Longer Drug Therapy Helps Infants Ward Off HIV Infection, Cancer Risk Soars in HIV-Infected Persons, Darunavir Linked to Serious Liver Adverse Effects

July 1, 2008

Infants who receive 3 additional months of treatment with the drug nevirapine are less likely to be infected with HIV by their mothers through breast-feeding (Emery G. Reuters. June 4, 2008).

Longer Drug Therapy Helps Infants Ward Off HIV Infection
Infants who receive 3 additional months of treatment with the drug nevirapine are less likely to be infected with HIV by their mothers through breast-feeding (Emery G. Reuters. June 4, 2008).

In one study of thousands of newborns in Malawi, it was found that adding 14 weeks of treatment with nevirapine to the standard therapy––1 dose of nevirapine plus a week of treatment with zidovudine––halved the infection rate at 9 months to 5.2%. Adding zidovudine to nevirapine for the additional 14 weeks offered no additional benefit and may have caused more adverse effects.

The second study, based in Zambia, was designed to see whether early weaning of babies of HIV-positive mothers lowered the risk of transmission. Instead, it found little benefit. The research team, led by Dr Louise Kuhn of Columbia University, New York, studied 481 babies whose mothers weaned them at 4 months. More than 68% of these babies were uninfected at 2 years compared with 64% whose mothers were encouraged to breast-feed as long as they wanted.

However, among babies already infected by age 4 months whose mothers had been encouraged to stop breast-feeding, the risk of death dramatically increased to nearly 74% before age 2 compared with 55% among babies whose mothers had been told to keep nursing. Preliminary results from this study prompted the World Health Organization to change its breast-feeding recommendations for women in developing countries.

According to Lynne Mofenson, the National Institute of Child Health and Human Development's project (Bethesda, Md) officer for both studies, the results "say you should exclusively breast-feed the baby and you should give the baby antiretroviral drugs for at least 14 weeks." The institute is now looking at whether longer drug treatment will be even more beneficial.

The results of the two studies will be published in the New England Journal of Medicine (Kumwenda NI, Hoover DR, Mofenson LM, et al. Extended antiretroviral prophylaxis to reduce breast-milk HIV-1 transmission. N Engl J Med. 2008 July 10; [Epub ahead of print]. Kuhn L, Aldrovandi GM, Sinkala M, et al. Effects of early, abrupt weaning for HIV-free survival of children in Zambia. N Engl J Med. 2008 July 10; [Epub ahead of print]). [CDC HIV/Hepatitis/STD/TB Prevention News Update, Friday, June 6, 2008]

Cancer Risk Soars in HIV-Infected Persons
According to a new study, people infected with HIV are at a much higher risk for many cancers, especially anal cancer. The study focused on trends from 1992 to 2003 and involved 54,780 HIV-positive men and women (Dunham W. Reuters. May 21, 2008).

"The study was done because we all know that now people with HIV are living longer, and HIV is looking more like a chronic disease. So we wanted to look at one of the other very large chronic killers in America, cancer," said Dr Pragna Patel, a CDC researcher who led the study.

By 2003, anal cancer had become 59 times more common among HIV-infected persons than among the general population. In addition, Hodgkin disease was 18 times more common, liver cancer 7 times more common, lung cancer 3.6 times more common, melanoma and throat cancer both 3 times more common, and colorectal cancer 2.4 times more common. According to Patel, "Most significant was the finding of anal cancer being so elevated even in the HAART era." She said that multiple factors may be involved, but the increased risk may be linked to the spread of human papillomavirus (HPV) through anal sex between men. HPV is known to cause anal cancer.

Patel added that doctors who care for HIV-infected persons should be aware of this increased risk for a range of cancer types and consider screening. The study is the largest analysis of cancer trends among HIV-infected persons in the United States ever done, she noted.

Some cancers, such as Kaposi sarcoma and non-Hodgkin lymphoma, have long been associated with HIV infection. The study showed that these 2 types of cancer became relatively less common among this group.

The study also found that HIV-infected people had a small reduction in risk for prostate cancer. The researchers said this may have occurred because HIV-infected men are more likely to have lower testosterone levels, which could be protective against prostate cancer. The results of the study were published in the Annals of Internal Medicine (Patel P, Hanson DL, Sullivan PS, et al. Incidence of types of cancer among HIV-infected persons compared with the general population in the United States, 1992-2003. Ann Intern Med. 2008;148:728-736). [CDC HIV/Hepatitis/STD/TB Prevention News Update, Thursday, May 22, 2008]

Health Canada Links Darunavir to Serious Liver Adverse Effects
Canadian health officials and Tibotec, a division of drug maker Janssen–Ortho, are advising patients who take darunavir (Prezista) that serious liver adverse effects have been linked to the drug. Darunavir is used, in combination with ritonavir and other HIV drugs, for patients in whom other antiretroviral therapy has failed (Canadian Press. May 15, 2008).

Hepatitis or inflammation of the liver developed in 0.5% of darunavir patients studied in clinical trials. Since the drug came to market, there have been 13 reported cases of hepatitis in patients taking darunavir; 2 died. In addition, there were 25 reported cases of other liver problems in patients taking darunavir from mid-2006 to the end of 2007; 14 of these patients died.

It is not known whether darunavir contributed to these adverse events and deaths or whether they were caused by other medical problems or medications taken by the patients. However, Health Canada said that the patients involved all had advanced HIV disease, were taking other medications, or had illnesses such as hepatitis B or C. Patients with liver problems are at greater risk for darunavir adverse effects, the warning says.

Health Canada urges patients taking darunavir to contact their physician immediately if they experience any of the following symptoms: dark urine, yellowing of the skin, abdominal pain (especially on the right side bellow the ribs), general itchiness, decreased appetite, nausea, vomiting, or fatigue. Patients should not stop taking darunavir without first consulting their physician or pharmacist. More information is available at www.janssen-ortho.com/JOI/pdf_files/Prezista_PC_E.pdf [CDC HIV/Hepatitis/STD/TB Prevention News Update, Friday, May 16, 2008]

Adverse Effects of Antiretroviral Therapy Differ by Race and Sex
A new study observed significant differences in specific adverse events according to sex and race among HIV-infected patients starting antiretroviral therapy (Reuters. April 30, 2008). However, Dr Ellen M. Tedaldi from Temple University School of Medicine, Philadelphia, and colleagues found no differences in the overall rate of adverse events, death from any cause, or treatment withdrawal rates due to drug toxicity.

The researchers compared the frequency and types of adverse effects by sex and race in 1301 patients in an antiretroviral therapy initiation trial. This study population included 701 blacks, 225 Latinos, and 273 women.

During the average 5-year follow-up, there were 409 grade 4 adverse events, grade 4 being the most severe, for a rate of 8.9 per person per 100 years. There were 176 deaths, a rate of 3.0 per person per 100 years; and 523 antiretroviral therapy withdrawals because of toxicity, a rate of 13 per person per 100 years.

Black patients reported cardiovascular and kidney adverse events 2.64 and 3.83 times more frequently, respectively, than white patients or participants of any other race. The researchers noted that this finding is consistent with greater rates of heart disease, diabetes, and kidney disease found in the general black population.

Rates of serious psychiatric events were 2.45 times higher in black men than in men of other races. "It is likely that grade 4 psychiatric adverse events represent a constellation of factors that include psychosocial and biologic associations," suggested Tedaldi and colleagues. This could reflect undiagnosed mental illness or the CNS effects of HIV infection, they noted. In addition, women had a 2.34-fold higher risk of grade 4 anemia than did men, which was "not unexpected" given that the women were predominantly premenopausal and African American.

The researchers concluded that the results "could inform HIV-treating clinicians about particular issues to consider in the selection of antiretroviral regimens for diverse populations." Results of the study were published in the Journal of Acquired Immune Deficiency Syndromes (Tedaldi EM, Absalon J, Thomas AJ, et al. Ethnicity, race and gender: differences in serious adverse events among participants in an antiretroviral initiation trial: results of CPCRA 058 (FIRST Study). J Acquir Immune Defic Syndr. 2008;47:441-448).

Niche Pharmacies Fill Need
Small niche pharmacies are providing medications, advice, and resources to HIV/AIDS patients in an effort to combine the services of specialty mail-order pharmacies with the personal attention and convenience of a neighborhood drug store (Feldstein MJ. St. Louis Post-Dispatch. May 21, 2008). For many traditional retail pharmacies, selling these medications does not attract enough business to justify the expensive inventory and specially trained staff.

To attract enough patients, niche retail pharmacies specialize in the condition, locate in neighborhoods with higher percentages of HIV-positive patients, and advertise their presence to physicians and advocates. Pharmacists say patients appreciate the special attention, such as quick home deliveries and the privacy of a smaller pharmacy.

The marriage of CVS Corp. and Caremark Inc. joined a retail pharmacy industry with a pharmacy benefit management business. This created a specialty pharmacy called CarePlus, formerly known as PharmaCare, which operates small retail stores as well as mail-order businesses. One such pharmacy can be found in the Central West End section of St Louis.

CarePlus and BioScrip are 2 mail-order specialty pharmacies with local retail outposts that focus on HIV/AIDS treatment. Medicine Shoppe and Walgreens are 2 traditional retail stores that have added specialized services for these same patients. Mail-order rivals, such as Express Scripts Inc. of north St Louis County, think such niche retailers will not be as successful as they are over the long term. According to Steve Miller, vice president of pharmacy for Express Scripts, having prescriptions mailed is more convenient and phone counseling can be more private than a retail pharmacy can offer. [CDC HIV/Hepatitis/STD/TB Prevention News Update, Friday, May 23, 2008]

University of Alabama-Birmingham Puts HIV Infection in Focus
Findings from a new study show most HIV infections can be traced to a single virus that has managed to penetrate the body's natural defenses (Parks D. Birmingham News. May 20, 2008).

Lead investigator George M. Shaw of the University of Alabama-Birmingham and colleagues analyzed blood from 102 people recently infected with HIV. Using the latest techniques for genetically analyzing viruses, the researchers were able to count generations. They found that 76% of the cases could be linked to a single virus, and the remaining 24% could be tracked back to 2 to 5 viruses. In contrast, other sexually transmitted diseases, such as syphilis and gonorrhea, mount a massive attack. "They just all come across, 10, 20, 100, 200 bacteria or spirochetes," said Shaw.

The study shows that it takes just 1 HIV virus to wreak havoc. "In the vast majority of cases, a single virus has gone across the sexual mucosa, and that virus has infected a cell," Shaw explained. "That cell then makes a lot of virus. Now you just have a firestorm of HIV replication in the next couple of weeks. Very quickly the person is populated by millions of viruses."

Researchers have long known that it typically takes several exposures for a person to become infected with HIV, and the study explains why HIV's transmission is so inefficient. It also points to why condoms are effective in preventing HIV infection. A condom presents a barrier method that has the potential to stop all viruses. Microbicides, which do not stop all viruses, have been less effective. "It's shining a light on the HIV transmission process," said Shaw. "And it's providing some benchmarks and genetic clarity to people who do vaccine studies in both primates and humans. It will help them understand if their vaccine is working, and if it's not working, why it's not working."

The results of the study were published in the Proceedings of the National Academy of Sciences of the United States of America (Keele BF, Giorgi EE, Salazar-Gonzalez JF, et al. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci U S A. 2008;105:7552-7557). [CDC HIV/Hepatitis/STD/TB Prevention News Update, Monday, June 9, 2008