Acyclovir and other antivirals such as famciclovir, valacyclovir, foscarnet and val/ganciclovir can all limit acute phase replication and viral shedding. Can use to treat OHL, but will recur without treatment of immunosuppression. Clinical impact of these drugs on HIV-related lymphomas is uncertain.
Limited data suggestive ganciclovir lowers EBV viral load in vivo, especially for PCNSL, but clinical utility undefined.
Comment: The practical and heavily referenced review addresses questions regarding oral lesions in HIV-infected patients. The review includes topical therapies for OHL.
Comment: Seen less frequently nowadays, authors emphasize that OHL can occur in non-HIV settings and also that treatment approaches based on small studies from decades ago and best now handled in the HIV setting through ART.
Comment: HL (which is now the proper term for Hodgkin’s disease) appears to be a group of heterogeneous cancers that have EBV as a factor in at least some of the variants, especially in Africa and lower-resourced countries. HIV is the other virus implicated in the development of HL. EBV is seen more in HL but not in nodular lymphocyte-predominant HL. 60% of classic HL are negative for EBV.
Comment: EBV-related lymphomas in HIV-infected people are heterogeneous. Most are young or middle-aged, and men >> women. Lymphomas of EBV relationship appear to particularly favor the GI tract.
Comment: EBV-related malignancies among the top causes of HIV, along with HHV8 and non-Hodgkin’s lymphoma (NHL). EBV may be the promoter in certain types of Burkitt’s lymphoma (mostly in Africa), NHL (including diffuse large B-cel, extra-nodal natural killer/T-cell nasal type) and nasopharyngeal carcinoma.
Comment: Authors using retrospective data suggest that a cut-off of EBV copies of 200/ml predicted CNS lesions (sensitivity 70-73%, specificity 85-93%) with both PCNSL and AIDS-related lymphoma, respectively. Best specificity was achieved using a cut-off of 2,000 copies.
Comment: Because 4 lymphomas developed during a phase II trial of vicriviroc (a CCR5 antagonist), plasma EBV DNA was monitored in 116 pts who did not experience increases in detectable levels, suggesting that CCR5 antagonism by this drug did not lead to EBV reactivation.
Comment: A thorough overview from an oncologic perspective points out that EBV-driven lymphomas often present with plasmablastic differentiation in HIV+ pts, and that ART appears to improve outcomes with combined chemotherapy protocols.
Comment: Some have questioned the specificity of CSF EBV PCR in Dx of CNS lymphoma in HIV+ pts. This study suggests that the addition of quantitative aspect (namely >10,000 c/ml) improves specificity and positive predictive value compared to qualitative result for Dx of PCNSL (96% vs. 66% and 50% vs. 10%, respectively).
Comment: The article discusses the controversy of whether HIV+ adults have a higher rate of Burkitt’s lymphoma.
Comment: A small study suggests that treatment with ganciclovir, AZT, and IL-2 may have been helpful in 2/5 patients.
Comment: The authors found high rates of EBV (72%) in tested tissues. HIV+ patients also had high rates of HHV-8 seropositivity, but this virus was not associated with tumor cell infection.
Comment: Along with Aboulafia ref, data suggesting that active replication of EBV may be playing role in PCNSL.
Comment: EBV PCR was not helpful diagnostically, but higher EBV PCR viral load correlated with poorer outcomes in the HIV+ population with NHL.
Comment: Case series describing an association.
Comment: Small series refuting claimed high sensitivity/specificity of EBV CSF PCR. Here 26 pts studied with CNS processes, but PCR had only 29% positive predictive value, and specificity 79%. This study more likely reflects real-life statistics in evaluating a diffuse set of CNS conditions in HIV. Authors suggest tests useful for ruling out lymphoma, but Dx requires brain Bx.
Comment: Small RCT of 19 HIV+ pts. examining the use of valacyclovir (with better bioavailability than acyclovir) in the treatment of OHL. Most cases resolved, though in some cases productive EBV replication recurred after discontinuation of treatment. In a few treated cases, treatment failed, which authors attributed to drug-resistant EBV.
Comment: A study of university students in Scotland suggests EBV acquired more frequently in those sexually active. However, since kissing and intercourse are closely related behaviors, it is still unclear whether EBV is commonly acquired by other than salivary shedding.
Comment: The report describes 3 pts suspected of IM with positive heterophile (Monospot) testing who instead had acute HIV infection, with EBV-specific serologies not suggesting acute EBV infection. These cases add to other reports showing that the Monospot can be falsely positive in pts with primary HIV infection.
Comment: A retrospective study examined unselected pts with suspected IM who had negative heterophile antibody tests. 2% had HIV disease by plasma HIV RNA testing. Of those, half had primary HIV infection, and half had chronic HIV disease.
Comment: One of the better papers suggesting the diagnostic utility of CSF EBV DNA PCR in patients with PCNSL. In 136 HIV+ pts with brain lesions, examining both EBV DNA or T. gondii-DNA tests, the positive predictive value for PCNSL increased to >0.96. Regardless, the authors suggested that brain Bx still necessary to establish Dx of PCNSL. However, brain Bx mortality may be ~2%, so this needs to be weighed against risks of inappropriately receiving brain irradiation.
Comment: Report from pre-HAART era suggesting a 60-fold increased risk of NHL in HIV+ pts and linking risks to EBV. From CDC-gathered information, 1686 cases were immunoblastic lymphoma, 548 primary CNS lymphoma, and 590 Burkitt’s lymphoma, a condition not normally associated with immunosuppression.
Comment: An older study from Zambia backs up the perception of the low incidence of infectious mononucleosis in this country, as this serosurvey found minimal evidence of heterophile antibodies.
Comment: OHL described in a subclinical (histopathological) basis in ~17% of HIV+ pediatric patients, which is higher than prior reports in adult populations.
Advanced OHL afflicting lateral tongue margins. This EBV driven process occurs only under immunosuppressive conditions, but can be seen in HIV with CD4 < 500 cells.
Source: CDC/J. S. Greenspan DDS & S. Silverman, Jr. DDS
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