Kaposi's sarcoma (KS) was first described in 1872 by the Hungarian dermatologist Moritz Kaposi. Before the AIDS epidemic it was a rare condition.

There are four different forms of KS:
**Classic KS causes multiple skin lesions on the lower limbs. It is mainly seen in elderly men in Mediterranean or Eastern European regions.
**Endemic KS is found in children and young men in equatorial Africa. It is more virulent than the classic form.
**Acquired KS occurs in people treated with immunosuppressive drugs, especially those who have received organ transplants. It goes away when the drugs are stopped.
**Epidemic KS is the form associated with HIV infection. It tends to follow a more variable but potentially more aggressive course than other forms of KS.

KS most commonly presents as skin lesions which often appear when the immune system is still relatively intact. As long as it is confined to the skin, KS is not fatal and it is unlikely to be serious. But for historical reasons, KS is in itself diagnostic of AIDS. While it is most commonly found on the skin, KS can occur anywhere in the body.

Within the context of HIV/AIDS, KS predominantly affects gay men with HIV. For every five men infected with both HIV and HHV-8 (the virus which causes KS), two will develop KS within 10 years. KS has always been rare among HIV-positive drug users and people with haemophilia. A small number of gay men in the USA have KS but do not have HIV infection or AIDS. KS is rare among women, possibly due to hormonal factors. If a woman with HIV develops KS, she is likely to have contracted HIV through unsafe sex with a bisexual man. KS may be more aggressive when it does occur in women.

KS used to be the most commonly diagnosed HIV-related malignancy. With the development of better treatments for KS, and the use of antiretroviral therapy, the incidence of KS declined significantly in the 1990s in western countries. KS remains a common opportunistic malignancy in people who have relatively advanced immunosuppression. As a cause of death, it is relatively uncommon. Nevertheless, KS is associated with a greater risk of death and there is some evidence that KS accelerates HIV disease.

Symptoms

When KS lesions first appear on the skin, they are often flat patches with a pink or blood-bruise colour. They develop into nodules: hard, raised, round or oval lumps which do not go white when they are pressed (as bruises do). Their colour is violet, bluish or reddish in light-skinned people. A bruise-like discoloration and minor swelling often appear at the edges of lesions when they are enlarging. When many nodules are present, they often appear in roughly symmetrical patterns on each side of the body and may follow the skin fold lines of the body. In some cases, the nodules can ulcerate, bleed and become infected with secondary infections.

Especially on the thighs and soles of the feet, KS lesions can form large plaques which are often swollen and painful. KS in the mouth is common, often on the roof or the gums, and may occasionally cause difficulties with chewing or swallowing.

While KS mostly commonly occurs on the skin, it can develop anywhere in the body including the lymph nodes, lungs or intestines. Prior to HAART, 40% of people with KS skin lesions also had lesions in their intestines. Conversely, KS can develop internally in the absence of skin lesions. In the intestines, KS is usually harmless but can sometimes cause a blockage, resulting in nausea, vomiting, abdominal pain and occasionally bleeding.

In the lymph nodes, blocked fluid drainage may cause swelling, especially in the feet, lower legs or genitals. Occasionally swelling occurs around the eyes.

KS lesions sometimes occur in addition to a condition called Multicentric Castlemen's Disease (MCD). This is a disorder of resulting from over-activity of lymph tissue. MDC is characterised by swollen lymph nodes, fever, fatigue, weight loss, night sweats, blood disorders and sometimes liver and spleen irregularities. It is thought to be caused by HHV-8 and is associated with a high prevalence of tumours and poor prognosis. MCD may develop into a type of HHV8-associated lymphoma.

KS in the lungs (pulmonary KS) is the most serious form, and can be fatal. It can lead to recurrent chest infections or accumulation of fluid on the lung (pleural effusion). There may be blood in spit, cough and breathlessness.

HHV-8 - the cause of KS

There is now consensus in scientific circles that KS is caused by a herpes virus. The virus was first named Kaposi's sarcoma-associated herpesvirus (KSHV) but is now usually known as human herpesvirus 8 (HHV-8).

Its genetic material was discovered in KS lesions in late 1994. In March 1996, researchers in San Francisco successfully grew the virus in culture. The virus is a close relative of Epstein-Barr virus, which has been proposed as the cause of non-Hodgkin lymphoma (see Non-Hodgkin lymphoma in the A to Z of illnesses).

Recent studies have confirmed that HHV-8 can almost always be found in KS lesions - including non-HIV-related KS - but is very rare in other body tissues. Nine studies in which samples from 224 KS lesions were examined found that HHV-8's genetic material could be identified in 211 of them, or 97%. Other types of human tissue rarely contain HHV-8, although it has been isolated from some AIDS-related B-cell lymphomas.

The reason that some people infected with both HIV and HHV-8 develop KS, while others do not, appears to be linked to HHV-8 rather than CD4 count. A study found that the presence of HHV-8 genetic material in both blood cells and saliva was associated with KS, while people with HHV-8 only in saliva were much less likely to have KS lesions (Cannon 2003).

Scientists have uncovered a number of different ways in which HHV-8's genes, alone or combined with HIV (and perhaps other undiscovered factors), may trigger abnormal blood vessel growth. Kaposi's sarcoma is caused by a complex process of HHV-8 infection, the production of inflammatory cytokines and the dysregulation of new blood vessel formation (angiogenesis). Drugs which suppress vessel formation, such as interferon alpha and beta, are now being tested as KS treatments.

A number of antibody tests for HHV-8 have been developed for research purposes, although these tests continue to lack sensitivity. A new generation of HHV-8 assays has been developed which may improve understanding of HHV8 and lead to clinical use of HHV-8 testing.

Transmission of HHV-8

HHV-8 is spread sexually, through mother-to-child contact, and via organ transplant. A growing body of research suggests that the relatively high levels of HHV-8 in saliva may contribute to HHV-8 transmission.

HHV-8 was originally thought to be transmitted through anal sex and rimming (oral-anal sex) because of its high prevalence among gay men. Certainly there is considerable evidence to suggest that HHV-8 is spread through sexual contact between men, although the actual mechanism remains elusive. A study of 259 HIV-positive men followed since 1982 found that receptive anal intercourse, insertive rimming, and insertive fisting were significant risk factors for HHV-8 seropositivity (O'Brien). Other studies have supported the link between anal sex and rimming and HHV-8 transmission (Diamond;Grulich). Most recently, new HHV-8 infection among gay men has been associated with an HIV-positive partner, rather than any specific sexual practice, and use of amyl nitrate (Casper).

However, very little HHV-8 has been found in the sexual fluid of people infected with the virus. For example, HHV-8 was detected in only one sample from six HHV-8/HIV-positive men and in the cervico-vaginal secretions of only one of 13 women infected with both HHV-8 and HIV-1(Calabro). Another study found 30% of tissue samples taken from the mouths and throats of the 30 HHV-8/HIV-infected men contained HHV-8 compared with 1% of anal and genital samples. In addition, HHV-8 viral load in the mouth and throat was much higher than viral in other tissues (Pauk). Similar results have been reported among women. HHV-8 DNA was found in a third of salivary samples taken from 34 HHV-8-infected women but in no cervical samples (Lucchini).

These findings suggest that HHV-8 in saliva may play an important role in HHV-8 transmission (Pauk). This theory accords with the high prevalence of HHV-8 in Africa, where HHV-8 is thought to be acquired during infancy or early childhood. It has been suggested that HHV-8 is transmitted to children through maternal saliva when women pre-chew their infants' food (Hladik; Vaithilingum). Social factors such as poor nutrition, poverty, poor hygiene and crowded living conditions may contribute to the transmission of HHV-8 in Africa (Moore).

Possible co-factors for KS

There are other theories about factors that could cause or act as co-factors to the development of KS. One hypothesis suggests that KS develops because the immune system is overactivated. Some research has found that KS cells can originally develop as a result of abnormalities in levels of cytokines, chemical messengers in the body. These early KS cells do not appear to be genuinely cancerous at all. Once established, KS cells themselves secrete cytokines that promote their own growth and which stimulate other cells also to release cytokines that promote KS cell growth. Eventually, in some cases but not all, the cells become cancerous. Once these cells have arisen in one part of the body they may spread in the bloodstream until they lodge in other tissues and cause lesions there too.

One of the overactive substances that may cause the development of KS lesions is called oncostatin M. This is a growth factor that is secreted by activated T-lymphocytes; thus, infections such as HIV or STDs that activate lymphocytes may lead to an increase in levels of oncostatin M. Oncostatin M is only one of a number of angiogenic growth factors - factors that stimulate the development of blood vessels. KS cells also seem to produce high levels of other angiogenic factors such as basic fibroblast growth factor and interleukin-1 beta (IL-1 beta).

The presence of HIV itself may play a role. Studies have shown that the HIV tat gene seems to cause the development of KS-like lesions in mice, and the tat protein produced by this gene stimulates the growth of human KS cells in the test-tube. Antibodies against tat appeared to block the development of KS cells in the test-tube. Other research has shown that HIV-infected T cells secrete a substance called VEGF-A which may induce vascular leakage and facilitate the development of KS.

The human papilloma virus (HPV), associated with cervical and anal cancer, is no longer considered to be a co-factor in the development of KS. Early theories that KS might be caused by cytomegalovirus (CMV) have now been almost universally discounted.

Retrospective studies have found that people with KS have a significantly reduced chance of developing HIV-related dementia. Researchers are investigating the mechanism by which HHV-8 inhibits HIV infection of the microglia.

Diagnosis

The best way to diagnose KS is by biopsy - taking a 4-6 mm sample of a skin lesion and examining it under the microscope. However, some doctors experienced in treating HIV may be able to diagnose KS without performing a biopsy.

Lesions in the lung can be inspected using a flexible fibre-optic instrument called a bronchoscope, but biopsy samples are generally not taken because of the risk of causing internal bleeding or a collapsed lung. Chest X-rays and scans can also reveal the presence of lung tumours. KS in the intestines can be viewed with a fibre-optic endoscope, but biopsy samples often test negative because the lesions themselves are under the surface, rather than on it.

Antibody and PCR viral load tests for HHV-8 have been developed but are not widely available. The LANA test looks for a particular HHV-8 antigen, whereas the PCR test measures HHV-8 virus in the blood. Not everyone who has been infected with HHV-8 has detectable HHV-8 in the blood. Currently, the two tests are considered equally effective at determining a person's risk of developing KS.

Preliminary research found that people with KS lesions had higher levels of HHV-8. High or rising levels were seen in people whose KS was progressing. HHV-8 levels fell when KS was treated with chemotherapy. In the future, it is possible that blood levels of spindle cells, growth factors and certain hormones may be measured to help in the diagnosis of KS.

No one should attempt to self-diagnose KS: lots of things can look and feel like KS (e.g. bruises, bites, and infections).

KS in the age of HAART

In the age of HAART, KS generally responds well to therapy (Thirlwell 2003). KS often significantly improves and blood levels of HHV-8 drop dramatically when HAART is commenced. This clinical improvement is thought to be due to the drugs' restoration of immune function, rather than any direct anti-KS effects (Leao). However, there is some evidence that HIV protease inhibitors may also have anti-HHV-8 effects. If the drugs start to fail and HIV viral load increases, KS is likely to progress again.

The widespread use of anti-HIV therapy has produced a reduction in the number of KS cases. In a study of 6,700 HIV-positive gay men in the USA, no new cases of KS were seen in 1996 - a dramatic reduction from 1993-1995 that coincides with the widespread use of protease inhibitors. Another large study of over 5000 gay and bisexual men in the US, incidence of KS peaked in 1985 at 26 cases per 1000 person-years, and dropped to 7.5 cases per 1000 person years in 1996-97.

A small Italian study found highly active antiretroviral therapy (HAART) resolved KS completely in seven of nine people with KS. A larger British study found that HAART was an effective and durable treatment for KS (Bower 1999). A study of 53 people diagnosed with KS at a mean CD4 count of 174 showed that the magnitude of CD4 count increase after commencing HAART predicted the likelihood that KS would disappear once HAART began. In total, 72% of those who started HAART after a KS diagnosis had a complete or partial remission of their KS within 48 weeks (Renato).

In the era of HAART, the prognosis of people with KS is poorest when they have both advanced tumours and advanced systemic disease (Nasti 2003).

The development of Castleman's disease is associated with increased risk of disease progression, particularly if lymphoma develops (Oksenhendler; Martinez; Thirlwell). A cluster of rapidly progressing multicentric Castleman's disease has been reported among people taking antiretroviral therapy in the US. Three people with histories of KS and HHV-8 infection developed symptoms of Castleman's disease after initiation of HAART, and two died within a week of diagnosis (Zietz 1999). However, many people with Castleman's disease can be managed in the long-term with the use of chemotherapy (Oksenhendler; Neuville 2003).

Treatment

After a diagnosis of KS is made, several factors are weighed in deciding whether to treat it, including whether there is a large number of lesions; whether the CD4 count is low; whether there are associated symptoms such as fever, night sweats or weight loss; and whether the individual has had prior opportunistic infections. The presence of these factors is associated with a poorer prognosis, indicating that treatment may be advisable.

KS may be an early sign of immune deficiency. If a person is not on anti-HIV treatment, KS lesions may signal the need for treatment, although viral load, CD4 count and other factors should be considered when making this decision.

Many doctors and people with HIV are unwilling to treat KS that is restricted to a few skin lesions and causing no problems. If these are disfiguring, advice on cosmetic camouflage make-up is available from many clinics and self-help groups. KS on the skin is not, in itself, a life-threatening condition and there is no evidence that the treatment of one or two small skin lesions makes any difference to life-expectancy. This uncertainty has to be weighed against the toxic effects of chemotherapy, which may also be immunosuppressive. The technical words for tumour improvement are regression or remission, both of which can be partial or complete.

If you do decide to treat skin lesions, or your KS is severe enough that treatment is necessary (such as painful lesions on the soles of the feet), there is a range of options. Treatment can be broadly divided into two camps: chemotherapy (local or general) and pathogenesis-based treatments. The current standard of care for KS is liposomal doxorubicin. Specific treatment for KS may be used in addition to antiretroviral therapy.

Chemotherapy for KS may be difficult in countries where access to drugs outside the WHO Essential Drugs List is limited, because the only chemotherapy agents included in this list are vincristine and methotrexate, both of which have shown limited efficacy in treating KS lesions.

Local therapy

Localised radiation therapy (radiotherapy) can be used to treat KS lesions in the mouth or throat, painful skin lesions or lesions that are causing blockages in the lymph nodes of the face, arms and legs. It is also effective for lesions on the eyelids or the white of the eye. The idea is to kill the over-active tumour cells with a series of low doses of radiation, leaving the rest of the body untouched. Side-effects can include short-term reddening of the skin and hair loss and, in the mouth, inflammation of the mucous membranes (mucositis), which can sometimes be severe or even life-threatening. The lesions usually leave a scar, like a mole, where pigmentation remains in the skin. This is particularly common when long-standing lesions are treated.

Alternatively, individual skin lesions can be injected with chemotherapy drugs such as diluted vinblastine or vincristine, which causes the lesion to swell up painfully but then shrink or disappear, leaving a scar. Other approaches to treating skin lesions including removing them surgically or freezing them with liquid nitrogen (cryotherapy). Cryotherapy is usually reserved for thin areas of skin such as the face and the genitals, and is most successful if the KS lesion is flat, not nodular, and relatively small.

Alpha interferon

Alpha interferon has been reported to be a helpful treatment for some people with KS. The best results have been seen when it is used by people with early KS, limited to the skin, and whose immune systems are not severely damaged, for example those with CD4 counts above 200 and no history of opportunistic infections or symptoms such as fever, weight loss or night sweats. In this group, it has been shown to improve KS in about 30-50 % of people taking it, although this may take two to three weeks. (People who do respond to interferon may be recommended to continue taking a maintenance dose for as long as they can tolerate it. Researchers have also examined the combination of AZT plus alpha interferon. Most trials found that this resulted in tumour regression in more than 40% of cases. KS in people with low CD4 counts is more likely to respond to AZT plus alpha interferon than to alpha interferon alone.

Interferon has to be injected into the skin, which is fairly easy for most people to learn to do themselves, and usually causes side-effects of flu-like symptoms. It can also cause neutropenia - shortage of white blood cells called neutrophils which fight infections. This can leave the individual vulnerable to bacterial infections. The neutropenia may be avoidable by using the growth factor GM-CSF to stimulate neutrophil and white blood cell production.

Cytotoxic chemotherapy

Cytotoxic chemotherapy is a form of treatment given by injection into a vein. Chemotherapy just means `drug treatment'. Cytotoxic means `poisonous to cells'. The idea of these treatments is that they poison fast-growing cells, like KS cells, more than normal cells. But there are also other cells which normally grow quickly. These include cells in the bone marrow, hair follicles and the gut. So side-effects of these drugs tend to include bone marrow damage (resulting in anaemia and some immune damage), hair loss (alopecia) and diarrhoea. Different drugs all cause slightly different side-effects, so a cytotoxic chemotherapy regimen is tailor-made for each person. For example, if someone already had bone marrow damage from AZT, it would be better to use a drug like vincristine, which causes less marrow damage.

Before the advent of liposomal chemotherapy, treatment usually consisted of a combination of three or more different drugs. Cytotoxic drugs include bleomycin, doxorubicin, etoposide (VP-16), tenoposide, vinblastine and vincristine. They are somewhat effective, but after a period of time their effect may diminish and the KS may progress. Vinorelbine is a newer chemotherapy drug now being tested in trials.

Paclitaxel, often known by its tradename Taxol has been licensed in the USA for the second-line treatment of KS. In the UK it is approved for treating certain forms of ovarian cancer. It has been shown to have a 59% response rate and studies directly comparing paclitaxel and doxorubicin are ongoing.

It is important to take PCP prophylaxis while receiving chemotherapy, because the treatment itself causes immunosuppression which increases the risk of opportunistic infections.

Liposomal chemotherapy

Researchers have developed new, less toxic formulations of chemotherapy drugs. Two such drugs, liposomal doxorubicin and liposomal daunorubicin, are now licensed in the UK and are considered to be the standard of care for KS.

Liposomes are a method of enclosing a drug in microscopic bubbles of fat. These have several theoretical advantages. The liposomes circulate in the bloodstream without releasing the drug. The drug is only released when the liposome leaves the bloodstream and lodges in the body tissues. This is most likely to happen within KS lesions, because the lesions are made up of a mass of abnormally growing blood vessels that are very 'leaky'. Thus, the chemotherapy is targeted to the lesions, wherever they are in the body, with less of the drug affecting non-cancerous areas and thus fewer side-effects.

In Europe liposomal doxorubicin (known by the tradename Caelyx) is licensed for the treatment of Kaposi's sarcoma among people with CD4 counts below 200 and extensive skin or visceral lesions, either as first-line or salvage therapy. It has been shown to be more effective than the combination of bleomycin and vincristine as initial treatment for KS, and less toxic. The recommended dose is 20 mg/m² every two to three weeks. About 90% of treated people tend to have a stabilisation or some reduction in the number or size of their KS lesions. This is difficult to compare with other trials as different methods are often used to measure the tumour burden (number, size and location of tumours).

One trial that compared standard chemotherapy and pegylated liposomal doxorubicin found the latter was the superior treatment. The response rate was 46% in the doxorubicin group and 25% in the chemotherapy group (Northfelt 1998).

The major side-effect is bone marrow suppression is about 50% of treated people, leading to leucopenia, anaemia and/or thrombocytopenia. Other side-effects may include inflammation of the mouth (stomatitis) and hair loss. These are side-effects seen with the parent drug doxorubicin; however, doxorubicin's most serious side-effect of damage to the heart muscle is far less likely with the liposomal form. Some recipients have developed an unusual side-effect of ulcers on the hands and feet, known as hand-foot syndrome. Neutropenia caused by liposomal doxorubicin or other drugs can be treated with an agent such as G-CSF which promotes the growth of white cells.

Another chemotherapy drug, daunorubicin, is used in liposomal form for treating KS, with similar response rates to liposomal doxorubicin. It is approved in the UK for initial treatment of advanced KS, as an alternative to combination chemotherapy regimens. In a study at the Kobler Centre which enrolled people with early KS, one group was treated immediately with liposomal daunorubicin and the other group received no treatment. The treated people had some improvement in their KS.

A comparative analysis of clinical trial data of the two products found liposomal doxorubicin to be more effective than daunorubicin (59% versus 25% response rates). There have been anecdotal reports that people who have stopped responding to one liposomal drug may benefit from switching to the other.

Retinoic acid

Topical and oral retinoic acid has been tested for treatment of KS, and there is evidence that about one-third of people with KS lesions respond to treatment.

A number of studies have shown that 9-cis-retinoic acid gel (ALRT-1057) known by the brand name Panretin to be effective in treating KS lesions. An American study found a 39% response rate to retinoic acid gel in an intention-to-treat analysis (Thommes).

Two 12 week randomised, placebo-controlled studies of retinoic acid gel have been conducted. In the Australian study, the gel was applied twice day. The response rate to the gel was 37%, while 44% remained stable and 19% progressed; in comparison, 7% on placebo had a response, 58% remained stable and 35% progressed. In the American study, retinoic acid gel was applied three times a day, escalating to four times a day in the absence of side-effects, and found similar results. In both studies, resolution of KS occurred across a range of CD4 counts and was independent of anti-retroviral therapy, although there was a correlation between higher CD4 counts and protease inhibitor therapy, and positive response to retinoic acid gel.

U.S. approval of Panretin made by Ligand Pharmaceuticals as a topical treatment for Kaposi's sarcoma was granted in November 1998.

Panretin capsules known as alitretinoin are also being developed by Ligand. A similar product has been called LGD1069 (under the tradename Targretin). Significant toxicity has been reported with the oral treatment.

Anti-HHV-8 treatments

Based on the evidence that KS may be caused by a virus that belongs to the herpes family, drugs that inhibit that virus could help to treat KS.

Recently, researchers have started to look for drugs that inhibit HHV-8, and to test whether these are effective at reducing the number or size of KS lesions. There is also interest in whether these drugs can prevent KS from appearing in the first place.

HHV-8 belongs to the herpes virus family, so anti-viral drugs such as ganciclovir, foscarnet and cidofovir (used to treat CMV) and acyclovir (used to treat herpes simplex) have been tested against HHV-8. In test-tube studies, acyclovir has no effects against HHV-8, ganciclovir and foscarnet have only modest effects, and cidofovir has quite strong effects. Trials of cidofovir as a treatment for KS are now taking place in the USA.

Other evidence that the anti-CMV drugs may be effective against KS has come from studies of people who received foscarnet or ganciclovir as treatment for CMV retinitis - although not all of these studies agree. In a study of over 20,000 HIV-positive Americans, people who received foscarnet at any time were 70% less likely to develop KS than people who never received foscarnet. Receiving ganciclovir did not seem to affect the risk of developing KS. In a French study of over 16,000 people, neither foscarnet or ganciclovir was linked to a reduced risk of KS. Lastly, in a study of over 3,500 people in the UK, people who received foscarnet or ganciclovir seemed less likely to develop KS.

A pilot study in which people with KS were treated with intravenous foscarnet found that lesions did decrease during treatment. However, retrospective studies involving foscarnet have found conflicting results in terms of its ability to halt or slow the development of KS. Despite some encouraging results, the IV anti-CMV drugs have been discounted as treatments for KS due to severe toxicity.

Several better-tolerated broad-spectrum anti-viral drugs are in development, such as adefovir or lobucavir, but there is no information yet about effects against HHV-8. Test-tube studies suggest that HHV-8 is highly sensitive to cidofovir.

Experimental treatments

Several experimental treatments for KS are also currently being studied.

SU5416 is a new drug believed to have some effect on the growth of AIDS-related Kaposi's sarcoma tumours by slowing the production of new blood vessels.

Early studies in mice found that when female mice became pregnant, the KS lesions became smaller or disappeared altogether. Researchers found that a female hormone produced at high levels during pregnancy seemed to be killing the KS cells. A human form of this hormone, called human chorionic gonadotrophin (HCG) is already a licensed treatment for certain infertility problems.

The action of this hormone may explain the rarity of KS in women, as well as two case reports in which women with KS whose lesions spontaneously disappeared when they became pregnant. Experiments using HCG as a treatment for people with KS have produced mixed results. One group of researchers said that injections of HCG caused lesions to shrink with few side-effects; other groups, including doctors in London, found that the injections had no obvious benefits but caused substantial side-effects, including irritability and anxiety serious enough to require psychiatric treatment. It is also very expensive.

In photodynamic therapy (PDT), the individual is injected with a drug that concentrates in KS lesions and other fast-replicating cells. The KS lesions are then exposed to a laser light, which converts the drug to a form of oxygen that kills the cells. A trial of PDT is under way in London. Side-effects include a generalised hypersensitivity to light, such that even a cloudy day can lead to a bad sunburn, which may last several weeks or months.

Research is under way into an ointment called calcipotriol as a treatment for KS on the skin. A different ointment containing the antiviral agent n-docosanol, known by the trade-name Lidakol cream, is also being studied in trials in the USA.

In test-tube studies anti-angiogenic drugs, which interfere in the process by which new blood vessels grow within cancerous tumours, suppress the growth of KS in animal cells, but the two drugs studied to date, SP-PG and TNP-470, have been discontinued after they failed to show efficacy. Trials of other anti-angiogenic drugs, such as interleukin-12 and thalidomide, are continuing.

Another experimental avenue involves the use of tat inhibitors. If tat does play an important role in the pathogenesis of KS, drugs that target it may have specific benefits for people with KS in addition to anti-HIV effects. However, a pilot trial with Ro 24-7429, a tat inhibitor developed by Roche, found no evidence of anti-KS effects at the maximum tolerated dose. Ro 24-7429 is no longer being developed after studies found that it had no anti-HIV effects either.

Interleukin-12 has also been tried as a treatment for KS in combination with liposomal doxorubicin. Results from a small observational study have been encouraging, with a response rate of 83% in 26 patients with advanced KS (Little 2003).