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Kaposi sarcoma presenting shortly after primary infection by HIV and human herpesvirus-8

Arranz-Caso, Alberto; Perez-Cruz, Fabiel; Villa, Ana; Sanz, Jose

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doi: 10.1097/QAD.0000000000001690
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Kaposi sarcoma is linked to human herpesvirus-8 (HHV-8), also known as Kaposi sarcoma-associated herpesvirus (KSHV) [1]. Persons living with AIDS have a risk for Kaposi sarcoma 100 000-fold greater than the general population [2,3], particularly MSM, which have a high prevalence of coinfection with KSHV. In these patients, Kaposi sarcoma usually occurs after a long time of coinfection by both viruses and in the presence of severe immunodeficiency [4,5]. We report a patient who presented Kaposi sarcoma shortly after a symptomatic coinfection and viremia by HIV and KSHV and with a well preserved immunity.

A 32-year-old man, bisexual without any other medical history, underwent in April 2010 postexposure prophylaxis following sexual exposure for a month with HAART following a high-risk sexual relationship with an HIV-positive man. Serology for HIV and HHV 6–7–8 were negative at the time, as was the case a year later. In January 2013, he presented with fever and cervical polyadenopathy for 3 weeks and reported having continued to engage in risky sexual practices. ELISA and western blot for HIV were positive, the viral load was 50139 copies/ml and CD4+ cell count was 1154/μl. Histology of cervical lymphadenopathy showed only reactive lymphocytosis. Symptomatic treatment was initiated. Eight weeks later, fever and cervical lymph nodes persisted and he developed a vascular lesion suggestive of Kaposi sarcoma (Fig. 1) alongside the right tonsil. The CD4+ cell count was 880 cells/μl and HIV viral load was 51921 copies/ml. Qualitative PCR for HHV-8 was positive and negative for EBV, CMV and HHV-6–7. Serologies for syphilis, Brucella spp., and Bartonella spp. were negative. Fibroscopy did not reveal other lesions in the oropharynx. Cervico–thoracic–abdominal CT showed numerous cervical, supraclavicular, and bilateral axillary lymphadenopathies. In March 2013, excision biopsy of the pharyngeal lesion was performed along with biopsies of the oropharynx/cavum and a cervical adenopathy. Histology in all biopsies showed infiltration by Kaposi sarcoma with nuclear positivity for HHV-8. HAART was started with raltegravir, tenofovir, and emtricitabine. In July 2013, the fever had resolved, but the lymph nodes persisted and new Kaposi sarcoma lesions appeared in the oropharynx despite of undetectable HIV viral load and 958 CD4+/μl. HHV-8 viral load was also undetectable in blood, whereas serology was then positive. In August 2013, treatment was started with liposomal doxorubicin and dexamethasone which concluded in January 2014. He had a good response with both lymphadenopathy and Kaposi sarcoma lesions disappearing within 2 months. The patient continues in good general condition, with undetectable HIV viral load and 990 CD4+/μl at present (June 2017).

Fig. 1
Fig. 1:
Vascular lesion suggestive of Kaposi sarcoma.

Probably, our patient presented a simultaneous, or very close in time, infection by HIV and KSHV. Shortly after infection, during a KSHV lytic phase, he developed an oropharyngeal Kaposi sarcoma with cervical node involvement. Furthermore, his CD4+ cell count was almost normal. This fact, to our knowledge, has not been communicated previously and opens interesting questions regarding the pathogenesis of Kaposi sarcoma.

HHV-8 is able to produce viral immunomodulators, many of which are homologues of human genes that interfere with the host immune response and confer oncogenic capacity [6,7]. KSHV encodes an interleukin-6 (vIL-6) and three functional chemokines that affect the replication and migration of uninfected cells [8,9]. The vIL-6 activate multiple cellular pathways, including JAK/STAT, which in turn leads to vascular endothelial growth factor expression and signaling [10,11], whereas the chemokines may activate angiogenesis and inhibit the immune type 1 helper-T-cell responses [9]. Similarly, immunodeficiency is thought to play a key role in pathogenesis of Kaposi sarcoma. In HIV patients, a low CD4+ T-lymphocyte cell count and high circulating HIV-1 viral load markedly increase risk of Kaposi sarcoma [9]. Although HAART is helpful in restoring the immune system and reduce HIV viral load, it does not completely prevent the development of Kaposi sarcoma [1,9]. Recently, several studies [12–17] have reported cases of Kaposi sarcoma despite sustained CD4+ cell counts more than 300 cells/μl and suppressed HIV viremia.

In our patient, advanced age, long time of infection, and immunodeficiency, do not play a role. On the contrary, his Kaposi sarcoma appears to be related to early molecular mechanisms of oncogenesis derived from active replication of both viruses. In some cases, especially organ transplant, Kaposi sarcoma can manifest from primary disseminated lytic infection by KSHV [9]. The HIV-1 transactivator protein (Tat) has been hypothesized to contribute to this interplay, although additional factors may also be required [18,19].

As expected, the Kaposi sarcoma of the patient progressed despite achieving undetectable HIV viral load and increased CD4+ cell count after HAART therapy, but responded to chemotherapeutic treatment.

It remains critically important to better understand the HIV/HHV-8 interaction and the triggers that stimulate progression to Kaposi sarcoma.

Acknowledgements

The authors thank Dr Francisco José Vilar (Consultant in Infectious Diseases, Pennine Acute Hospital NHS Trusts) and Dr J. Cuadros (Clinical Microbiology Service, Hospital Príncipe de Asturias, Madrid, Spain) for reviewing the manuscript.

Conflicts of interest

There are no conflicts of interest.

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