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. 2015 Feb 13;10(2):e0117466.
doi: 10.1371/journal.pone.0117466. eCollection 2015.

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

Avirup Chakraborty  1 , Tanmay Mahapatra  2 , Sanchita Mahapatra  2 , Sabbir Ansari  1 , Sattik Siddhanta  3 , Siwalik Banerjee  3 , Dipanjan Banerjee  4 , Rathindra Nath Sarkar  3 , Subhashish Kamal Guha  5 , Nilanjan Chakraborty  1
Affiliations

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

Avirup Chakraborty et al. PLoS One. .

Abstract

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Comparison of death rates between subjects with CMV end organ diseases (EODs) with CD4 counts <30 and 30–59 (following the assumptions of the Cox proportional hazard model and after adjustments for age and gender).
Fig 2
Fig 2. Serum CMV viral load amongst the subjects with varying manifestations.
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).
Fig 3
Fig 3. 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).
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Grants and funding

The current research (Principal Investigator: NC) was funded by the Institutional Intramural Funding of Indian Council of Medical Research, Virus Unit, Government of India (http://icmrvirusunit.org.in/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.