = 1.64 (95%CI = 1.18-2.27)]. The cut off value of the serum CMV viral load (expressed as log10DNA/ml serum) associated with the development of EODs and disseminated CMV EODs was determined as 5.4 (p<0.0001) and 6.4 (p<0.0001) respectively. These cut offs were found to have satisfactorily high sensitivity, specificity, positive and negative predictive values. CONCLUSION:Prognosis of CMV EOD was poor as indicated by higher death rates among subjects with lower CD4 count, and specific cut-off values were found to have useful potential for identification and treatment of CMV infected HIV/AIDS patients in due time to avoid CMV EODs among HIV/AIDS subjects. Targeted intervention programs seemed to be required urgently to make these cut-offs operational in order to minimize the burden of CMV EOD in this vulnerable population

ROC curve for determining the cut-off value of serum CMV viral load for the development of (i) CMV end organ diseases (EODs) (left) and (ii) Disseminated CMV EODs (right).

<p>ROC curve for determining the cut-off value of serum CMV viral load for the development of (i) CMV end organ diseases (EODs) (left) and (ii) Disseminated CMV EODs (right).</p

Serum CMV viral load amongst the subjects with varying manifestations.

<p>A: All CMV positive subjects (n = 337). B: CMV positive subjects with no CMV associated end-organ diseases (n = 175). C: Subjects with HCMV EODs (n = 162). D: Subjects with HCMV retinitis (n = 58). E: Subjects with HCMV pulmonary diseases (n = 10). F: Subjects with HCMV GIT diseases (n = 19). G: Subjects with disseminated HCMV diseases (n = 75).</p

Association between the prognosis of CMV end organ diseases (EODs) with CD4 count among participating HIV positive patients (N = 400).

<p>Association between the prognosis of CMV end organ diseases (EODs) with CD4 count among participating HIV positive patients (N = 400).</p

Distribution of the baseline characteristics of the participating HIV/AIDS patients (N = 400).

<p>Distribution of the baseline characteristics of the participating HIV/AIDS patients (N = 400).</p

Distribution of serum CMV^* viral load amongst the subjects with varying manifestations.

<p>Distribution of serum CMV^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0117466#t003fn001" target="_blank">*</a>} viral load amongst the subjects with varying manifestations.</p

Distribution and Outcome of CMV End Organ Diseases across the strata of CD4 count among the participating HIV/AIDS patients having CMV EODs (N = 162).

<p>Distribution and Outcome of CMV End Organ Diseases across the strata of CD4 count among the participating HIV/AIDS patients having CMV EODs (N = 162).</p

Sensitivity, specificity, positive and negative predictive values for the CMV viral load cutoffs associated with development and dissemination of CMV associated EODs.

<p>Sensitivity, specificity, positive and negative predictive values for the CMV viral load cutoffs associated with development and dissemination of CMV associated EODs.</p

Limb girdle muscular dystrophy R12 (LGMD 2L, anoctaminopathy) mimicking idiopathic inflammatory myopathy: key points to prevent misdiagnosis.

OBJECTIVES Diagnosing the idiopathic inflammatory myopathies (IIMs) can be challenging as several conditions, including genetic myopathies such as limb girdle muscular dystrophy type R12 (LGMD 2 l, anoctaminopathy), mimic the presentation. Here we describe learning points identified from review of four patients with LGMD 2 l who were initially incorrectly diagnosed with IIM. Our aim is to provide clinicians working in adult rheumatology services with a toolkit to help identify non-inflammatory presentations of myopathy. METHODS We performed retrospective review of medical notes, laboratory results, muscle imaging and histological findings of four patients with LGMD 2 l who were previously misdiagnosed with IIM. We focused on clinical presentation and progression, therapeutic agents used, and events leading to revision of the diagnosis. RESULTS Three males and one female patients with a mean age of 51 years at presentation were reviewed. In each case treatment with immunosuppressants, in one case for >15 years, was observed without a clear therapeutic response. All patients were negative for anti-nuclear antibodies and available myositis-associated/specific autoantibodies and associated connective tissue disease features were absent. Prominent fatty infiltration and selective muscle involvement on thigh muscle magnetic resonance imaging was a common. CONCLUSIONS Adult-onset genetic myopathies, particularly LGMD R12, can mimic IIM. Accurate diagnosis is crucial to avoid use of potentially harmful immunosuppressive therapies, allow appropriate genetic counselling, and facilitate involvement in research studies