Cedric Spak, M.D.

Ford, E. S., A. S. Magaret, C. W. Spak, S. Selke, S. Kuntz, L. Corey and A. Wald (2018). “Increase in HSV shedding at initiation of antiretroviral therapy and decrease in shedding over time on antiretroviral therapy in HIV and HSV-2 infected persons.” Aids 32(17): 2525-2531.

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OBJECTIVES: HIV-infected persons with chronic herpesvirus infections may experience paradoxical worsening after initiation of antiretroviral therapy (ART), but the impact of longer term ART is unclear. We evaluated the relationships between genital herpes simplex virus (HSV) shedding and ART initiation and time on therapy in HIV and HSV-2-infected persons. DESIGN: Prospective observational study. METHODS: Rates of HSV shedding in 45 HIV and HSV-2-infected persons on or off ART were prospectively followed over up to three, noncontiguous, 60-day periods, during which participants performed daily genital swabs for HSV detection by real-time HSV DNA PCR and reported symptoms. Initiation or discontinuation of ART was at the discretion of participants’ healthcare providers. RESULTS: In all, 6425 daily genital swabs were obtained from 45 persons (38 men and seven women) during 105 swabbing sessions. During the three sessions, 67, 74, and 92% of persons were on ART. HSV was detected on 26.5% of days in men and 22.3% of days in women. The overall rates of genital HSV shedding were 19.4% of days in persons not on ART, 30.2% in persons within 90 days of ART initiation, and 23.3% in persons on ART for longer than 90 days. After initiation of ART, HSV shedding decreased by 2% per month, or 23% per year (RR 0.98/month on ART; P = 0.0003 in adjusted analysis). This finding was consistent after including consideration of HIV viral load and CD4 cell count. CONCLUSIONS: HSV shedding increased significantly shortly after ART initiation, but decreased with time on prolonged ART.

Soape, M. P., R. S. Rahimi, C. W. Spak and J. F. Trotter (2018). “Case Report of a Rare Presentation of Isolated Cytomegalovirus Hepatitis After Renal Transplantation.” Prog Transplant 28(3): 296-298.

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Although CMV infection and disease are recognized complications of renal transplant, CMV hepatitis is distinctly uncommon. A recent study showed kidney transplant recipients receiving CMV prophylaxis, and CMV disease incidence was 19.2%. Thus, CMV disease was not surprising in this case, given the multiple risk factors. Thymoglobulin induction alone increased the risk of CMV infection by 4 times. With these risk factors, the transplanted kidney was uncharacteristically spared. Our case reemphasizes the significance for CMV prophylaxis, which was not optimized with our patient, and stopping valganciclovir certainly contributed to disease progression. Prophylaxis is defined as administration of antiviral agents at the onset of the transplantation. Our institutional protocol outlines the prophylactic use of valganciclovir in all liver and kidney transplantations. Another form of preventive CMV therapy is preemptive, which involves periodic monitoring of viremia to allow for prompt treatment. It has been shown that any form of preventive treatment for any CMV serology status has decreased CMV-associated mortality, all-cause mortality, and clinically important diseases due to opportunistic infections. To our knowledge, it has been 20 years since an isolated CMV hepatitis in renal transplantation was reported in the United States and none since the advent of current CMV prophylaxis regimens. In conclusion, this case illustrates the importance of CMV prophylaxis while presenting a rare case of isolated CMV hepatitis. (Excerpt from text, p. 298; no abstract available.)

Singh, N., C. D. Sifri, F. P. Silveira, R. Miller, K. S. Gregg, S. Huprikar, E. D. Lease, A. Zimmer, J. S. Dummer, C. W. Spak, C. Koval, D. B. Banach, M. Shroff, J. Le, D. Ostrander, R. Avery, A. Eid, R. R. Razonable, J. Montero, E. Blumberg, A. Alynbiawi, M. I. Morris, H. B. Randall, G. Alangaden, J. Tessier, T. V. Cacciarelli, M. M. Wagener and H. Y. Sun (2016). “Unique characteristics of cryptococcosis identified after death in patients with liver cirrhosis: Comparison with concurrent cohort diagnosed antemortem.” Med Mycol: 2016 Sep [Epub ahead of print].

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Characteristics of cirrhosis-associated cryptococcosis first diagnosed after death are not fully known. In a multicenter study, data generated as standard of care was systematically collected in 113 consecutive patients with cirrhosis and cryptococcosis followed for 80 patient-years. The diagnosis of cryptococcosis was first established after death in 15.9% (18/113) of the patients. Compared to cases diagnosed while alive, these patients had higher MELD score (33 vs. 22, P = .029) and higher rate of cryptococcemia (75.0% vs. 41.9%, P = .027). Cases diagnosed after death, in comparison to those diagnosed during life were more likely to present with shock (OR 3.42, 95% CI 1.18-9.90, P = .023), require mechanical ventilation at admission (OR 8.5, 95% CI 2.74-26.38, P = .001), less likely to undergo testing for serum cryptococcal antigen (OR 0.07, 95% CI 0.02-0.21, P < .001) and have positive antigen when the test was performed (OR 0.07, 95% CI 0.01-0.60, P = .016). In a subset of cirrhotic patients with advanced liver disease cryptococcosis was first recognized after death. These patients had the characteristics of presenting with fulminant fungemia, were less likely to have positive serum cryptococcal antigen and posed a diagnostic challenge for care providers.