Abacavir hypersensitivity

Abacavir causes a hypersensitivity reaction (HSR), which may be life-threatening if not recognized in time. It occurs in approximately 5-8 of patients (Chirouze 2005, Clay 2002, reviews in Hewitt 2002). A higher rate is noted in patients on a once-daily regime (James 2005). The HSR occurs after a median of 8 days, and within the first 6 weeks in 93 of cases. Studies have found a correlation between the HLA type (particularly HLA-B 57) and the occurrence of HSR (Hetherington 2002, Mallal 2002,...

STI for Immunological Reasons

Hardly any patient has become as famous as the acutely infected homosexual man treated in a Berlin private practice a few years ago who, with a viral load of approximately 80,000 copies ml, began a HAART regimen consisting of didanosine, indinavir and hydroxyurea. The virus rapidly became undetectable. After several problems - and two short treatment interruptions - HAART was finally stopped after 176 days. Surprisingly, even without drugs, plasma viremia has remained below the level of...

Indinavir

Paronychia of the toes or fingers and ingrown toenails are typical side effects of indinavir, occurring in 4 to 9 of patients. Furthermore, approximately 30 of patients receiving indinavir show two or more mucocutaneous changes, such as cutaneous xerosis, cheilitis, hair loss or alopecia, resembling retinoid-like side effects. Indinavir is the only antiretroviral drug that induces retinoid-like effects, as it probably interferes with the retinoid metabolism. There is no relation to sex, age or...

Signs symptoms and diagnosis

In contrast to the classical KS found in older men, in whom the tumors usually occur on the lower legs and feet, HIV-associated KS does not have a preferential pattern of localization. It can begin on any area of the skin, but may also appear on oral, genital, or ocular mucous membranes. Typical findings are initially solitary, or a few asymptomatic purple macules or nodules, which have a predilection for distribution along relaxed skin tension lines. Disease progression is variable the macules...

The morphologic structure of HIV1

HIV-1 viral particles have a diameter of 100 nm and are surrounded by a lipoprotein membrane. Each viral particle contains 72 glycoprotein complexes, which are integrated into this lipid membrane, and are each composed of trimers of an external glycoprotein gp120 and a transmembrane spanning protein gp41. The bonding between gp120 and gp41 is only loose and therefore gp120 may be shed spontaneously within the local environment. Glycoprotein gp120 may also be detected in the serum (6) as well as...

Lopinavirr

Metabolism LPV is co-formulated with Ritonavir and primarily metabolised by CYP3A4. LPV r is a strong inhibitor of CYP3A4 and induces the glucuronidation pathway as well as CYP 2C9 and CYP 2C19 1 . TDF T 32 (Cmax 15 f), LPV r Adequate plasma concentration In the expanded access program of Viread and ABT-418 no increase in side-effects observed. EFV 600 QD + LPV r BID 3 LPV 25 (Cmin 44 ) 1. LPV r 400 100 + NVP 200 BID Extensively pre-treated patients 4 LPV r 27 (Cmin 51 ) 2. LPV r 400 100 +...

Nevirapine

Nevirapine is a frequently prescribed NNRTI, which is also used successfully for the prevention of mother-to-child transmission. As with all NNRTIs, a single point mutation is sufficient to develop high-level resistance. Nevirapine is very useful for simplification of successful HAART regimens. In order to prevent allergic reactions, lead-in dosing is always required. Nevirapine has good long-term tolerability with a favorable lipid profile. The main problem, besides development of resistance,...

Dendritic cells as prototypes of antigenpresenting cells

Dendritic cells, macrophages and B cells represent the main antigen-presenting cells of the immune system. Dendritic cells (DC) are the most potent inducers of specific immune responses and are considered essential for the initiation of primary antigen-specific immune reactions. DC precursors migrate from the bone marrow towards the primary lymphatic organs and into the submucosal tissue of the gut, the genitourinary system and the respiratory tracts. They are able to pick up and process...

Pancreatitis

Up to 7 of patients treated with didanosine suffer from pancreatitis. Occasionally, stavudine, lamivudine and zalcitabine cause pancreatitis too. The combinations of didanosine plus stavudine or didanosine plus tenofovir carry a particularly high risk for pancreatitis. Alcohol consumption and treatment with pentamidine are further risk factors. The mechanism by which didanosine triggers pancreatitis is not known but may be influenced by its metabolism through the purine pathway (Moyle 2004). A...

Peripheral polyneuropathy

Peripheral polyneuropathy is mainly caused by the NRTIs, zalcitabine, didanosine and stavudine. It usually presents with a distal symmetrical distribution and sensorimotor paralysis. Patients complain of paresthesia and pain in their hands and feet, and often, with zalcitabine, about perioral dysesthesia. The symptoms often begin gradually after several months of therapy. HIV infection itself can lead to peripheral polyneuropathy, but the drug-induced form becomes apparent much earlier and may...

Introduction

Since 1981, when the first reports about AIDS were published in medical literature, skin and mucocutaneous diseases played an important role in the clinical diagnosis of acquired immunodeficiency. Kaposi's sarcoma in young homosexual men was the first symptom that made AIDS a visible disease (Friedman-Kien 1981, 1990). Additionally, opportunistic infections of the skin and oral cavity such as herpes simplex and candidiasis were published as being clinical markers of acquired immunodeficiency...

Antiretroviral transmission prophylaxis Combination prophylaxis

Standard combination antiretroviral regimens for the treatment of HIV infection should be discussed and offered to all pregnant women with HIV regardless of the viral load. They are clearly recommended if the viral load is > 10,000 copies ml. Combination prophylaxis should be introduced temporarily from 32+0 weeks gestation until immediately after birth (Table 4). The combination of AZT+3TC is problematic because of the possible development of resistance in the M184 codon (Mandelbrot 2001)....

Pneumocystis Pneumonia PCP

PCP is still one of the most frequent OIs. This interstitial pneumonia, from which most patients died in the early years of the HIV epidemic, is caused by pneumo-cysts. In the last 20 years, there has been significant progress in the knowledge about this organism, especially through DNA analysis detailed review in Thomas 2004 . Although Pneumocystis was previously classified as a protozoan, it was established in 1988 that it is in fact an unusual type of fungus Edman 1988 . In the 1990s, it was...

Treatment

No specific treatment has been established to date. Diarrhea is self-limiting with a good immune status therefore, poor immune status should always be improved with HAART - and this often leads to resolution Carr 1998, Miao 2000 . To ensure absorption of antiretroviral drugs, generous symptomatic treatment with loperamide and or opium tincture is advised. If this is unsuccessful, treatment with other anti-diarrheal medications, perhaps even sandostatin, can be attempted. Sufficient hydration is...

HIV and HBV coinfection Introduction

The hepatitis B virus is one of the most common human pathogens worldwide. Up to 95 of all HIV-infected patients have been infected with hepatitis B, and approximately 10-15 have chronic hepatitis B, with considerable variation among geographical regions and risk groups. It is estimated that around 100,000 HIV-infected patients in the USA suffer from chronic hepatitis B. Sexual transmission is the most frequent route of contraction. Transmission via the bloodstream is more probable than for HIV...

References

Antinori A, Cingolani A, Alba L, et al. Better response to chemotherapy and prolonged survival in AIDS-related lymphomas responding to HAART. AIDS 2001, 15 1483-91. 2. Besson C, Goubar A, Gabarre J, et al. Changes in AIDS-related lymphoma since the era of HAART. Blood 2001, 98 2339-44. 3. Boulanger E, Agbalika F, Maarek O, et al. A clinical, molecular and cytogenetic study of 12 cases of human herpes virus 8 associated primary effusion lymphoma in HIV-infected patients. Hematol J 2001, 2...

Individual agents Special features and problems

Abacavir Ziagen is a guanosine analog with good CNS penetration. Earlier studies have shown that this drug can lower viral load by approximately 1.4 logs within 4 weeks, but that resistance develops relatively rapidly Harrigan 2000 . Abacavir is phosphorylated intracellularly to carbovir triphosphate, which has a long half-life Harris 2002 . In October 2004, abacavir was licensed for once-daily therapy Gazzard 2003, Clumeck 2004 . Abacavir is also a component of Trizivir , together with AZT...

Which boosted combination is best

There is relatively little clinical data available yet from direct comparisons between boosted PI regimens. So far, no major differences have become apparent in the randomized MaxCmin1 Trial, the efficacy of saquinavir r and indinavir r was comparable. The drop-out rate in the indinavir r group was significantly higher, probably due to side effects Dragstedt 2003 . In the MaxCmin2 Study, both treatment-naive and treatment-experienced patients were randomized to receive either saqui-navir r soft...

Entry inhibitors

There are three crucial steps for entry of HIV into the CD4 T cell 1. binding of HIV via the gp120 envelope protein to the CD4 receptor attachment - target of attachment inhibitors , 2. binding to coreceptors target of coreceptor antagonists via conformational changes to gp120, and finally 3. fusion of virus and cell target of fusion inhibitors . Drugs which interfere with these steps are currently summarized as entry inhibitors. Even if the antiviral effects of most drugs now being tested are...

Immunotherapy and its relevance in clinical practice

In recent years, in addition to conventional ART, immunomodulatory treatment strategies have been investigated to an increasing extent reviews in Mitsuyasu 2002, Sereti et Lane 2001 . All of these therapies still lack proof of clinical benefit. Some important approaches are nevertheless addressed briefly below. Interleukin-2 IL-2, aldesleukin, Proleukin is a cytokine that is produced by activated T cells and which induces proliferation and cytokine production in T cells, B cells and NK cells...

New protease inhibitors PIs

Progress with new PIs is modest overall, despite the fact that there is a big fanfare anytime one of the involved companies has any in vitro data suggesting activity against PI-resistant viruses. Many substances have been lost along the way. Besides tipranavir and perhaps TMC 114, there is not much to look forward to in the midterm. Tipranavir Aptivus is the first non-peptidic protease inhibitor. It was initially a product from Pharmacia Upjohn, and has now been developed for some time by...

Treatment and prophylaxis of mitochondrial toxicity

Drug interactions may precipitate mitochondrial symptoms and must be taken into account. The mitochondrial toxicity of didanosine VidexTM for example is augmented through drug interactions with ribavirin, hydroxyurea and allopurinol Ray 2004 . When didanosine is combined with tenofovir VireadTM , the didanosine dose must be reduced to 250 mg QD. An impairment of mitochondrial metabolism may also result from comedication with ibuprofen, valproic acid and acetyl salicylic acid - these substances...

Contributors

Partners AIDS Research Center Massachusetts General Hospital Bldg. 149, 13th Street, 5th floor Charlestown, MA 02129 USA Phone 1 617 724 2461 Fax 1 617 724 8586 MAltfeld partners.org Max Brauer Allee 45 D - 22765 Hamburg Phone 49 40 3903534 Fax 49 40 3903948 Dr.Aries web.de Klinische Immunologie Zentrum Innere Medizin der Medizinischen Hochschule Carl-Neuberg-Stra e 1 D - 30625 Hannover Phone 49 511 532 5393 Fax 49 511 532 9067 Grindelpraxis Hamburg Grindelallee 35 D - 20146 Hamburg Phone 49 40...

Combination products

In August 2004, the US FDA licensed two new combination drugs Truvada and Kivexa . These drugs will certainly create new options for antiretroviral therapy both products will significantly reduce the pill burden of many regimens, as each is given daily as a single tablet. In 2004, Gilead, BMS and Merck together announced a new combination pill of FTC, tenofovir and efavirenz. However, it will take another one to two years for this to happen. Experience from Africa and Thailand has shown that...

New nucleoside analogs

Since the development of the guanosine analog DAPD came to a halt, hopes are now focused mainly on cytidine analogs. The most promising substances are currently elvucitabine, reverset and SPD-754. Mitochondrial toxicity seems to be low, and most are effective against hepatitis B. One problem with cytidine analogs could be the combination with the cytidine analog 3TC, where a loss of efficacy seems possible. ACH-126,433 Elvucitabine is a nucleoside analog developed by Achillion Pharmaceuticals....

The organization of the viral genome

Most replication competent retroviruses depend on three genes gag, pol and env gag means group-antigen, pol represents polymerase and env is for envelope overview in 9 Fig. 2 . The classical structural scheme of a retroviral genome is 5'LTR-gag-pol-env-LTR 3'. The LTR long terminal repeat regions represent the two end parts of the viral genome, that are connected to the cellular DNA of the host cell after integration and do not encode for any viral proteins. The gag and env genes code for the...