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. However, for historical reasons, KS is 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 human herpes virus 8 (HHV-8), the virus that causes KS, two will develop KS within 10 years. KS has always been rare among HIV-positive drug users and people with haemophilia (Atkinson 2004). A small number of gay men in the United States have KS but do not have HIV infection or AIDS. KS is rare among women, possibly due to hormonal factors, but is still more common in HIV-positive than HIV-negative women (Atkinson 2004; Hessol 2004). 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, but it is rarely a cause of death. Nevertheless, KS is associated with an elevated risk of death and there is some evidence that it can accelerate 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, unlike bruises. 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 the introduction of highly active antiretroviral therapy (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 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.

KS lesions sometimes occur in addition to a condition called multicentric Castleman'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.

Human herpes virus 8

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).

HHV-8's 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's lymphoma. 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 97% of them. Other types of human tissue rarely contain HHV-8, although it has been isolated from some AIDS-related B-cell lymphomas.

The reason why 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 cell 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 possibly 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 alfa (IntronA / Roferon-A / Viraferon) and interferon beta (Avonex / Rebif / Betaferon), are being tested as treatments for KS.

A number of antibody tests for HHV-8 have been developed for research purposes, although these continue to lack sensitivity. A new generation of HHV-8 assays has been developed which may improve understanding of HHV-8 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 also 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 between 1982 and 1999 found that receptive anal intercourse, insertive rimming, and insertive fisting were significant risk factors for HHV-8 seropositivity (O'Brien 1999). Other studies have supported the link between anal sex and rimming and HHV-8 transmission (Diamond 2001; Grulich 1997). 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 2002).

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 1999). Another study found 30% of tissue samples taken from the mouths and throats of 30 HHV-8 / HIV co-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 2000; Casper 2004). 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.

These findings suggest that HHV-8 in saliva may play an important role in HHV-8 transmission. 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 2000; Vaithilingum 2000). Social factors such as poor nutrition, poverty, poor hygiene and crowded living conditions may also contribute to the transmission of HHV-8 in Africa (Moore 1995), while HIV infection is known to increase the risk of childhood acquisition of HHV-8 (Phiri 2004).

Possible co-factors

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 over-activated, with elevated cytokine levels stimulating the growth of early KS cells, which can eventually 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 to cause additional lesions.

One of the overactive substances that may cause the development of KS lesions is oncostatin M, a growth factor that is secreted by activated T-cells that stimulates angiogenesis. Infections such as HIV that activate T-cells may lead to an increase in levels of oncostatin M. KS cells also produce high levels of other angiogenic factors such as basic fibroblast growth factor and interleukin-1 β.

The presence of HIV itself may play a role in KS. 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 studies have shown that HIV-infected T-cells secrete a substance called vascular endothelial growth factor (VEGF) 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. Similarly, early theories that KS might be caused by cytomegalovirus (CMV) have now been discounted.

There have also been suggestions that KS might be linked to the recreational drug amyl nitrate (poppers), since KS is an AIDS-defining symptom largely restricted to gay and bisexual men, the most frequent users of poppers. A number of studies found that gay and bisexual men who have used poppers are much more likely to have developed KS as an AIDS-defining illness than non-users, but other studies have shown no clear relationship. One current hypothesis is that poppers could stimulate angiogenesis by turning up the expression of VEGF and its receptors, as has been demonstrated in the mouse (Tran 2003).

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 microglial cells in the brain.

Diagnosis

The best way to diagnose KS is by biopsy - taking a 4 to 6mm 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 polymerase chain reaction (PCR) viral load tests for HHV-8 have been developed but are not widely available. However, 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 has found that people with KS lesions had higher levels of HHV-8 and that high or rising levels were associated with the progression of KS. HHV-8 levels fall when KS is 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.

Kaposi's sarcoma in the age of highly active antiretroviral therapy

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 2000). Although protease inhibitor- and non-nucleoside reverse transcriptase inhibitor-based HAART regimens have similar efficacy in causing KS regression (Martinez 2004), there is some evidence that HIV protease inhibitors may have direct 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 6700 HIV-positive gay men in the United States, no new cases of KS were seen in 1996. This was a dramatic reduction from 1993 to 1995 that coincided with the widespread introduction of protease inhibitors. In another large study of over 5000 gay and bisexual men in the United States, incidence of KS peaked in 1985 at 26 cases per 1000 person-years, dropping to 7.5 cases per 1000 person-years in 1996 to 1997. The EuroSIDA study has reported a similar fall in incidence in its study of over 7000 individuals from Europe, Israel and Argentina, decreasing further to an incidence of 2 cases per 1000 person-years in 2002 (Mocroft 2004).

Although KS is rarer in women than in men, a similar drop in incidence has been observed in women since the introduction of HAART (Hessol 2004).

A small Italian study found that HAART caused a complete resolution of KS in seven of nine people, while 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 cell count of 174 cells/mm³ showed that the magnitude of the CD4 cell count increase after commencing HAART predicted the likelihood that KS would disappear. 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 2000). However, these results have not been replicated in other studies, which have failed to show an effect of CD4 cell count on KS remission, although sustained suppression of HIV viral load did show an association with regression (Martinez 2004).

Patients taking HAART are likely to develop KS if they fail to have good virological or immunological response to antiretroviral treatment. Furthermore, despite the dramatically reduced incidence of the disease, gay men taking HAART are still more likely to develop KS than individuals from other risk groups (Mocroft 2004).

Studies have shown that it may take more than a year for an effective HAART regimen to lead to loss of HHV-8 in HIV-positive patients, whether they have symptomatic KS or not (Bourboulia 2004). HAART regimens have also been shown to reduce the shedding of HHV-8 in saliva, with regimens containing drugs from the three major classes being the most effective (Casper 2004).

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

The development of MCD is associated with increased risk of KS disease progression, particularly if lymphoma develops (Oksenhendler 2003; Martinez 2003; Thirlwell 203). A cluster of rapidly progressing MCD has been reported among people taking antiretroviral therapy in the United States. Three people with a history of KS and HHV-8 infection developed symptoms of MCD after initiation of HAART, and two died within a week of diagnosis (Zietz 1999). However, many people with MCD can be managed in the long-term with the use of chemotherapy (Neuville 2003; Oksenhendler 2003).

Rapid progression, development and spread of cancerous lesions or tumours have been reported in patients responding to HAART. It is postulated that these growths are an immune reconstitution response to HHV-8, leading to worsening or new appearance of KS or MCD (Hosseinipour 2004).

Treatment

After a diagnosis of KS is made, several factors are weighed in deciding whether to treat it, including:

• The number of lesions.

• CD4 cell count.

• The presence of associated symptoms such as fever, night sweats or weight loss.

• Prior opportunistic infections.

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. Deciding to leave KS untreated also avoids the toxic effects of chemotherapy, which may also be immunosuppressive.

There are a range of treatments available for KS. These include local or general chemotherapy and pathogenesis-based treatments. The current standard of care for KS is liposomal doxorubicin (Caelyx / Myocet). 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 World Health Organization 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. Radiotherapy kills 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, 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 (Velbe) or vincristine (Oncovin), 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 areas of thin skin such as the face and the genitals, and is most successful if the KS lesion is flat, not nodular and relatively small.

Interferon alfa

Interferon alfa 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, with CD4 cell counts above 200 cells/mm³ 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 to 50% of people taking it, although this may take two to three weeks to do so.

People who respond to interferon alfa 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 (zidovudine, Retrovir) plus α-interferon. Most trials found that this resulted in tumour regression in more than 40% of cases. KS in people with low CD4 cell counts is more likely to respond to AZT plus interferon alfa than to interferon alfa alone.

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

Cytotoxic chemotherapy

Cytotoxic chemotherapy is a form of treatment given by injection into a vein. These treatments poison fast-growing cells, like KS cells, more than normal cells. However, they can also affect other cells in the body that normally grow quickly, in the bone marrow, hair follicles and the gut, causing anaemia, immune damage, hair loss and diarrhoea. Different chemotherapy drugs 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 (Etopophos / Vepecid), tenoposide, vinblastine and vincristine. They are somewhat effective, but after a period of time their effect may diminish and the KS may progress. Vinorelbine (Navelbine) is a newer chemotherapy drug now being tested in trials.

Paclitaxel (Taxol) has been licensed in the United States for the second-line treatment of KS. In the United Kingdom 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 Pneumocystis pneumonia (PCP) prophylaxis while receiving chemotherapy, because the treatment causes immunosuppression and 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 (DaunoXome), are now licensed in the United Kingdom and are considered to be the standard of care for KS.

Liposomes are microscopic bubbles of fat that enclose drug molecules. 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 is licensed for the treatment of KS among people with CD4 cell counts below 200 cells/mm³ 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 20mg/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 (Northfelt 1998). Furthermore, a Spanish study has shown that adding liposomal doxorubicin to a HAART regimen increases the rate of partial or complete remission of moderate or severe KS (Martin-Carbonero 2004).

The major side-effect is bone marrow suppression, which occurs in around 50% of people, leading to leukopenia, anaemia 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 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 granulocyte colony stimulating factor (G-CSF), which promotes the growth of white blood cells.

Liposomal daunorubicin, is used to treat KS, with similar response rates to liposomal doxorubicin. It is approved in the United Kingdom for initial treatment of advanced KS, as an alternative to combination chemotherapy regimens.

A comparative analysis of clinical trial data of the two products found liposomal doxorubicin to be more effective than daunorubicin, with response rates of 59 and 25%. 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 this treatment.

A number of studies have shown that 9-cis-retinoic acid gel (Panretin) is effective in treating KS lesions. An American study found a 39% response rate to retinoic acid gel in an intention-to-treat analysis (Thommes 1998).

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

The gel was given licensing approval in the United States as a topical treatment for Kaposi's sarcoma in November 1998.

Retinoic capsules have been developed for oral administration, but they cause significant toxicity.

Treatments for human herpes virus 8

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.

Drugs used to treat other herpes virus infections, such as ganciclovir (Cymevene), foscarnet (Foscavir), cidofovir (Vistide) and aciclovir (Zovirax) have been tested against HHV-8. In test tube studies, aciclovir has no effects against HHV-8, ganciclovir and foscarnet have only modest effects, and cidofovir has strong effects. Trials of cidofovir as a treatment for KS are now taking place in the United States.

Other evidence that these drugs may be effective against KS has come from studies of people who received foscarnet or ganciclovir as treatment for cytomegalovirus (CMV) retinitis, although findings were mixed. 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 the drug. Receiving ganciclovir did not seem to affect the risk of developing KS. In a French study of over 16,000 people, neither foscarnet nor ganciclovir was linked to a reduced risk of KS. Lastly, in a study of over 3500 people in the United Kingdom, 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 intravenous anti-CMV drugs have been discounted as treatments for KS due to severe toxicity.

Better-tolerated broad-spectrum anti-viral drugs such as adefovir (Hepsera) and lobucavir have been developed but there is no information yet about effects against HHV-8.

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 KS 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.

However, 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, while other groups have found that the injections had no obvious benefits but caused substantial side-effects, including irritability and anxiety serious enough to require psychiatric treatment.

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, 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 (Dovonex) as a treatment for KS on the skin. A different ointment containing the antiviral agent n-docosanol (Lidakol) is also being studied in trials in the United States.

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.

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).