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Hybridization experiments indicated substantial differences between the genomes of HIV-1 and HIV-2 purchase vermox line hiv infection by country. Serological cross-reactivity was restricted to the major core protein purchase discount vermox on-line hiv infection rates msm, as the envelope glycoproteins of HIV-2 are not immunoprecipitated by HIV-1- positive sera (Clavel 1986) best purchase vermox hiv infection statistics us. HIV-2 bears all the hallmarks of a lentivirus but is more closely related to simian immunodeficiency viruses (SIV) than HIV-1, despite a similar biology (Clavel 1986, Kanki 1986). Whereas HIV-1 in humans resulted from at least four cross-species trans- missions of SIVs from chimpanzees and gorillas in West Central Africa, HIV-2 resulted from at least nine independent transmissions of SIVs infecting sooty mangabeys in West Africa only There are at least nine different HIV-2 subtypes. The most preva- lent HIV-2 subtype is A (Senegal, Gambia, Guinea-Bissau, Cape Verde Islands, Ghana, Ivory Coast), followed by B (Ghana, Ivory Coast). Others subtypes (C-I) are rarely seen and are seemingly dead-end transmissions (Peeters 2014). A reduced rate of clinical progression indicates that HIV-2 has a reduced virulence compared to HIV-1 (Marlink 1994). However, there are several diagnostic, clinical and therapeutic challenges with HIV-2 infection to be discussed in this chapter. Epidemiology HIV-2 infection is endemic in West Africa. An estimated 1 to 2 million people in this region are infected with HIV-2. The proportion of HIV-2 among new HIV infections worldwide is estimated to be 0. However, in recent years HIV-2 prevalence has declined markedly. The lower transmission rates of HIV-2 are probably due to its lower viremia in infected individuals. For example, in a rural area like Guinea-Bissau, a region with one of the highest numbers of HIV-2 infections worldwide, prevalence declined from 8. During the same period HIV-1 preva- lence increased from 0. HIV-2 infection has also been reported in countries with historical and socio-eco- nomic ties to West Africa, among them mainly Portugal (2008: 1813 cumulative cases), but also France (2008: 572 cases in the ANRS cohort, 2% of all new infec- tions), Spain (2013: 297 cases), Great Britain (2010: 137 cases), USA, India and Korea (Carvalho 2010, Drylewicz 2008, de Mendoza 2014, Gilleece 2010). Diagnosis Generally, Western Blot analysis leads to definite discrimination between an HIV-1 or HIV-2 infection (see Chapter Test). However, it may be difficult to distinguish between mono- and dual infection. Due to the close relationship cross-reactivity 514 Other Infections than HIV-1 leading to antibody reactions against both virus types can occur. There are no commercial PCR tests available, but some labs offer in-house tests. Viremia levels are usually lower than those seen with HIV-1 (see below), the detection limit is usually 100 copies/ml. HIV-2 testing is strongly recommended in all patients (especially those from West African countries), showing HIV-associated or AIDS-defining illnesses (and/or low CD4 T cells) in the presence of low or undetectable HIV-1 viremia and/or an indeterminate or nonreactive HIV-1 Western Blot. Natural Course In general, there are no differences between HIV-2 and HIV-1 with regard to the clinical manifestation. If left untreated, HIV-2-infected patients with low CD4 T cells develop illnesses similar to those seen in HIV-1-infected patients. Almost all AIDS- defining infections and malignancies have been seen in HIV-2-infected patients. Given the endemic setting of HIV-2, some AIDS events such as TB, wasting syndrome and chronic diarrhea may be seen more frequently (Markovitz 1994, Ndour 2000, Matheron 2003). As HIV-1, HIV-2 is a neurotropic virus and can be isolated from cerebrospinal fluid in some patients (Arvidson 2004). A reduced rate of clinical progression indicates that HIV-2 has a reduced virulence compared to HIV-1. The asymptomatic incubation period after infection with HIV- 2 appears to be substantially longer. In a prospective clinical study on HIV+ woman from 1985 to 1993, HIV-1-infected women had a 67% probability of AIDS-free sur- vival 5 years after seroconversion in contrast with 100% for HIV-2-infected women (Marlink 1994). So-called long-term non-progressors (LTNPs) and elite controllers (undetectable viral load in the absence of ARVs) are seen much more frequently than in HIV-1-infected patients (Marlink 1994, Hansmann 2005). Among 342 HIV-2- infected patients of a French HIV-2 cohort, the prevalence of LTNPs (i. Most LTNPs (81%) were elite controllers, whereas only 55% of HIV controllers were LTNPs (Thiebault 2011). HIV-2 viremia levels are much lower than those of HIV-1. In several studies, the median viral load was 30-100 fold lower, irrespective of the length of time infected or disease stage (Andersson 2000, Popper 2000, Hansmann 2005). A high viral load can already be considered when the HIV-2 RNA copy number is above 1,000/ml (Gilleece 2010). In total, mortality in patients with an undetectable viremia (<100 copies/ml) seems to be similar to that of the general population (van der Loeff 2010). However, there are also some patients showing clinical progression with low viremia or even with an absence of detectable viremia (Soares 2011, Hegedus 2014), impli- cating a dichotomy between amount of plasma virus and cell-associated viral burden. In general, CD4 T cells in HIV-2 infected patients are higher than in patients with HIV-1. Clinical progression mainly depends on plasma viremia and can be seen even at high CD4 stages (Sousa 2002, Hansmann 2005, van der Loeff 2010, Hegedus 2014). The main transmission routes of HIV-2 are sexual contacts, needle sharing, perina- tal infections or blood products. The heterosexual spread of HIV-2 is significantly slower (3-9 fold) than that of HIV-1, which strongly suggests differences in the viruses’ infectivity potential (Marlink 1994, Gilbert 2003). This may be due to the fact that HIV-2 levels are lower not only in plasma but also in the semen and in the female genital tract (Gottlieb 2006, Raugi 2013). In addition, the rates of mother-to-child transmission (MCT) of HIV-2 is lower compared to HIV-1. In a study from The Gambia HIV-2 Infection 515 that enrolled 144 pregnant women positive for HIV-1 and 294 for HIV-2, the esti- mated transmission rate of HIV-1 was 24. In a French cohort of 223 pregnant women, the mother-to-child transmission rate for HIV-2 was only 0. Pathogenesis Is HIV-2 a model for a possible host control of HIV infection? Current data suggest that both factors are involved. Several differences between HIV-2 and HIV-1 infection are evident: • Viral replication (plasma RNA, intracellular mRNA) • Level of immune activation • Response of the adaptive immune system (T cells and neutralizing antibodies), • Activity of the innate immunity • Activity and functions of viral proteins In a French cohort of untreated patients (320 cases with HIV-1 and 160 with HIV- 2), CD4 T cell counts decreased less rapidly in HIV-2 than in HIV-1 patients. The decline was -9 versus -49 cells/µl per year (Drylewicz 2008).
Rather than chrono- conditions and begin treatment after the age of 70 cheap vermox 100 mg with visa hiv infection rates louisiana. Life expectancy in the United States17 The number and severity of comorbid health conditions also provides Life expectancy buy generic vermox 100mg online kleenex anti viral 112, y important information regarding patient ﬁtness vermox 100mg with mastercard hiv infection rates manchester. A Mayo Clinic study of 373 unselected CLL patients found that 89% of newly diagnosed Current age, y Men Women patients had at least one comorbid condition and 46% had at least one 65 18. Although the presence of a major comorbidity affected OS on univariate analysis, it was not a signiﬁcant predictor on the multivariate analysis adjusting for CLL-speciﬁc characteristics (eg, and the pharmacokinetics (absorption, metabolism, excretion) of the 20 stage). This ﬁnding underscores that CLL-related characteristics are drugs to be used become key considerations in evaluating the suitability of a given treatment approach. This principle is well often the major factor inﬂuencing survival even when substantial illustrated by the Cancer and Leukemia Group B (CALGB) 9011 comorbidities are present. Although it enrolled only ﬁt older patients trial, which found that creatinine clearance rather than age was the (performance status 0-2, no severe organ disfunction), the presence of 2 primary predictor of higher toxicity with ﬂudarabine-based therapy or more comorbid health conditions was still associated with shorter 18 PFS and shorter OS in the German CLL5 trial. Historically, trials have primarily used an exclusionary (rather than a stratiﬁcation) approach declaring patients above an age cutoff Organ function is a third factor in assessing patients’ suitability for or with any decrease in organ function or performance status aggressive treatment. It is well recognized that renal function decreases 19 with age. These criteria have excluded those with the characteristics typical of real-world CLL patients from participating. A consistent approach Renal Disease (MDRD) equation. For the patient they are evaluating and facilitate more rapid translation of example, a study of 100 000 individuals from Japan found that trial results into routine clinical practice. Although patients were traditionally classiﬁed based on age alone, it is now well recognized that chronologic age is not a reliable surrogate for physiologic age or ﬁtness. Measuring only one of these dimensions can lead to an inaccurate assessment of overall patient ﬁtness. CGA includes most widely used assessment of patient ﬁtness in oncology practice, evaluation of function, coexisting health problems, level of social has a moderate correlation with more formal CGA instruments,32 it support, cognitive ability, nutritional status, and common syndromes is an inadequate measure of function for most older adults. Given the assessments have been shown to reliably predict the ability of elderly importance of assessing ﬁtness/frailty in the management of CLL patients to tolerate chemotherapy in other malignancies. Selected standardized tools to evaluate various dimensions of patient ﬁtness CGA and functional assessment Comorbidities Quality of life 101 27 Activity of Daily Living (ADL) CIRS-G European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30102 Instrument of Activities of Daily Living (AIDL)103,104 Charlson Comorbidity Index28 Functional assessment of cancer therapy-general (FACT-G)105 ECOG performance status106 Adult Comorbidity Evaluation (ACE-27)107 Patient Reported Outcome Measurement Information System (PROMIS)108 Others26 Others109 Hematology 2013 159 launched an international initiative to bring greater consistency to this Table 3. Supportive care considerations for CLL patients assessment. It is hoped that this effort will identify standard criteria by Suggestions which both ﬁt and less ﬁt CLL patients may be selected for trials and that can be used to stratify patients within a trial to evaluate how ﬁtness Cancer screening ● Whole-body skin examination annually. This effort will also explore how such ● Age-appropriate screening for breast, criteria may be used to inform therapy selection in routine clinical practice. Vaccination strategies54 ● Prevnar 13 pneumococcal vaccination The indications to initiate therapy for elderly patients with CLL are should be given at diagnosis followed 8 generally the same as those for younger patients. Up to 50% of older patients have been found to have ● Annual inﬂuenza vaccination should be depression,34,36 and patients should be speciﬁcally screened for depres- given. Although a lymphocyte doubling time of less than 6 months is live attenuated typhoid vaccines. CLL experts appear to have a greater tolerance for delaying older adults. Because Consider evaluation of vitamin D levels treatment increases rather than decreases the risk of infection, because this recommendation frequent or recurrent infections are also not a reason to initiate increases risk of vitamin D deﬁciency. Studies from both the United mended, live attenuated vaccines, including Zostavax, are contra- States and Italy suggest that low vitamin D levels may be associated indicated in patients with CLL (Table 3). Nonetheless, vitamin D assess- is limited information on the utility of these molecular biomarkers ment in patients at risk can be considered good general care for elderly for predicting outcome in older CLL patients. In Center for Disease Control vaccination guidelines (updated in contrast, prognostic testing had minimal to no value for predicting 2012) suggest that all immunocompromised patients, such as OS among patients age 75 after adjusting for stage. Determining the goals of treatment for older patients with CLL. The combination of performance status, comorbidity assessment, CGA (such as independence with activities of daily living), and organ function (primarily creatinine clearance) are more How to select therapy for older patients important factors than age in determining treatment goals. In younger patients without comorbidities, genetic characteristics of the clonal B cells (del[17p13], TP53 gene mutations, del[11q23]) are the In patients with a long life expectancy unrelated to CLL and good primary factor inﬂuencing therapy selection. Deep remission (even 57 functional status, deep remission remains an appropriate goal minimal residual disease–negative remission) is the goal of treatment regardless of age. For those with short life expectancy due to other and the treatment strategies offering the best PFS and OS should be 8,58-64 health conditions, palliation is appropriate. Based on a series of phase 3 trials, most patients (with 8 CLL fall somewhere in between and require that clinicians balance a exception of those having TP53 defects) should receive an FCR or 65,66 variety of considerations when selecting therapy. The German CLL Study Group mind that, with the exception of allogeneic stem cell transplantation, (GCLLSG) CLL10 trial will determine whether bendamustine and 67 the current treatments for CLL are noncurative. Although achieving the rituximab (BR) is an acceptable alternative in these patients. Inclusion longest remission duration possible is an appropriate strategy in of an alkylating agent appears to be important for patients with deletion 68 younger patients, intermediate durations of remission (eg, 3-4 years) 11q23. Although associated with PFS, this cytogenetic defect does with salvage therapy at relapse may be more appropriate for some not appear to effect OS when these patients are treated with FCR-like 69 elderly patients if this approach offers less toxicity and better quality of platforms. As outlined in the accompanying chapter in this publica- 70 life. Selecting a too aggressive approach that requires extensive dose tion by Gribben and Riches, suitable young patients with del(17p13) reduction or results in discontinuation of treatment may be less in need of treatment should be debulked and proceed to reduced 71,72 beneﬁcial than choosing a better tolerated treatment that allows intensity allogeneic stem cell transplantation. As discussed, the selection of therapy in older patients is more complex because they are more likely to have coexistent health Which therapy is best (for this patient)? Establishing the goals of treatment is the ﬁrst step in and greater than half have at least one major comorbidity under- therapy selection (Figure 1). Patient characteristics (rather than the scores that therapy selection must be individualized. The tight link between efﬁcacy and toxicity with historical CLL therapy. This ﬁgure is a summary illustrating the link between efﬁcacy and toxicity with historical CLL treatments. It cannot be used to compare regimens directly because results are drawn from across trials with different patient characteristics. In some cases, multiple trials testing the same regimen found slightly different PFS and rates of grade 3/4 toxicity; the representative experience is indicated in such cases. After determining the goals of treatment, the higher proportion of patients in the chlorambucil arm discontinued best strategy to achieve these goals must be determined. Greater improvements in characteristics of the treatment regimen (efﬁcacy, toxicity, mecha- quality of life were observed in the ﬂudarabine arm at both 6 and 12 nism drug elimination/metabolism) and the patient’s underlying months. Although no difference in OS was observed, interpreting organ function become substantial considerations.
Psoriatic Arthritis in Children No evidence on the comparative effectiveness of targeted immune modulators for the treatment of psoriatic arthritis in children exists purchase vermox once a day hiv infection rates per country. In addition purchase vermox overnight delivery hiv infection rate country, no placebo-controlled trials on children with psoriatic arthritis are evident in the literature purchase vermox overnight hiv infection early stages. Crohn’s Disease The following drugs are currently approved by the US Food and Drug Administration for the treatment of Crohn’s disease: adalimumab, certolizumab pegol, infliximab, and natalizumab. Summary of findings Overall, the strength of evidence on the comparative effectiveness of targeted immune modulators for the treatment of Crohn’s disease was insufficient (Table 13). We did not find any Targeted immune modulators 63 of 195 Final Update 3 Report Drug Effectiveness Review Project head-to-head randomized controlled trials or observational studies comparing one targeted immune modulator to another and evidence was insufficient to make indirect comparisons. We included one recent, good-quality systematic review and meta-analysis of all four targeted immune modulators approved by the US Food and Drug Administration for Crohn’s 190 disease. The review assessed two outcomes, failure of remission and relapse of disease activity, and analyzed the subgroup of patients with fistulizing disease separately. Overall, the 191-196 review included 27 randomized controlled trials: eight on adalimumab, seven on 197-201 202-208 209-213 certolizumab pegol, seven on infliximab, and six on natalizumab. Pooled results regarding the general efficacy of targeted immune modulators for Crohn’s disease showed consistent results. Infliximab demonstrated statistically significant greater efficacy than placebo for inducing remission and preventing relapse in all patients and in healing 190 and maintaining remission in fistulizing Crohn’s disease. Natalizumab was superior to placebo 190 in inducing remission and preventing relapse in patients with Crohn’s disease. Adalimumab demonstrated statistically significant greater efficacy than placebo for inducing remission. Both single trials on evaluating the efficacy of adalimumab for maintaining response demonstrated statistically significant greater efficacy than placebo. Certolizumab pegol was superior to placebo only in preventing relapse but there was a trend showing a greater efficacy than placebo in 190 inducing remission. Overall, Adalimumab and certolizumab pegol were not shown to be more efficacious compared with placebo for inducing remission and healing in fistulizing Crohn’s 190 disease. In particular, the evidence from currently available trials on investigating the efficacy of targeted immune modulators in patients with fistulizing Crohn’s disease was insufficient. We did not find any evidence that met our eligibility criteria on the general efficacy of abatacept, alefacept, anakinra, etanercept, golimumab, rituximab, tocilizumab, or ustekinumab for the treatment of Crohn’s disease. Although some studies allowed stable doses of other immunomodulatory agents, no conclusive evidence exists to determine whether combination treatment of targeted immune modulators with other agents (azathioprine, 6-mercaptopurine or methotrexate) leads to clinically and statistically greater improvements than monotherapy. We did not include studies of targeted immune modulators compared with active therapies for Crohn’s disease. We found no studies that met our eligibility criteria assessing the comparative or general efficacy of any targeted immune modulator in pediatric populations. Study populations and outcome measures Most of the included efficacy studies were conducted in narrowly defined populations and/or were limited to less than 1 year of follow-up. Generally, patients were allowed to remain on stable doses of corticosteroids in all trials. Some trials involved tapering of corticosteroids in the evaluation of maintenance. All patients suffered from active Crohn’s disease for at least 3 months. Some patients also had abdominal or perianal fistulas, a serious complication of Crohn’s disease characterized by abnormal connection between the gut and the skin with small bowel or colonic contents draining to the skin surface for at least 3 months. Most studies included patients with a Crohn’s Disease Activity Index score between 220 and 400. However, some trials included patients with Crohn’s Disease Activity Index scores as high as 450 (i. Disease duration and concomitant treatments varied across studies. On average, disease duration ranged from 8 to 12 years. Many studies allowed concomitant treatment with 5- aminosalicylate, antibiotics, corticosteroids, azathioprine, 6-mercaptopurine, or methotrexate. Targeted immune modulators 64 of 195 Final Update 3 Report Drug Effectiveness Review Project Most studies utilized the Crohn’s Disease Activity Index to characterize disease severity. The Crohn’s Disease Activity Index assesses eight related variables (e. Response commonly was characterized by a Crohn’s Disease Activity Index reduction greater than or equal to 70 points. Several studies utilized the Inflammatory Bowel Disease Questionnaire. This questionnaire identifies 32 individual items categorized within four major quality of life domains (primary bowel symptoms, systemic symptoms, social impairment, and altered emotional function). Some studies assessed surrogate parameters such as C-reactive protein concentrations as an objective marker for inflammation. In studies specifically designed to assess fistulizing disease, outcomes included 50% reduction in the number of draining fistulas or a complete absence in draining fistulas. It is based on the assessment of five dimensions: subjective reporting of disease severity, presence of extraintestinal manifestations, physical 214 examination findings, weight and height, and blood tests. Sponsorship All of the randomized controlled trials received funding from the pharmaceutical industry. The included meta-analysis was funded by the American College of Gastroenterology. Several studies also received funding from the National Institutes of Health or the US Food and Drug Administration. Detailed assessment: Direct evidence on the comparative effectiveness We did not identify any head-to-head studies for the treatment of Crohn’s disease. Detailed assessment: Indirect evidence on the comparative effectiveness We did not identify any indirect comparisons of targeted immune modulators for the treatment of Crohn’s disease. Included placebo-controlled trials were too heterogeneous to conduct adjusted indirect comparisons. Detailed assessment: Evidence on the general efficacy Because of the lack of head-to-head trials, we reviewed placebo-controlled trials. Table 13 summarizes studies included for general efficacy. Adalimumab We included one systematic review and meta-analysis for adalimumab compared with 190 placebo. The review presented pooled results for two outcomes (failure to achieve remission and failure to prevent relapse) in all patients and in the subgroup of patients with fistulizing disease. Overall, up to eight trials provided evidence from up to 1462 patients. In addition, we presented results on further outcomes such as quality of life when this information was available from the original publications. Targeted immune modulators 65 of 195 Final Update 3 Report Drug Effectiveness Review Project To assess the efficacy of adalimumab for preventing the failure to achieve remission in 190 active Crohn’s disease one review included three randomized placebo-controlled trials with a 191-193 total of 714 patients.
HIV-associated Skin and Mucocutaneous Diseases 615 Appendix: Frequent especially HIV-associated skin diseases Acute HIV exanthema: after HIV transmission buy generic vermox 100mg on line hiv symptoms immediately after infection, 40-90% of patients develop an acute best order vermox hiv symptoms three months after infection, febrile buy vermox 100mg fast delivery jiangmin antivirus guard, mononucleosis-like disease with constitutional symptoms and exanthema (see chapter on Acute HIV-1 Infection). This nonspecific eruption starts 1 to 3 weeks after transmission, and weeks before HIV seroconversion. The macular exanthema favors the upper trunk and is characterized as fairly non-pruritic with erythematous macules from 0. Morbilliform or rubella-like eruptions and palmoplantar hyperkeratotic eczema occur less frequently. Histopathology reveals a non-specific perivascular and interstitial infiltrate in the upper- and mid-dermis (Barnadas 1997). Oral aphthous ulcers frequently in combination with shallow genital ulcers (bipolar aphthosis) are another important clinical symptom (Hulse- bosch 1990, Porras-Luque 1998). Differential diagnosis includes viral infections (EBV, CMV), Mediterranean spotted fever (Segura 2002), secondary syphilis, drug erup- tions (Hecht 2002, Daar 2001) and Behcet’s disease. Anal cancer: See chapters on STDs (Condylomata acuminata) and Cervical and Anal Cancer. Aphthous ulcers: At least three different kinds of aphthous ulcers can occur in the oral cavity of HIV+ patients. The most frequent diagnosis is recurrent aphthous stom- atitis (canker sores) (1) with single or few painful lesions usually localized in the vestibule of the mouth. The ulcers occur at sites of mechanical injuries, are 3 to 10 mm in diameter and heal spontaneously after a few days. Single or multiple large aphthae (2) which are >1 cm in diameter and usually persist for several weeks are less common. In a few cases, especially when multiple small lesions occur, herpes simplex viruses can be involved. Large ulcers in combination with severe immunodeficiency can be caused by cytomegalovirus, usually part of a generalized CMV infection. Bipolar aphthosis (3) involving the oral and genital mucosal membranes is an important clinical symptom of acute HIV infection or Behcet’s disease. In addition to these clinical variants of aphthous ulcers several authors have discussed the direct role of HIV in aphthous stomatitis (Kerr 2003). The treatment of recurrent aphthosis is based on topical anes- thetics and corticosteroids. Large persistent aphthae can require intralesional corti- costeroids or systemic prednisone. Immunomodulators such as thalidomide are sug- gested for use as prophylaxis in patients with frequent and painful recurrences. Folliculitis: pustular, papular or edematous-papular follicular lesions, involving the proximal limbs and the upper trunk. Possible causes include Staphylococcus, Malassezia furfur, Demodex folliculorum and drugs like indinavir. Treatment depends on the etiologic agent detected by bacterial swabs and histopathology if needed. Antimicrobials against staphylococcus and malassezia or changing the antiretrovi- ral regimen may be required. DADPS, a 10% crotamiton or polidocanol ointment or low-dose UVB 311 nm radiation are effective against severe pruritus in these patients (Holmes 2001, Simpson-Dent 1999). Today, it is well-established that ART-naïve patients with pruritic eosinophilic folliculitis significantly improve with ART. Genital warts (condylomata acuminata): See chapters on STDs (Condylomata acumi- nata) and Cervical and Anal Cancer. Herpes simplex virus / Herpes zoster infections: see chapter on AIDS. Immune reconstitution inflammatory syndrome (IRIS)-related skin reactions: ART supports the TH-1 immune response and the tuberculin test reactivity recovers (Girardi 2002). In association with this immune reconstitution clinical manifesta- 616 Interdisciplinary Medicine tions of herpes zoster, mucocutaneous herpes simplex infections, mycobacterial infections, eosinophilic folliculitis, foreign body granulomas and cutaneous sar- coidosis have been reported (Handa 2001, Hirsch 2004, Beatty 2010). These infec- tious, as well as some non-infectious inflammatory skin diseases occur within a few days to 3 months after the initiation of ART. The therapy depends on the severity of clinical manifestations and consists of specific antibiotics, steroidal and non- steroidal anti-inflammatory drugs (see chapter on IRIS). Kaposi sarcoma: the most frequent malignant tumor of the skin and mucosal mem- branes associated with HIV infection (see chapter on Kaposi’s sarcoma). Lipodystrophy: See chapter on Lipodystrophy syndrome. Malignant cutaneous lymphomas: Malignant B and T cell lymphomas are rare in HIV-infected patients (Beylot-Barry 1999, Biggar 2001). Cutaneous B cell lymphomas usually grow as red to violaceous nodules and are easily mistaken for Kaposi’s sarcoma. They can also look like persistent hematoma or non-specific asymptomatic papules. A biopsy should be performed on any clinically unclear tumor of the skin. Cutaneous T cell lymphomas are rare malignancies in HIV+ patients. The prevalence among 2,149 HIV-infected patients in Frankfurt was 0. The clinical course starts with non-specific eczematous patches (Stage I), which are usually not diagnosed as cutaneous lymphoma even after several biopsies because of the paucity of findings such as cellular atypia. These lesions are usually diagnosed as eczematous dermati- tis. A linear pattern of patchy or slightly infiltrated lesions in the relaxed skin tension lines can be an early clinical indication of cutaneous T cell lymphoma known as parapsoriasis (Munoz-Peres 1999). Histopathology becomes more evident during the plaque stage (Stage II), and is striking when in Stage III multiple tumors of the mycosis fungoides present. Biggar (2001) calculated a relative risk for cutaneous T cell lym- phomas in HIV+ patients of 15. The leukemic phase (Sézary syndrome) is characterized by erythroderma involving the palms and soles. In patients with erythroderma who have darker skin types and lack the histopathological signs of cutaneous T cell lymphoma the so-called pseudo-Sézary syndrome has to be considered in the differential diagnosis (Picard-Dahan 1996). Solitary tumors can be controlled by radiotherapy (20–24 Gy) or photodynamic therapy (Paech 2002). Widespread, multiple tumors and Sézary syn- drome are treated with a combination of retinoids and interferons or chemother- apy. Recently, remission of a CD8-positive pseudolymphoma treated solely with ART was reported (Schartz 2003).
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