HIV-Associated Kaposi's Sarcoma with a High CD4 Count and a Low Viral Load

Maurer, Toby; Ponte, Maya; Leslie, Kieron

doi:10.1056/nejmc070508

Cited by 190 publications

(140 citation statements)

References 4 publications

Supporting

Mentioning

126

Contrasting

Unclassified

Order By: Relevance

“…Ten KS cases arose in PWHA whose CD4 cell count was very low despite concurrent HAART use whereas 5 MSM developed KS despite being on HAART and having CD4 cell counts at which AIDS-related KS is seldom seen (Biggar et al, 2007). The occurrence of KS cases in PWHA with high CD4 cell counts and undetectable viral loads has already been reported in the United States after 1996 (Maurer et al, 2007;Krown et al, 2008). It is possible that, with the ageing of PWHA, those who are co-infected with KS herpesvirus may develop KS despite good control of HIV infection.…”

Section: Discussionmentioning

confidence: 97%

Kaposi sarcoma incidence in the Swiss HIV Cohort Study before and after highly active antiretroviral therapy

et al. 2008

View full text Add to dashboard Cite

Between 1984 and 2006, 12 959 people with HIV/AIDS (PWHA) in the Swiss HIV Cohort Study contributed a total of 73 412 person-years (py) of follow-up, 35 551 of which derived from PWHA treated with highly active antiretroviral therapy (HAART). Five hundred and ninety-seven incident Kaposi sarcoma (KS) cases were identified of whom 52 were among HAART users. Cox regression was used to estimate hazard ratios (HR) and corresponding 95% confidence intervals (CI). Kaposi sarcoma incidence fell abruptly in 1996 -1998 to reach a plateau at 1.4 per 1000 py afterwards. Men having sex with men and birth in Africa or the Middle East were associated with KS in both non-users and users of HAART but the risk pattern by CD4 cell count differed. Only very low CD4 cell count (o50 cells ml À1 ) at enrolment or at HAART initiation were significantly associated with KS among HAART users. The HR for KS declined steeply in the first months after HAART initiation and continued to be low 7 -10 years afterwards (HR, 0.06; 95% CI, 0.02 -0.17). Thirty-three out of 52 (63.5%) KS cases among HAART users arose among PWHA who had stopped treatment or used HAART for less than 6 months.

show abstract

Section: Discussionmentioning

confidence: 97%

Kaposi sarcoma incidence in the Swiss HIV Cohort Study before and after highly active antiretroviral therapy

et al. 2008

View full text Add to dashboard Cite

show abstract

“…This strategy, that allows immune rescue and Human immunodeficiency virus (HIV) replication control, frequently leads to clinical regression of most KS lesions without the need for specific chemotherapies (Sgadari et al, 2002;Monini et al, 2009). However, although KS tends to decline upon antiretroviral treatment, paradoxical aggravations have been described during the early treatment period, where recovery is generally slow (Mitsuyasu, 2000;Maurer et al, 2007). Recurrence has also been observed in longterm treated aging patients.…”

Section: Introductionmentioning

confidence: 99%

Remodeling of VE-cadherin junctions by the human herpes virus 8 G-protein coupled receptor

et al. 2010

View full text Add to dashboard Cite

Kaposi Sarcoma (KS) are opportunistic tumors, associated with human herpes virus 8 (HHV8) infection. KS development is highly favored by immune-depression and remains the second most frequent tumor in acquired immune deficiency syndrome patients. Although it has been shown that experimental expression of the HHV8 G-proteincoupled receptor (vGPCR) in the endothelial compartment is alone sufficient to recapitulate the formation and progression of KS-like lesions, its functional effects on endothelial homeostasis are not fully understood. Here we show that vGPCR expression in endothelial cells induces an increase in paracellular permeability both in vivo and in vitro. By using pharmacological inhibitors and small interference RNA-based knockdown, we demonstrate an essential role for the PI(3)Kinase-c/Rac nexus in vGPCRmediated permeability. This was further accompanied by dramatic remodeling of VE-cadherin-dependent cell-cell junctions. Importantly, this in vitro vGPCR-initiated signaling signature was observed in a large panel of human KS. Altogether, our results support the hypothesis that endothelial vGPCR signaling is co-opted in KS, and unveil new key cellular targets for therapeutic intervention.

show abstract

“…However, new-onset or unremitting ks has been reported in hiv-infected patients with an undetectable viral load and restored CD4+ T-cell count. In 1999, the first 2 cases of hiv-ks in the setting of viral suppression were reported by Chan et al 5 , followed by several case series of hiv-ks with CD4+ T-cell counts exceeding 300/μL and an undetectable hiv viral load 6,7 . Still, ks persistence despite effective art remains rare.…”

Section: Hiv-ks In the Context Of Virus-controlled Hiv Infectionmentioning

confidence: 99%

“…Factors that have been postulated to play a role in the development or persistence of ks in such patients include older patient age, duration of hiv infection, and type of art used 6,8 . More recently, Unemori et al observed that increased frequencies of immunosenescence phenotypes (CD57+ and CD28−) and lower frequencies of naïve T cells (CD27+, CD28+, CD45RA+) are associated with the presence of ks in art-treated patients, indicating a role for "immune aging" in relation to an increasing vulnerability to ks 9 .…”

Section: Hiv-ks In the Context Of Virus-controlled Hiv Infectionmentioning

confidence: 99%

Imatinib for Highly Chemoresistant Kaposi Sarcoma in a Patient with Long-Term HIV Control: A Case Report and Literature Review

et al. 2015

View full text Add to dashboard Cite

Kaposi sarcoma (ks) is a vascular tumour caused by oncogenic human herpesvirus type 8; it often occurs with hiv-associated immunosuppression. Numerous cellular signalling pathways are involved in the pathogenesis of ks, among which receptor tyrosine kinases such as the c-Kit and platelet-derived growth factor receptors play an important role. Imatinib mesylate, a tyrosine kinase inhibitor, has resulted in partial regression of ks lesions in one third of treated patients, but its mechanism of action remains unclear.Here, we report the case of a white man with recurrent ks despite well-suppressed hiv infection and multiple chemotherapies who received imatinib and showed a complete and sustained tumour response. To our knowledge, this report is the first showing the value of imatinib in the management of ks in the context of long-lasting hiv control with adequate quantitative CD4 recovery. Our case indicates that imatinib can be a treatment option for highly chemoresistant recurrent ks in patients on long-term antiretroviral therapy.

show abstract

HIV-Associated Kaposi's Sarcoma with a High CD4 Count and a Low Viral Load

Cited by 190 publications

References 4 publications

Kaposi sarcoma incidence in the Swiss HIV Cohort Study before and after highly active antiretroviral therapy

Kaposi sarcoma incidence in the Swiss HIV Cohort Study before and after highly active antiretroviral therapy

Remodeling of VE-cadherin junctions by the human herpes virus 8 G-protein coupled receptor

Imatinib for Highly Chemoresistant Kaposi Sarcoma in a Patient with Long-Term HIV Control: A Case Report and Literature Review

Contact Info

Product

Resources

About