Updates

By Carol A. Kemper, MD, FACP, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases; Santa Clara Valley Medical Center, Section Editor, Updates; Section Editor, HIV, is Associate Editor for Infectious Disease Alert.

Deal Struck for Lower Cost HIV Treatment

New York Times, January 12, 2006, page A11.

The Clinton Foundation announced the successful conclusion of negotiations with several pharmaceutical companies to provide lower cost HIV testing and treatment to poorer countries. Four companies—3 from India and 1 from South Africa— have agreed to provide nevirapine and abacavir (at $USD 240 and $447 per patient per year, respectively), provided that certain conditions are met on an ongoing basis. These include the receipt of large, advance orders for drug, with regular payments, and a dependable supply of materials. Cipla, an Indian pharmaceutical company, indicated the cost of nevirapine would increase by 11% if orders were lower than expected.

Demand should sadly not be a problem. Four companies from the United States, China, and India also agreed to provide lower cost HIV testing, ranging from $.49 to $.65 (down from about one dollar). It is estimated that 90% of those infected with HIV around the world—about 36 million people—are unaware of their infection. Low cost tests for detection are the first step to providing treatment for those who need it.

Risk of Fetal Death Increased with HAART

Suy A, et al. Increased Risk of Pre-Eclampsia and Fetal Death in HIV-Infected Pregnant Women Receiving Highly Active Antiretroviral Therapy. AIDS. 2006;20:59-66.

Earlier reports suggested that lactic acidosis and premature delivery are more common in HIV-positive pregnant women receiving antiretroviral therapy. These authors have found an increased risk for pre-eclampsia and fetal death in pregnant HIV-positive women receiving HAART. While rates per 1000 deliveries remained stable in HIV-negative women between the period of 1985-2000 to 2001-2003, rates per 1000 deliveries in HIV-positive women increased from 0 to 109.8 for pre-eclampsia, and from 7.7 to 61 for fetal death for the same time periods. Additional risk factors for both groups included multiple gestations, multiparity, and tobacco use.

Interestingly, in HIV-positive women, the use of HAART before pregnancy was also associated with a significantly higher risk of pre-eclampsia and fetal death. While the risk of HAART therapy administered prior to (adjusted OR 5.6, 95% CI, 1.8-18.1) versus during (adjusted OR 4.9, 95% CI 2.4-10.1) pregnancy appeared similar, it was not clear from this analysis to what degree the effect of cumulative therapy was on those risks. Whether it is possible to identify women at greater risk, such as those with lipodystrophy, is not known. HIV-positive women who are pregnant or desirous of pregnancy should be counseled regarding this additional threat.

Viread—The New Safe Sex Pill

Los Angeles Times, January 3, 2006.

This article confirms what HIV clinicians—at least on the West Coast—have been facing for more than a year. Over the past few months, I have seen 5 newly diagnosed gay men, two with acute primary HIV infection, and two with positive syphilis titers; all 5 acquired their infection during weekend "clubbing" in San Francisco. All 5 reported "weekend" methamphetamine use, and they all believed they had good control of their drug use. Over the new few months, it became clearer that all of them used more frequently, and at least for 2 of them, their meth use had spun out of control. Two lost their jobs.

Meet the new face of HIV. New infections in gay and bisexual men having sex with men (MSM) increased 8% last year, and syphilis rates have increased 29%. San Francisco County reported 17 cases of syphilis diagnosed in 2003; last year the rate was expected to top 1700 cases.

Blame it on the new "cocktail." MSM are increasingly downing combinations of viread, viagra, ecstasy, and methamphetamines—the former in the hope of preventing HIV transmission, and the latter 2 to "heighten" the sexual experience. My gay friends tell me the clubs are filled on weekends with MSM; coupling occurs dozens of times in one night; bowls of condoms are readily available but ignored by half. Surveys performed at recent gay pride events found that 7% of gay men had taken an antiretroviral agent before engaging in risky sexual behavior. Other data that we collected from major urban areas on the West Coast found that about 40% of sexually active MSM engaged in unprotected oral or anal sex with at least one partner in the previous 3 months, and 25% had failed to disclose their HIV status.

Viread is a perfect drug for use—abuse—in these circumstances because it is remarkably well tolerated and has a long half-life (12-14.4 hrs). Viread is currently recommended, in combination with other agents, such as emtriva and efavirenz, for post-exposure prophylaxis (PEP) for percutaneous exposure, where anti-retroviral therapy is increasingly believed to provide some protection against high risk needlesticks. And, preliminary data from 2 CDC studies suggest that viread may reduce sexual transmission of HIV when taken preventatively.

The gay community has extended this research to real world practice, thinking that if it can reduce transmission for one high risk exposure, why not multiple? If post-exposure prophylaxis provides som protection, why not pre-exposure exposure? Even if viread is successful in reducing the risk of sexual transmission to a similar degree as that estimated for a 4-week regimen of PEP for percutaneous exposure, back of the envelope calculations suggest, with a minimum of 100 exposures per year, this practice will result in a rate of annual infection somewhere between 1 to 10%. Early on, the gay community could not be held accountable for the spread of HIV, and over the years many health care providers have sought ways to better communicate the risks to their patients and modulate risky behavior. Sadly, these MSM know exactly what they are doing.

Hepatitis in a Traveler Receiving Atovaquone/Proguanil

Grieshaber M, et al. Acute Hepatitis and Atovaquone/Proguanil. J Travel Med. 2005;12:289-290.

This brief report describes the occurrence of acute hepatitis possibly related to the administration of atovaquone/proguanil (AP) for malaria prophylaxis. A 31-year previously healthy man took AP for 25 days while traveling in Southern Africa. About 2 weeks after his return, he developed flu-like symptoms, with anorexia and jaundice. Serologies for hepatitis viruses A, B, C, E, EBV, cytomegalovirus, schistosoma, and rickettsia; smears for malaria; and studies for auto-immune hepatitis were all negative. AP was discontinued, and within 6 to 8 weeks, the liver function tests normalized. The authors tentatively diagnosed a drug related hepatitis. Elevations in liver function studies have been reported during treatment of active malaria with AP. While the reported incidence of elevations in alkaline phosphatase and transaminases during AP treatment of active malaria varies, they may occur in up to 2-4% of cases. And, elevations in transaminases greater than 5 times the upper limit of normal occur in 4-6% of patients being treated with atovaquone for pneumocystosis, although only 2% of cases resulted in dose-limiting toxicity. While clinical hepatitis and jaundice during AP malaria prophylaxis has not been previously reported, a drug-induced hepatitis seems plausible in this case.

Bovine TB threatens Minnesota

Pro-MED-mail post, December 10, 2005; www.promedmail.org

My home state of Minnesota joins three other states that have lost their TB-free status for cattle, including Michigan, Texas and New Mexico. Last winter, the United States Department of Agriculture announced the discovery of bovine TB in a cow in Roseau County, near the Canadian border. Forty-two herds of cattle were quarantined, 4 of which were found to be infected (6 are still being tested) leading to the destruction of more than 4000 cattle in 2 counties. Ranchers in Minnesota will now be required to pay for mandatory testing of all cattle shipped outstate to feedlots, for slaughter, or for breeding.

Blame it on the insidious spread of TB among the white tailed deer populations in the Northwest. Mycobacterium tuberculosis vs bovine can infect a wide range of warm-blooded vertebrates, where it is generally transmitted through nose-to-nose contact or oral/nasal secretions. The United States TB eradication program has been widely successful in eradicating bovine TB in the United States, except in a few states where isolated animals have come in contact with infected wildlife. Michigan has been especially hard hit, with an estimated 150 million dollar loss in cattle sales last year. The problem has become so severe, that adjacent Indiana has considered fencing in its northern border to keep the deer population from migrating south.

Most TB in cattle is found in the lungs and in lymph nodes, and can readily be spotted at slaughter. There is little risk of contagion, or threat to humans caring for the animals, although disease can be transmitted through ingestion of unpasteurized mild products and undercooked meat or, rarely, close contact with nasal secretions.