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New developments in the treatment of opportunistic infections
Course C2. AIDS and STD viruses, such as persistent and ulcerating herpes, generalized zoster or disseminated mollusca contagiosa were diagnosed in about 10% of our patients before and in less than 2% since the introduction of HAART. Similarly, oral hairy leukoplakia was mostly observed in patients without combination therapy. Even more surprising was the effect on newly appearing Kaposi sarcoma (KS): In 10 patients HAART was initiated for KS and in 6 of them KS disappeared without any further treatment. As HAART had no effect on the frequency of condylomata acuminata or verrucae vulgares, it remains to be questioned whether HAART had a direct or indirect effect on KS-growth. A similar observation suggests a subtle effect of HAART on oral candidiasis: although the frequency of oral candidiasis remained unchanged, pseudomembranous or erosive candidiasis was no longer observed. Although HIV-associated infectious diseases were strongly reduced, the manifestation of non infectious skin diseases like psoriasis, seborrhoic dermatitis or prurigo-like dermatitis seemed to be unchanged. New drug induced diseases, such as papular exanthema or “buffalo-hump” are encountered more frequently. However, most of these side effects are easily managed and the risk-benefit-ratio is clearly in favour of HAART.
IC2-9
s45
HHVI:,A new sexually transmitted disease
C. LebbC. Department of Dermatology, Hepita Saint-Louis, Paris, France A new gamma herpesvirus called human herpesvirus 8 (HHVS) was discovered using representational differential analysis in 1994. HHVS has been associated with Kaposi’s sarcoma, primary effision lymphoma and multicentric Castleman’s disease. Whether HI-IV8 is an ubiquitous or a restricted virus remains controversial. Seroprevalence depends on geographical origin and technical considerations. Sero-epidemiological studies from Western countries, mostly from HIV infected subjects and from HIV negative people at very high risk for sexually transmitted diseases, show that HHVS is sexually transmitted while transmission by blood products, although theoretically possible, is not a frequent event. By contrast, few data concerning HIV negative subjects are available concerning HHV8 sexual transmission. Furtbermore, data from countries where HI-IV8 seroprevalence is high suggest that the virus is generally transmitted before puberty.
C2-10 Current trends in antiretroviral therapy I C2-8 New developments
opportunistic
in the treatment of infections
Uhich R. Hengge. Department of Dermatology and Venereology, University of Essen, Germany Besides the progress in antiretroviral and immunotherapy pf HIV infection, the treatment of opportunistic infections has been greatly improved in the last couple of years. On the one hand, prophylactic treatment of oral candidosis can be omitted when appropriate increases of CD4 cell counts have occurred following highly active antiretroviral therapy (HAART). Moreover, patients suffering from cytomegalovirus retinitis are increasingly receiving less frequent maintenance therapy once their CD4 counts have augmented following the institution of HAART. The arrival of liposomally-encapsulated anthncyclines has improved the treatment of Kaposi’s sarcoma. By encapsulation of doxorubicin and daunorubicin in liposomes, a selective enrichment of the active drug, can be achieved through extravasation in fenestrated endothelia. Moreover, the half life has been considerably prolonged up to 20 hours leading to improved response of the tumor. We have treated a total of 70 patients, some of which achieved a clinical and vitological complete response. The side effect profile of antbracyclin has been less toxic despite high cumulative doses as compared to conventional treatment. The arrival of cidofovir has provided the physicians with an antiviral drug, which is effective against a variety of herpesviruses such as CMV, HSV-1 and 2, EBV as well as against papillomavirus, poxviruses and Jakob-Creutzfeld virus. Cidofovir has recently also been applied topically in a 5% gel. Imiquimod represents an immunomodulating drug, which is currently licensed for the treatment of condylomata acuminata. However, it is also in clinical trials for other applications. Other new therapeutic options for the treatment of herpes zoster, hepatitis B and C will be presented. New diagnostic means such as the quantification of multiple herpes viruses e.g. cytomegalovirus have enabled the development of preemptive treatment strategies.
A. Rieger. DIAID. Department of Dermatology, University of Vienna Medical School, Henna, Austria Protease inhibitor containing regimens, termed highly active antiretroviral therapy (HAART) have been associated with a massive decrease in AIDS-associated morbidity and mortality. Incidence rate reductions of over 70% in certain opportunistic diseases (eg. CMV chorioretinitis) have been reported. In case of ongoing opportunistic conditions such as cryptosporidiosis, Kaposi sarcoma and molluscum contagiosum, improvements or resolutions have been described. In terms of maximal suppression of viral replication, approximately 50% of patients respond to HAART. Although the clinical benefit of HAART has been demonstrated only in advanced patients, our current pathogenetic concept of this infection favors early treatment of all HIV-infected patients. However HAART is complex, pharmacological vulnerable, and we are just beginning to identify long-term side effects of protease inhibitors. ElC2 11 Skin manifestations in HIV-infected children Christine Bodemer. Paris, France The dermatologists must be aware of the cutaneous lesions seen in children with AIDS or AIDS-related complex: - to institute rapid and early treatment; - and because these cutaneous manifestations may be the early, warning signs of undiagnosed cases of paediatric AIDS No cutaneous manifestations appeared specific of paediatric AIDS. The most common cutaneous findings are those associated with infections, which tend to be less responsive to conventional therapies thnn in the healthy child. Recalcitmnt candidasis are extremely common with persistant candid&s in the diaper area, or oral candidasis. Occasionnaly superficial fungal infections are observed, with sometimes unusual morphologies. Bacterial infections of the skin am especially common in pediatric AIDS, particularely cellulitis, impetigo, recurrent folliculitis, usually due to staphylococcus aureus. I&
IC2-9
s45
HHVI:,A new sexually transmitted disease
C. LebbC. Department of Dermatology, Hepita Saint-Louis, Paris, France A new gamma herpesvirus called human herpesvirus 8 (HHVS) was discovered using representational differential analysis in 1994. HHVS has been associated with Kaposi’s sarcoma, primary effision lymphoma and multicentric Castleman’s disease. Whether HI-IV8 is an ubiquitous or a restricted virus remains controversial. Seroprevalence depends on geographical origin and technical considerations. Sero-epidemiological studies from Western countries, mostly from HIV infected subjects and from HIV negative people at very high risk for sexually transmitted diseases, show that HHVS is sexually transmitted while transmission by blood products, although theoretically possible, is not a frequent event. By contrast, few data concerning HIV negative subjects are available concerning HHV8 sexual transmission. Furtbermore, data from countries where HI-IV8 seroprevalence is high suggest that the virus is generally transmitted before puberty.
C2-10 Current trends in antiretroviral therapy I C2-8 New developments
opportunistic
in the treatment of infections
Uhich R. Hengge. Department of Dermatology and Venereology, University of Essen, Germany Besides the progress in antiretroviral and immunotherapy pf HIV infection, the treatment of opportunistic infections has been greatly improved in the last couple of years. On the one hand, prophylactic treatment of oral candidosis can be omitted when appropriate increases of CD4 cell counts have occurred following highly active antiretroviral therapy (HAART). Moreover, patients suffering from cytomegalovirus retinitis are increasingly receiving less frequent maintenance therapy once their CD4 counts have augmented following the institution of HAART. The arrival of liposomally-encapsulated anthncyclines has improved the treatment of Kaposi’s sarcoma. By encapsulation of doxorubicin and daunorubicin in liposomes, a selective enrichment of the active drug, can be achieved through extravasation in fenestrated endothelia. Moreover, the half life has been considerably prolonged up to 20 hours leading to improved response of the tumor. We have treated a total of 70 patients, some of which achieved a clinical and vitological complete response. The side effect profile of antbracyclin has been less toxic despite high cumulative doses as compared to conventional treatment. The arrival of cidofovir has provided the physicians with an antiviral drug, which is effective against a variety of herpesviruses such as CMV, HSV-1 and 2, EBV as well as against papillomavirus, poxviruses and Jakob-Creutzfeld virus. Cidofovir has recently also been applied topically in a 5% gel. Imiquimod represents an immunomodulating drug, which is currently licensed for the treatment of condylomata acuminata. However, it is also in clinical trials for other applications. Other new therapeutic options for the treatment of herpes zoster, hepatitis B and C will be presented. New diagnostic means such as the quantification of multiple herpes viruses e.g. cytomegalovirus have enabled the development of preemptive treatment strategies.
A. Rieger. DIAID. Department of Dermatology, University of Vienna Medical School, Henna, Austria Protease inhibitor containing regimens, termed highly active antiretroviral therapy (HAART) have been associated with a massive decrease in AIDS-associated morbidity and mortality. Incidence rate reductions of over 70% in certain opportunistic diseases (eg. CMV chorioretinitis) have been reported. In case of ongoing opportunistic conditions such as cryptosporidiosis, Kaposi sarcoma and molluscum contagiosum, improvements or resolutions have been described. In terms of maximal suppression of viral replication, approximately 50% of patients respond to HAART. Although the clinical benefit of HAART has been demonstrated only in advanced patients, our current pathogenetic concept of this infection favors early treatment of all HIV-infected patients. However HAART is complex, pharmacological vulnerable, and we are just beginning to identify long-term side effects of protease inhibitors. ElC2 11 Skin manifestations in HIV-infected children Christine Bodemer. Paris, France The dermatologists must be aware of the cutaneous lesions seen in children with AIDS or AIDS-related complex: - to institute rapid and early treatment; - and because these cutaneous manifestations may be the early, warning signs of undiagnosed cases of paediatric AIDS No cutaneous manifestations appeared specific of paediatric AIDS. The most common cutaneous findings are those associated with infections, which tend to be less responsive to conventional therapies thnn in the healthy child. Recalcitmnt candidasis are extremely common with persistant candid&s in the diaper area, or oral candidasis. Occasionnaly superficial fungal infections are observed, with sometimes unusual morphologies. Bacterial infections of the skin am especially common in pediatric AIDS, particularely cellulitis, impetigo, recurrent folliculitis, usually due to staphylococcus aureus. I&