In addition to being at increased risk for certain life-threatening infections, people with HIV/AIDS can get cancer of the brain. One form of brain cancer is called PCNSL--primary central nervous system lymphoma. The standard treatment is to beam radiation at the entire brain. This reduces the size of the tumour(s), but does not appear to have a major impact on survival.
To understand the relationship between injection drug use, malnutrition and HIV infection, researchers studied 36 women, some of whom were infected with HIV and all of whom injected drugs. In general, the doctors found that the type of immunity needed to control the infections seen in AIDS was severely weakened in both HIV-infected and non-HIV-infected women.
Vitamins and minerals have different functions in the body. B-complex vitamins, for example, help release energy from food and iron helps red blood cells transport oxygen. Other minerals, particularly copper, manganese, selenium and zinc are used by the body to make antioxidant enzymes. These enzymes help protect cells from harmful chemicals produced by "oxidative stress."
In people with HIV infection, weakened immunity--perhaps caused by dysfunctional CD8+ cells--allows herpes infection to get out of control. The virus that causes these lesions is called HSV (herpes simplex virus). Skin lesions caused by the virus can be painful and may grow worse if left untreated. Standard treatment is acyclovir tablets or cream.
Some types of HPV (human papilloma virus) can cause warts on the skin, others on the genitals and still others have been associated with cervical cancer. There is no cure for HPV infection but depending on the location of the wart, several treatments have been used--podofilox (Condylox), interferon-alpha and liquid nitrogen. Now researchers at the 3M company have developed a drug called Aldara (imiquimod) that helps the immune system destroy the wart.
Triple therapy with protease inhibitors is associated with increased survival compared to other regimens. Protease inhibitors greatly decrease the amount of HIV in the blood, causing levels of CD4+ cells to rise. Much has been made about the viral load in the blood, but since most HIV is located in the lymph nodes, it is only reasonable that research should focus there.
Cytokines are chemicals used by cells of the immune system to send signals to each other. Different cytokines, such as interleukin-2 and interferon-alpha, send different messages. High levels of some cytokines appear to promote high levels of HIV production. That is why some researchers want to test drugs that reduce cytokine levels and in turn suppress HIV.
The American Food and Drug Administration (FDA) has approved a new version of saquinavir called Fortovase. The drug will be available in American pharmacies in late November 1997 and should cost the same as the older version of saquinavir. Fortovase comes in soft-gel capsules. Much more of the drug is absorbed, which leads to greater anti-HIV activity.
Although drugs can be absorbed and reach the blood, they may not necessarily enter certain parts of the body such as the brain, eyes and testicles. Some researchers fear that those parts of the body could harbour HIV and act as a breeding ground even though virus levels have fallen in other areas due to drug therapy.
In an attempt to increase the anti-HIV activity of treatment regimens, doctors are now testing combinations of two protease inhibitors. These drugs interact with one another, usually increasing the amount of at least one of them that gets into the blood, as well as perhaps increasing the time the drugs remain in the blood. Much of the information on double protease combinations comes from small studies.
Researchers have reported that absorption of anti-TB drugs may be reduced in PHAs. Doctors in Canada recently published their work on this, confirming the problem. Malabsorption of drugs seems to occur even in PHAs who are symptom-free and is worse in PHAs with symptoms of HIV infection. The Canadian research is important because it may draw attention to a similar issue in another area--protease inhibitors.
Daunorubicin is a drug used to treat leukemia. Recently it has been reformulated--the drug has been packed into tiny balls of "fatty material" called liposomes. In its new liposomal form, daunorubicin is called DaunoXome. Recently, the drug appeared to have activity in PHAs with less than 20 KS lesions.
One of the hallmarks of AIDS is the life-threatening brain infection 'crypto' (cryptococcal meningitis). Signs and symptoms include headache, fever, nausea/vomiting and an "altered mental state." Standard treatment is 4-6 weeks of intravenous amphotericin B (AmB) followed by life-long maintenance therapy with fluconazole or itraconazole.
We are hearing more and more reports of bacteria that are able to resist the effects of antibiotics. In order to find new compounds with antibacterial activity, researchers are turning to essential oils from selected plants. These plants and/or their extracts have been used for centuries to treat wounds and infections and may yield new treatments.
Essential oils have been known to have healing and infection-fighting properties for centuries. Only recently have the oils been analysed to understand these effects. Naturopaths have available about 300 essential oils with which they can treat their patients, although the average person would probably use only up to 10 of them.
Chemokines are molecules that cells of the immune system use to send signals to each other. Generally, by releasing chemokines cells can form a chemical trail allowing other cells to follow and gather at sites of infection. Cells have receptors for chemokines which allow them to capture this molecule so that they can receive its message.
As more people use protease inhibitors, the range of side effects associated with these drugs increases. In addition to changes in triglyceride, cholesterol and blood sugar levels, the use of protease inhibitors has recently been associated with changes in body shape. Increased fat around the abdomen, commonly called 'Crix belly', and reduced muscles on the arms and legs are often noted by people who take protease inhibitors.
In November of this year, IAPAC (International Association of Physicians in AIDS Care) will release details of its plan to test a live HIV vaccine in humans. The trial is expected to begin in the year 2000. Developed in the USA, the vaccine to be used is a form of HIV-1 that has been severely weakened by the removal of 5 pieces of genetic information.
Given the huge number of deaths due to HIV infection and the lack of a cure, many are calling for an increased focus on vaccine research. IAPAC (International Association of Physicians in AIDS Care) has recently begun a campaign to test a weakened HIV vaccine in people. IAPAC points to research on a similar vaccine using SIV, which causes AIDS in monkeys, that seemed to protect some monkeys from developing AIDS.
In the late 1980s reports appeared of cases of syphilis in HIV-infected people that did not respond to standard treatment. Indeed, in some cases, the microbe that causes syphilis, T. pallidum, had been found in the fluid surrounding the brain even after treatment with penicillin. Some doctors think that T. pallidum has become resistant to standard anti-syphilis therapy. Others think that like many illnesses seen in AIDS, HIV infection has made syphilis more difficult to treat.
Doctors recruited over 1,000 PHAs for this study to compare the effects of triple therapy -- indinavir with AZT (or d4T) and 3TC -- against double therapy with a combination of two nukes -- AZT (or d4T) and 3TC. PHAs receiving triple therapy had their risk of developing AIDS or dying fall by 50% compared to PHAs receiving double therapy. This study confirms the benefit doctors have seen in some of their patients who use protease inhibitors.
When AZT was first approved by the FDA (Food and Drug Administration), it was supposed to be taken every 4 hours. In a recent clinical trial called ACTG 320 (see next article), it was given 3 times daily. Now researchers in the US have completed a one-year study comparing the effects of AZT twice daily versus every 4 hours. They found no difference between the two groups when looking at the number of PHAs developing AIDS or dying.
The anti-cancer drug Hydrea (hydroxyurea) has anti-HIV activity when used by itself in lab experiments. When used together with the antiviral ddI, it boosts levels of ddI inside cells, thereby increasing its anti-HIV effect. As a result, this combination is being tested in people at various stages of HIV infection. Most recently, in a study of 21 people pre-treated with or intolerant to AZT, a combination of ddI/Hydrea was able to reduce the level of HIV in the blood to 1/10th its pre-study value, but only for 12 to 16 weeks.
The anti-HIV drug indinavir (Crixivan) is the most widely used protease inhibitor in North America. According to the manufacturer, Merck Frosst, 4% of people who used the drug in clinical trials developed kidney stones (nephrolithiasis). Now a study of 240 people at the NIH (National Institutes of Health, Bethesda, Maryland) has confirmed the 4% figure but also found that 11% of all subjects developed symptoms of some degree of kidney damage.
Monitoring levels of CD4+ cells helps doctors keep track of the state of the immune system. As CD4+ cell counts are used when making decisions about therapies it is important that the counts are as accurate as possible. Several factors can affect CD4+ cell counts including the time of day the blood was drawn, stress and exercise. Researchers in England have focused on people at rest and found that in that state, CD4+ cell counts can fall by 38% and CD8+ counts by 32% compared to blood taken from people who had not been resting.
The antibiotic clarithromycin (Biaxin«) is useful in treating MAC (mycobacterium avium complex) infection as well as the life-threatening brain infection toxo (toxoplasmosis). Researchers in the USA studied the effect of using clarithromycin with AZT. They found that taking the antibiotic with AZT reduced levels of AZT in the blood. To get around this problem they suggest that AZT and clarithromycin be taken at least 2 hours apart.
Experiments on animals and people have shown that excessive alcohol use can damage the liver, pancreas and weaken the immune system. Whether or not drinking alcohol increases production of HIV in people with this infection or if it increases the "risk of non-HIV-infected people becoming infected" (by weakening the immune system versus impairing their judgment) has not been determined.
A virus related to small pox called MC (Molluscum contagiosum) can infect the skin, and particularly the face, of PHAs. Infection causes small raised lesions that look like bumps. The virus produces chemicals that hamper the immune system's ability to destroy it. Although MC doesn't normally kill PHAs , the bumps are annoying and can spread. In severe cases the lesions may grow larger.
Unrelated to any other AIDS drug on the market, GS 840 (adefovir dipivoxil) is being tested in several studies for different reasons: as a treatment for HIV/AIDS, CMV infection and hepatitis B. One HIV/AIDS study will hopefully be taking place in Canada later this year, as will the hepatitis B study. Given at a dose of 120 mg/day, GS 840 has resulted in a small decrease in the amount of HIV in the blood.
Researchers in the US have found a type of bacteria that contains a protein with powerful antiviral activity. The protein called CV-N (cyanovirin N) permanently damages HIV-1 (and related viruses HIV-2 and SIV) thus preventing the virus from infecting cells. CV-N has potential therefore as an anti-HIV drug. What some people find exciting about this is that the type of algae used were cyanobacteria or blue-green algae.
In lab experiments low concentrations of the organic extract, but not the freeze-dried extract, protected about 90% of cells from death due to HIV. The plant extract did not appear to cause any toxicity. Calendula's anti-HIV activity occurs because the plant affects a vital viral enzyme called RT (reverse transcriptase) which is also the target of AZT and the "related" drugs, 3TC, d4T, ddC, ddI and 1592.
Thalidomide is known to cause birth defects and nerve damage. In non-HIV-infected people the drug appears to be "well tolerated." In the early 1990s, when more PHAs began to use thalidomide, doctors noticed that it was not as "well tolerated" as it had been when the drug was first used in the early 1960s.
One problem arising from HIV infection is that the insulation covering nerve fibres can become damaged. The information being sent along these nerves then leaks and does not arrive intact. In some people this is linked with problems with memory. Treating the 'insulation' damage may correct the HIV-associated memory problems. Use of the amino acid methionine seems to help improve memory of some PHAs in one small study.
Baclofen (Atrofen, Lioresal) is used to help block the transmission of certain nerve impulses reducing the intensity and number of spasms, pain and muscle stiffness. In non-HIV-infected people, the drug has been useful in the treatment of persistent hiccups. One team of doctors in New Jersey has stated that persistent hiccups "is a relatively common complaint" among their HIV-infected patients.
Baclofen (Atrofen, Lioresal) is used to help block the transmission of certain nerve impulses reducing the intensity and number of spasms, pain and muscle stiffness. In non-HIV-infected people, the drug has been useful in the treatment of persistent hiccups. One team of doctors in New Jersey has stated that persistent hiccups "is a relatively common complaint" among their HIV-infected patients.
Extracted from the leaves of a small Australian tree, the first documented use of tea tree oil was in the 1930s. Australian dentists used it to kill bacteria in the mouths of their patients. Doctors also began to report the oil's positive effect in treating wounds and ulcers. In the 1960s, American doctors reported its usefulness in treating boils and vaginal infections.
Infection with certain intestinal parasites can cause life-threatening diarrhea and weight loss in people with AIDS. Although treatment with the drugs albendazole and Flagyl« can help the immune system get rid of several parasites, these drugs do not help eliminate another parasite -- E. bieneusi.
People with AIDS can develop painful ulcers in the mouth/throat as a result of herpes or syphilis. In some cases, however, cells of the immune system attacking those locations can cause ulcers to form (called apthous ulcers). Treatment can include corticosteroids (eg. prednisone) either placed on the ulcer or taken as tablets. Not all people respond to this therapy and the ulcers often recur.
Since its anti-HIV activity was discovered in 1987, the drug carbovir has undergone much testing. Unfortunately, absorption of carbovir was poor, it caused kidney and heart damage at relatively low doses and poorly penetrated the brain/spinal cord. So researchers at Glaxo-Wellcome turned and twisted the carbovir molecule and came out with the drug 1592, also called abacavir.
A series of anti-HIV drugs called antisense compounds (for an explanation of antisense and how it works see the latter part of this article) is under development in North America. Hybridon Inc. has recently halted a trial of one of its antisense products, GEM 91 (gene expression modulation). In reviewing its data the company found that 10 days of iv exposure to the drug caused reduced levels of platelets -- which are needed to help blood clot -- in 3 of 9 volunteers.
The American Food and Drug Administration (FDA) has warned doctors in the US about the possibility of protease inhibitors causing a new side effect -- diabetes. (Further information on diabetes appears several paragraphs below) This side effect has been noted in people taking all 4 protease inhibitors (PI) approved for use in the US
Tylenol is a popular pain reliever because it works for many people. However, for people with damaged livers or kidneys, Tylenol may not be safe. Since people with HIV/AIDS may already have livers burdened by the use of various medications, attacks by viruses that cause liver damage and alcohol use, adding Tylenol may increase liver damage.
Unintentional weight loss can be a problem for some people with HIV/AIDS. It may be caused by a variety of factors, including a reduced ability to absorb nutrients, infections of the intestines or changes in energy cycles. PHAs tend to lose muscle (lean body mass) because the body breaks down muscle to form the protein it needs. Women with HIV infection lose both fat and muscle.
In North American popular culture it is commonly accepted that stress can affect the immune system and may be involved in the development of cancer and AIDS. In one study, researchers found that stress increased the chance of breast cancer recurring. In another, doctors found that women with breast cancer who were in a support group and who also received chemotherapy lived longer than other women with breast cancer who received the same chemotherapy but did not get psychosocial support.
Just as women with HIV infection can be at greater risk of cervical cancer, some men with HIV infection are also at increased risk of anal cancer. Doctors in San Francisco recently reviewed their records on 97 patients diagnosed and treated for anal cancer over a period of 8 years. The reviewers found 8 male PHAs in this group of 97.
On June 23, an advisory panel of the American Food and Drug Administration voted 8-0 for approving Taxol™ (paclitaxel) as a treatment for Kaposi's sarcoma (KS), a cancer that can occur in some people with HIV/AIDS. The panel recommended that Taxol not be used as the therapy of choice for treating KS, but rather as a second option. Currently there is no effective therapy for KS, although interferon-alpha together with AZT,
An infection caused by the fungus Candida, is called candidiasis. Such infections can cause discomfort and, indirectly, can lead to weight loss in PHAs. The fungus usually tends to attack the mouth, throat and vagina, though it can move from the throat further into the digestive tract. Although different regimens of the drug fluconazole can prevent these infections, everyday use of this drug for all PHAs is usually not recommended because of its high cost, the potential for drug interactions and the risk of developing fungal infections which may be resistant to fluconazole.
To protect cells from harmful chemical reactions, the body makes antioxidant enzymes using the molecule GSH (glutathione). Researchers in Italy have been studying the effect of hepatitis C virus (HCV) infection on the liver and the body's production of GSH. According to their results, people with chronic HCV have less than normal levels of GSH and may therefore benefit from supplements designed to boost GSH levels.
Although initial infection with hepatitis C virus (HCV) does not immediately destroy the liver, the virus slowly spreads through that organ as infected liver cells produce more HCV. This state of continual production of HCV is called chronic infection and occurs in about 50% of HCV-infected people. Symptoms of HCV are mild, fatigue being the most common.
Most studies of HIV-related weight loss have focussed on males. This research has provided useful ways to manage weight loss and low energy levels in HIV-infected men. Now doctors are finally studying similar problems in HIV-infected women, the results of some of which we report below.
In general, treatment with protease inhibitors has driven the amount of HIV in the blood so low that it can barely be detected. This has given the immune system some relief and space for a limited recovery, allowing PHAs to withstand some infections and perhaps live longer than they otherwise might.
IL-2 (interleukin-2) is a chemical produced by the immune system which causes T cells to grow and helps them fight infections. Since production of IL-2 decreases as the immune system weakens, it is being tested in several studies to see if it can help rebuild the immune systems of PHAs. IL-2 is available in North America as a treatment for kidney cancer.
The new anti-HIV drug DMP 266, which is related to nevirapine and delavirdine, is being studied in combination with other drugs at several hospitals in the US. We now report results from the first 10 months of one of those studies
T cells contain genetic material (called DNA) that carries instructions for making proteins that the cells need to carry out their functions. When HIV infects a T cell, the virus inserts its genetic material (or genes) into that of the cell. HIV's genes can then hijack the cell and convert it into a virus factory. Researchers at several companies in the USA have now developed small molecules called antisense compounds, "usually short pieces of DNA", that work inside HIV-infected cells by homing in on the virus's genes and stopping them from working.
PWAs can develop bone marrow damage because of infection by HIV and other microbes, cancer and the toxicity of certain drugs. This damage can reduce the production of certain white blood cells called neutrophils. When the level of neutrophils falls below normal (a condition known as neutropenia), people become at risk for developing serious bacterial and fungal infections.
People with HIV/AIDS can develop peripheral neuropathy (PN) -- damage to the nerves in the hands, arms, feet and legs. Several anti-HIV drugs can cause PN, including ddC, ddI and d4T. PN may also be caused by direct damage to nerves from CMV and HIV. Symptoms of PN include sharp "shooting" pains, tingling, and loss of sense of touch.
Researchers in California have monitored over 200 volunteers with HIV infection measuring their levels of glutathione (GSH) and survival. Over a period of 2-3 years the researchers found that people with less than normal levels of GSH were less likely to survive than people with normal levels of GSH. Moreover, supplements of NAC (N-acetyl-cysteine), which is used to make GSH, prolong survival
As a result of chemical reactions, highly active molecules called free radicals are formed. Produced under carefully controlled conditions, free radicals can be useful. Indeed, some cells of the immune system make free radicals which they use when destroying microbes. But when the production of free radicals is uncontrolled they can cause damage.
Doxorubicin is an anticancer drug that's been repackaged into tiny bubbles of fat called liposomes. The bubbles are coated with PEG (polyethylene glycol) which helps them resist being processed by the body. The drug thus remains in circulation longer than non-PEG-coated liposomes. The reason for using liposomes is that tumours seem to absorb more anticancer drugs when given in this way rather than in their regular form.
Traditional Chinese medicine has recipes (mixtures of herbs) for treating various infections, so it should not be surprising that extracts of some of these herbs can shut down production of HIV when tested in lab experiments. One of these herbs, commonly called green chiretta (Andrographis paniculata), is being tested under the brand name AndroVir as a treatment for HIV infection.
The American study ACTG 320 has been stopped because preliminary results were "impressive". (Note: as only limited information was released we cannot present a detailed report.) The study enrolled at least 1,156 volunteers (subjects) with an average of 88 CD4+ cells. Before entering the trial, subjects had all used AZT but not protease inhibitors nor had they taken 3TC for more than 1 week.
IL-2 is a chemical made by the immune system which helps T cells grow and fight infections. During the course of HIV infection, production of IL-2 falls, so some researchers think that supplements of IL-2 may be useful for PHAs. Doctors in Sydney, Australia, gave 5 subjects (whose CD4+ counts ranged between 200 and 500 cells), occasional infusions of IL-2 directly into a vein (intravenous, iv) at a dose of 12 million units/day for 5 days every 8 weeks.
In test tube experiments, the drug lobucavir has anti-herpes virus activity. Doctors in California tested several doses of this drug in 23 HIV-infected men who were also infected with CMV (but did not have CMV retinitis). The dose of 400 mg four times a day was taken orally and able to suppress the level of CMV to 1/10th its pre-study level. The drug appeared to be well tolerated and did not cause bone marrow damage. Lobucavir is made by Bristol-Myers Squibb
The introduction of protease inhibitors has been associated with increased CD4+ cell counts and decreased amounts of HIV in the blood of treated PHAs. As well, some PHAs given protease inhibitors have recovered from previously untreatable complications, such as
In other experiments on healthy subjects, researchers looked at the effect of delavirdine on blood levels of the three widely used protease inhibitors, saquinavir, indinavir and ritonavir
DMP 266 is a new drug that, like AZT, affects the HIV enzyme RT (reverse transcriptase). The drug is not related to AZT, but acts in a similar way to the drugs delavirdine and nevirapine. Doctors reported results on 30 subjects (4 female, 26 male) with an average CD4+ count of 240 cells and a viral load of 100,000 copies.
Doctors enrolled 320 subjects who had used AZT for at least 6 months but who had never taken protease inhibitors or 3TC. At the start of the study 50% of subjects had a CD4+ count of 15 cells and a viral load of 91,210 copies. Subjects received indinavir 2.4 g/day or a combination of AZT/3TC or all three drugs (triple therapy) at standard doses
For this study doctors in France recruited 144 HIV-infected subjects (33 female, 111 male), 50% of whom had AIDS. More than half the subjects had used AZT, ddC, ddI and/or 3TC while 33% had used d4T before entering the study. All subjects received antibiotics to prevent PCP and, in some cases, the life-threatening brain infection toxo (toxoplasmosis), as well as MAC (Mycobacterium avium complex).
A research team in France studied the effect of combination anti-HIV therapy on levels of different types of CD4+ cells in the blood. Doctors gave the subjects ritonavir alone for the first 15 days and then added AZT and ddC. Although the researchers enrolled 20 subjects, they only reported data on 8. At the start of the study, 4 of the 8 subjects had 166 cells
The protease inhibitor nelfinavir (ViraceptTM) has recently been studied in several clinical trials lasting for 6 months. In study 511, 297 subjects received either AZT/3TC with fake nelfinavir (placebo) or with either nelfinavir 500 mg or 750 mg three times daily. In study 506, 308 subjects received d4T with either nelfinavir (same doses as above) or placebo.
For this study doctors at Ottawa General Hospital recruited 43 HIV-infected subjects who had never before used protease inhibitors. Fifty percent of subjects had a CD4+ count of 300 cells. They received a combination of ritonavir and saquinavir
One small American study enrolled 30 male subjects who had an average of 79 CD4+ cells. About 90% had used AZT or related drugs for more than 3 years before entering this trial. All subjects had a viral load greater than 5,000 copies.
Although HIV infects CD4+ cells in the blood, most of the virus and 98% of CD4+ cells are in the lymph nodes/tissues. For a therapy to be effective, it must deal with HIV hiding in those sites. The tonsils are part of the network of lymph tissues, therefore several teams have been studying tonsils to uncover the effects of anti-HIV therapy
The good news, issues about viral load and questions about the new drugs The news presented at the 4th (American) Conference on Retroviruses and Opportunistic Infections was generally good. For the first time in the history of AIDS, treatments exist which can reduce, and help the immune system partially repair, the damage caused by HIV infection. In some cases, this has extended the lives of people with HIV/AIDS (PHAs).
Researchers in Mexico enrolled 28 adults (2 female, 26 male) who had suffered HIV-related weight loss. This problem occurred despite the use of AZT and related drugs (protease inhibitors were not available). None of the study volunteers had active, life-threatening infections at the time they entered the study, although they used drugs to suppress such infections before and during the trial.
Bacteria pneumonia (BP) is a complication that can occur in people with HIV/AIDS (PHAs). Some studies have found that PHAs taking the antibiotic Bactrim/Septra(R) to prevent PCP are also protected from BP. Doctors in Italy reviewed their hospital records to find out which of their HIV-infected patients taking Bactrim/Septra developed BP.
Highlights from the 4th Conference on Retroviruses and Opportunistic Infections
This information is designed to support, not replace, the relationship that exists between you and your doctor.