Important note: Information in this article was accurate in May 2003. The state of the art may have changed since the publication date.
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(RITA!) HIV Treatment Alerts - May 2003
HIV superinfection: it's real. HIV-infected patients have been cautioned against unprotected sex and sharing needles because of the possibility of contracting another, possibly more aggressive, strain of HIV. But until recently, there has been no definitive proof that this could happen. A recent study published in Nature 2002 Nov 28;420(6914):434-9 reported on a patient who began anti-HIV therapy shortly after being infected and then did 3 supervised treatment interruptions (STIs). During the first 2 STIs, the virus was controlled for a few months. However, during the third interruption, things started to go badly—virus levels rebounded quickly and T cells dropped. What happened? The researchers showed that the patient had been re-infected (or "superinfected") with another strain of HIV during the second STI; a time when the patient experienced a fever-associated illness after unprotected sex with an anonymous partner. Using a variety of techniques, the researchers showed that this new strain was distinct from the original strain.
A second study by a different group of researchers described a patient who initially was infected with a strain of drug-resistant HIV but not put on anti-HIV drugs because of his low viral load (about 2400) and high T cell count (about 800). Four months later, however, the patient's viral load rose to almost 200,000 and his T cells fell to less than 300. These changes coincided with the presence of a new strain of HIV acquired by the patient 4 months after the first HIV infection. The report is published in the May 2 issue of the journal AIDS 2003 May 2;17(7):F11-6.
These findings raise some important issues in HIV treatment. First, is superinfection a real issue for patients with HIV or does it just occur in rare, isolated cases? Studies done in monkeys have shown that superinfection happens infrequently. Second, what does this mean for the development of a vaccine? Researchers must design a vaccine that protects against multiple strains of HIV because a vaccine that protects against just one strain may be useless if superinfection can occur. Third, is delaying treatment or taking STIs truly safe since being off anti-HIV medication may allow another virus to infect patients? Until more is known about the effects of HIV superinfection on patient health and treatment options, practicing safer sex and not sharing needles may be more important than ever for people with HIV.
Kaposi's sarcoma update. Kaposi's sarcoma (KS) is the most common cancer associated with HIV infection. While cases of KS have dropped in the US since the wide use of anti-HIV therapy, KS can be fatal. Symptoms such as pain, edema (fluid retention and swelling), and disfiguring lesions, can really affect a patient's quality of life. In the past, patients were typically treated with special drugs such as liposomal anthracyclines or paclitaxel. These drugs help control the cancer, but patients tend to relapse. In a recent study published in the J Clin Oncol 2002 Aug 1;20(15):3236-41, researchers report that low-dose oral etoposide given daily for 7 consecutive days (with 14-day breaks in between) is very effective for treating KS in patients who relapse or do not respond to standard chemotherapy. Thirteen of 36 patients responded to etoposide therapy and 1 patient had a complete remission. Side effects of the treatment included mild to moderate achiness, pain, discomfort, nausea, vomiting, decreased levels of certain blood cells, and anemia. A few patients experienced some of these more severely. Those patients who responded to therapy reported pain relief and an improved quality of life. These results are encouraging for patients with KS who have not responded to chemotherapy or whose KS has relapsed. Also, in less developed countries where KS is still widespread, low dose oral etoposide provides an effective, oral treatment.
Increased risk of diabetes in women with HIV. A recent study published in J Acquir Immune Defic Syndr 2003 Mar 1;32(3):298-302 investigated the incidence of diabetes mellitus in HIV-infected women. The researchers reported that women taking protease inhibitors were almost 3 times more likely to develop diabetes. Not surprisingly, women who were obese or older were also at an increased risk for developing diabetes, regardless of HIV status or treatment regimen. In fact, women who were morbidly obese were more than 4 times as likely to develop diabetes. A change in T cell count or viral load did not make a woman more likely to develop diabetes, nor did weight gain during protease inhibitor treatment. The authors concluded that these findings should not discourage patients from taking protease inhibitors because of the benefits of therapy. Instead, patients taking protease inhibitors who are at risk for diabetes, such as those who are overweight or older, should be routinely screened for the development of diabetes.
Take your vitamins. Not gaining enough weight or actually losing weight during pregnancy is a potential risk for HIV-infected women because of opportunistic infections, decreased appetite, and hormonal changes. Low weight gain during pregnancy can cause babies to be born premature or underdeveloped. Two recent studies by the same group of researchers stress the importance of taking multivitamin supplements during pregnancy and while breastfeeding. The studies were done in an African country called Tanzania. Infant death and disease from severe diarrhea or respiratory infection are very common in this part of the world.
The first study, published in the Am J Clin Nutr 2002 Nov;76(5):1082-90 showed that a daily multivitamin supplement (including vitamins B, C, and E) helped pregnant, HIV-infected women maintain a healthier weight during pregnancy. In fact, women taking a multivitamin supplement gained an average of 10.5 ounces (less than 1 pound) during the 3rd trimester compared to woman taking a placebo. The second study, published in Clin Infect Dis 2003 Apr 15;36(8):1053-62 showed that use of a daily multivitamin supplement (including vitamins B, C, and E) by HIV-infected women during pregnancy and breastfeeding has a positive effect on their baby's health. Babies born to mothers who took multivitamin supplements during pregnancy and while breastfeeding were less likely to experience diarrhea. These babies also had higher T cell counts, whether they were infected with HIV or not. One caution to consider is that the use of vitamin A supplements by pregnant or breastfeeding women increases the chance of transmitting HIV from mother to child. However, giving vitamin A supplements directly to children is beneficial. These findings suggest that vitamin A supplements only be given to children and HIV-negative pregnant or breastfeeding women.
In the US and other countries where HIV therapy is widely available, giving anti-HIV therapy (such as Retrovir) during pregnancy is highly effective at preventing mother-to-child HIV transmission. Also, breastfeeding is not recommended because breast milk can transmit HIV to newborns.
Brain diseases persist. A review of autopsy reports from HIV-infected patients showed that cases of HIV encephalopathy, a brain disease that can cause structural alterations, are increasing. The study, published in the J Acquir Immune Defic Syndr 2002 Oct 1;31(2):171-7 describes data collected from HIV-infected patients who died between 1985 and 1999. Opportunistic infections of the brain, such as cytomegalovirus (CMV), toxoplasmosis, cryptococcosis, and lymphoma have decreased over time. Cases of severe forms of HIV encephalopathy have also decreased, but the incidence of mild and moderate forms of the disease has increased, especially after the introduction of combination anti-HIV therapy (also called "HAART") in 1996. Patients on HAART are living longer, which may give HIV more of an opportunity to cause problems in the brain. Researchers speculate that HAART may lessen the severity of HIV-related brain diseases by decreasing a patient's viral load. Unfortunately, these agents probably have a limited effect on fully preventing the damage.
Bones and HIV. The incidence of osteonecrosis, a condition in which part of the bone dies because of low blood supply, is on the rise in people infected with HIV. In the general population, males are 8 times more likely to develop osteonecrosis, specifically males between 20 and 50 years old—a group well-represented in the HIV-infected population. Osteonecrosis occurs most frequently in the hip but can affect other weight-bearing joints. As reported in the Ann Intern Med 2002 Jul 2;137(1):17-25, asymptomatic HIV+ patients were more than 4 times as likely to have osteonecrosis in their hip bones compared to people with normal immune systems, as shown by MRI scans of the hip. Risk factors include the use of lipid-lowering drugs, testosterone, or corticosteroids; a history of bodybuilding; or excessive alcohol consumption. Why HIV-infected individuals are at an increased risk for osteonecrosis is not known. A recent article in the journal AIDS 2003 Jan 3;17(1):1-9 reviews the relationship between HIV and osteonecrosis and the contribution of anti-HIV drugs. Some studies have suggested that protease inhibitors may cause osteonecrosis, but no conclusions can be drawn for sure. In addition, protease inhibitors have been shown to increase lipids, thus requiring the use of lipid-lowering drugs. Also, combination anti-HIV therapy is associated with inflammation of the pancreas, increased levels of uric acid in the blood (hyperuricemia), decreased number of bone-making cells, and inflammation of the bone. All of these conditions are risk factors for osteonecrosis.
Routine screening for osteonecrosis in HIV-infected individuals is not currently recommended, though it should be considered in patients experiencing joint pain. X-rays are an inexpensive way to screen for osteonecrosis, but often miss the disease in its early stages. An MRI is the best way to diagnosis osteonecrosis and should be done in patients suspected of having osteonecrosis but whose x-ray shows no problems. If osteonecrosis is detected early, it can usually be reversed if risk factors are minimized (for example, avoiding high alcohol consumption, the use of certain medications, and weight bearing activities on the affected joint). Advanced osteonecrosis frequently requires surgery and possibly total joint replacement.
Will the HepA vaccine work for you? Infection with hepatitis A (HepA) virus is a significant risk for people with HIV. Acute HepA infection can be serious and potentially increase a patient's HIV viral load. While a HepA vaccine is available, some vaccines are not effective in many HIV-infected people. In addition, some vaccines can temporarily raise a person's HIV viral load. A recent study published in the J Infect Dis 2003 Apr 15;187(8):1327-31 examined HIV-infected patients who received 2 doses of the HepA vaccine or a placebo 6 months apart. Nine months after the first dose of vaccine was given, 52% of these patients showed antibodies against HepA. The study also showed that a patient's T cell count prior to getting the vaccine was the most important predictor of whether the patient would respond to the vaccine. For example, 68% of patients with T cell counts over 200 experienced seroconversion compared to 9% of patients with T cell counts under 200. Importantly, viral load was not affected by the vaccine. Overall, the vaccine was well tolerated and the most common side effect was mild soreness at the injection site. Unfortunately, the HepA vaccine may not fully protect against the HepA virus. These results also raise the question of whether to delay immunization until T cell counts are above 500.
HIV and hepatitis B: a deadly combination. The vast majority of adults recover spontaneously from acute hepatitis B (HepB) virus infection, but chronic HepB infection can develop. Co-infection with HIV and HepB occurs frequently, and HIV increases the chances of developing chronic HepB infection. In a study published in Lancet 2002 Dec 14;360(9349):1921-6, researchers report that people infected with both viruses are more than 8 times more likely to die of liver disease compared to people infected with just HIV, and almost 19 times more likely to die compared to people infected with only HepB. Death rates are highest among co-infected patients with low T cell counts. Not surprisingly, excessive alcohol consumption (usually considered to be more than 2 drinks per day) also increases the risk of dying from liver disease. The number of deaths from liver disease rose significantly after 1996, which coincides with the introduction of combination anti-HIV therapy (also called "HAART"). Drug-related liver damage may be partly responsible. The researchers also speculate that since HAART enables HIV-infected patients to live longer, liver disease has more time to develop. Adding to the problems, HAART enhances immune system reactions, which may accelerate liver damage. Because HepB infection frequently goes undetected, preventing and identifying HepB infection in people with HIV is a major challenge facing healthcare providers.
FDA Bits
Viread and kidney problems. No anti-HIV drug is perfect. With all anti-HIV drugs, news surfaces eventually about side effects and toxicities. Viread is no exception. Viread is a nucleotide reverse transcriptase inhibitor that can fight HIV, as well as hepatitis B. Since December 2002, several reports have described kidney problems in patients taking Viread as part of their anti-HIV drug combination. (The most recent report, about 3 new cases, was published in the April 15 issue of Clin Infect Dis 2003 Apr 15;36(8):1070-3. Viread is cleared from the body by the kidneys, unlike most other anti-HIV drugs that are cleared by the liver. The kidney problems seen so far are similar to a disease known as "Fanconi Syndrome." Symptoms may include elevated levels in the blood of a natural substance known as creatinine. Other symptoms may include extreme thirst, frequent urination with watery urine, confusion, and muscle weakness. In several patients, the kidney problems went away after stopping Viread. This problem is not believed to be widespread in patients who take Viread, but careful monitoring of kidney function by healthcare providers, as well as a familiarity with symptoms, is recommended.
Atazanavir expanded access. Atazanavir is an experimental protease inhibitor that is currently being considered for approval by the US Food and Drug Administration. The drug is taken once a day and does not raise blood fat levels like some other protease inhibitors. The drug may also be an option for some treatment-experienced patients with drug-resistant HIV. Until the drug is approved, an expanded access program is available for patients who may need atazanavir because of drug resistance or other problems with available drugs. Your doctor or healthcare provider can call 877.726.7327 for more information.
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Copyright © 2003 - Research Initiative Treatment Action (RITA!). Reproduced with permission. RITA! is published by The Center for AIDS. Contact Thomas Gegeny, MS, ELS, Editor, RITA! for permission to reproduce RITA!. tom@centerforaids.org. http://www.centerforaids.org
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