Battle Against Virus Shows Signs of Progress, Hispanics Respond Poorly to Hepatitis C Treatment, Litigation Harmful in HIV Prevention

March 13, 2009

New data from UNAIDS show that several African countries with a high HIV prevalence have made significant gains in preventing new infections.

Battle Against Virus Shows Signs of Progress
New data from UNAIDS show that several African countries with a high HIV prevalence have made significant gains in preventing new infections. The agency’s latest report says changes in sexual behavior in Rwanda and Zimbabwe have led to a drop in new HIV infections, and young people in Burkina Faso, Ethiopia, Ghana, Malawi, Uganda, and Zambia are delaying the start of sexual activity (Kharsany Z. Inter Press Service. January 10, 2009).

Across the continent, AIDS campaigners are calling for people to assess the local situation to determine what is driving the epidemic and then the best way to act on this information. Examples of “knowing your epidemic” include the following: 

• In Rwanda, health officials have made a concerted effort to involve male partners in the prevention of mother-to-child HIV transmission. “When I look back to 2004, we just had 6% of male partners accompanying their wives to checkup clinics, but today we have figures as high as 64%,” said Anita Asilmwe of the country’s National AIDS Control Commission. Government data show nearly 90% of children born to HIV-positive mothers are uninfected, compared with less than 40% 2 years ago.

• In Kenya, HIV prevention messages are shifting from overall AIDS awareness-more than 90% of Kenyans are aware of HIV/AIDS-to addressing specific at-risk groups. Omu Anzala, director of the Kenya AIDS Vaccine Initiative, said these include “people who sell sex, people who buy sex, regardless of the kind of sex they buy.”

However, in South Africa, home to the world’s largest HIV/AIDS caseload, prevention campaigns remain static. The government still takes a “standardized cookie-cutter approach to prevention,” said Quarraisha Abdool Karim, associate scientific director at the Centre for the AIDS Programme of Research in South Africa. “We are not targeting our intervention. We do not have adequate coverage of interventions that work; knowledge of HIV status and personal risk is low,” Karim said. [CDC HIV/Hepatitis/STD/TB Prevention News Update, Friday, January 16, 2009]

Hispanics Respond Poorly to Hepatitis C Treatment
Latinos appear to respond less well than whites to the current standard drug therapy for hepatitis C, a new multicenter study indicates (Tasker F. Miami Herald. January 14, 2009). The results are similar to those of a 2006 study that found blacks with hepatitis C also respond less well to treatment.

The open-label, nonrandomized, prospective study evaluated 269 Hispanics and 300 non-Hispanic whites with hepatitis C who received standard doses of peginterferon alfa-2a (Pegasys) with ribavirin for 48 weeks. Rates of sustained virological response in patients infected with hepatitis C virus genotype 1 were higher among whites than Latinos (49% vs 34%). “There’s something different about their [Latinos’] makeup, either genetic or immunological, that makes the virus respond less to the medication,” said Dr Lennox Jeffers, professor of medicine at the University of Miami and a study coauthor. “We don’t know the exact mechanism.”

Jeffers said Latinos have been underrepresented in hepatitis C studies. However, more Latinos are enrolled in new studies in which protease inhibitors, such as telapravir or bocepravir, are added to standard hepatitis C drug regimens.

Dr Paul Martin, chief of hepatology at the University of Miami Medical School and another study coauthor, said adding protease inhibitors will increase overall cure rates to 60% within 2 years, and other new drugs are expected to increase cure rates to 70% within 3 to 5 years. Whether Latinos and blacks will respond to those therapies as well as whites do is unknown.

The report of the study was published in the New England Journal of Medicine (Rodriguez-Torres M, Jeffers LJ, Sheikh MY, et al; Latino Study Group. Peginterferon alfa-2a and ribavirin in Latino and non-Latino whites with hepatitis C. N Engl J Med. 2009;360:257-267). [CDC HIV/Hepatitis/STD/TB Prevention News Update, Friday, January 16, 2009]

Litigation Harmful in HIV Prevention
HIV-infected persons who unintentionally transmit the infection to others should not be criminally charged, according to Dr Mark Wainberg, former president of the International AIDS Society and director of the McGill AIDS Center. In a recent editorial, Wainberg said that while people who knowingly or maliciously transmit HIV should be criminally charged, charging those who do not transmit the virus deliberately increases the stigma of HIV, and fewer people may seek testing as a result (Hayes J. Hamilton Spectator. January 15, 2009).

“We want to create incentives to get tested,” Wainberg said. “There’s every reason to want to encourage broad-scale testing. But criminalizing, which stigmatizes HIV positivity, is discouraging.” Ronald Johnson, deputy director of the AIDS Action Council in Washington, DC, agreed that prosecuting such cases is counterproductive. “The goal is to get everyone to know his or her status,” he said. “Because current laws mean that if I don’t know my status, and I don’t get tested, then I wouldn’t be subject to any laws.”

Current Canadian laws are based on a 1998 Supreme Court decision that HIV-infected persons who do not disclose their HIV status to partners before having sexual relations are committing assault. Johnson said that because of that ruling, more arrests are being made. A Hamilton man has been charged with 11 counts of aggravated sexual assault and 2 counts of first-degree murder because he did not reveal his HIV-positive status to his sexual partners.

“Ultimately, people who have sexual relations have to assume individual responsibility,” Wainberg said. “It cannot be evaded.” These findings were reported in Retrovirology (Wainberg MA. HIV transmission should be decriminalized: HIV prevention programs depend on it. Retrovirology. 2008;5:108). [CDC HIV/Hepatitis/STD/TB Prevention News Update, Thursday, January 15, 2009]

Guidelines for New, Faster TB Test
The CDC has released new guidelines that call for nucleic acid amplification (NAA) testing to be performed on patients with suspected pulmonary tuberculosis (TB). The agency’s recommendations reflect the increasing use of NAA tests in diagnosing the bacterial infection. NAA test guidelines were last updated in 2000 (United Press International. January 15, 2009).

Last summer, the CDC and the Association of Public Health Laboratories convened a panel to review existing guidelines and make recommendations to incorporate NAA tests into standard practice. NAA testing can confirm pulmonary TB weeks faster than conventional testing, which includes acid-fast bacilli smear and culture for Mycobacterium tuberculosis. The new guidelines include revised procedures for testing and for interpreting results and provide advice for clinicians to ensure accuracy and cost savings in interpretation of NAA test results.

The recommendations, “Updated Guidelines for the Use of Nucleic Acid Amplification Tests in the Diagnosis of Tuberculosis” were published in the Morbidity and Mortality Weekly Report (2009;58:7-10). [CDC HIV/Hepatitis/STD/TB Prevention News Update, Friday, January 16, 2009]

Study May Predict Whether Hepatitis C Drugs Will Work
By analyzing variations in the RNA chains composing hepatitis C virus (HCV), physicians can predict which patients will respond to standard treatment with pegylated interferon and ribavirin, according to a new study (Steenhuysen J. Reuters. December 22, 2008). Treatment typically lasts about a year, during which patients can feel as if they have influenza.

“This is a very difficult therapy to take,” said study coauthor John Tavis, a professor of molecular and microbiology at Saint Louis University in St Louis. “If you can identify those patients who aren’t going to respond anyways because they’ve got a strain that is highly resistant to the drug, then you just don’t treat those patients and you save them $20,000 to $30,000 in medical bills just from drugs alone, not to mention the side effects.”

Tavis and colleagues studied HCV RNA chains to find patterns that could explain why only about half of patients respond to the treatment. Using a mathematical formula, the team found a specific pattern of changes called “covariance networks” that differed by treatment outcome. “What we found will allow a doctor to predict whether or not a medication will work in a patient,” Tavis said.

The process could also be used to analyze other RNA viruses, such as HIV. “It’s a pretty easy process,” Tavis said. “The algorithm can be applied fairly quickly,” although whether it yields anything clinically useful remains to be seen, he said. The full report was published in the Journal of Clinical Investigation (Aurora R, Donlin MJ, Cannon NA, Tavis JE. Genome-wide hepatitis C virus amino acid covariance networks can predict response to antiviral therapy in humans. J Clin Invest. 2009;119:225-236. doi:10.1172/JCI37085). [CDC HIV/Hepatitis/STD/TB Prevention News Update, Tuesday, December 23, 2008]

HIV Infects Women Through Intact Healthy Tissue
A new study shows that HIV targets healthy genital tissue in women and not just breaks in the skin, as had previously been thought (Steenhuysen J. Reuters. December 16, 2008). “Normal skin is vulnerable,” said Thomas Hope of Northwestern University’s Feinberg School of Medicine, Chicago, who presented the study’s findings at the December meeting of the American Society for Cell Biology in San Francisco. “It was previously thought there had to be a break in it somehow,” he said.

Using a new technique they devised, Hope and colleagues at Northwestern University and Tulane University, New Orleans, worked with vaginal tissue removed during hysterectomies. They introduced HIV tagged with fluorescent, light-activated tracers, then watched under a microscope as the virus penetrated the outer lining of the female genital tract (the squamous epithelium). They also observed the same process in nonhuman primates.

In both cases, the researchers found that HIV was able to rapidly move past the genital skin barrier to reach immune cells deeper in the tissue. According to Hope, the findings suggest that HIV takes aim at places in the skin that had recently shed skin cells, similar to the way skin on the body flakes off. Scientists previously assumed that HIV required a break in the skin or that it gained access through a single layer of skin cells that line the cervical canal.

The study may help explain the failure of some efforts to prevent HIV infection in women. One clinical trial in Africa in which women used a diaphragm to block the cervix had no effect on reducing HIV transmission, Hope noted. In studies of drugs designed to prevent lesions in genital herpes, the drugs have been ineffective in preventing HIV infection, he said. What the study’s findings make clear is the need for the use of condoms, which are highly effective in blocking HIV transmission. “The sad part is if people just used a condom, we wouldn’t have this problem,” Hope said. [CDC HIV/Hepatitis/STD/TB Prevention News Update, Wednesday, December 17, 2008]

Male Circumcision Lowers Cervical Cancer Risk
Three new studies suggest that male circumcision may help protect men from contracting human papillomavirus (HPV) and HIV (Fox M. Reuters. December 18, 2008). In a study involving more than 1200 men aged 18 to 24 in Orange Farm, South Africa, just 14.8% of those circumcised had HPV infection, compared with 22.3% of men who were uncircumcised. “This finding explains why women with circumcised partners are at a lower risk of cervical cancer and genital warts,” concluded Dr Bertran Auvert of the University of Versailles, France, and colleagues. HPV is the cause of most cases of cervical cancer and genital warts.

A second study of 463 US men had more mixed results, but it did find some indication that male circumcision could protect against HPV infection of the urethra, glans/corona, and penile shaft. Circumcised men were about half as likely to have HPV infection as uncircumcised men, after adjusting for other differences between the groups, according to Carrie Nielson of Oregon Health & Science University, Portland, and colleagues.

In the third report, researchers found that among heterosexual African American men in Baltimore at high risk for HIV infection, 10% of the circumcised men were HIV-infected, compared with 22% of men who were not circumcised. “Circumcision was associated with substantially reduced HIV risk in patients with known HIV exposure, suggesting that results of other studies demonstrating reduced HIV risk for circumcision among heterosexual men likely can be generalized to the US context,” concluded Lee Warner of the CDC and colleagues.

“In the United States, circumcision is less common among African American and Hispanic men, who are also the subgroups most at risk of HIV,” noted an accompanying editorial. “Thus circumcision may afford an additional means of protection from HIV in these at-risk minorities.” However, because the American Academy of Pediatrics does not recommend routine circumcision of newborns, Medicaid does not cover the procedure’s cost. The editorial states that “this is particularly disadvantageous for poorer African American and Hispanic boys who, as adults, may face high HIV risk exposure.”

The results of the studies, as well as an editorial, were published in the Journal of Infectious Diseases (Auvert B, Sobngwi-Tambekou J, Cutler E, et al. Effect of male circumcision on prevalence of high-risk human papillomavirus in young men: results of a randomized controlled trial conducted in Orange Farm, South Africa; Nielson CM, Schiaffino MK, Dunne EF, et al. Associations between male anogenital human papillomavirus infection and circumcision by anatomic site sampled and lifetime number of female sex partners; Warner L, Ghanem KG, Newman DR, et al. Male circumcision and risk of HIV infection among heterosexual African American men attending Baltimore sexually transmitted disease clinics; Gray RH, Wawer MJ, Serwadda D, Kigozi G. The role of male circumcision in the prevention of human papillomavirus and HIV infection. J Infect Dis. 2009;199:14-9, 7-13, 59-65, and 1-3, respectively). [CDC HIV/Hepatitis/STD/TB Prevention News Update, Friday, December 19, 2008]

WHO’s Idea for Universal HIV Testing Raises Hopes and Fears
AIDS experts and public health advocates are weighing in on a recent study that suggested the AIDS epidemic could be reversed by an aggressive test-and-treat strategy (Hoffet N. Inter Press Service. December 10, 2008). “Universal and annual voluntary testing followed by immediate antiretroviral therapy treatment can reduce new HIV cases by 95% within 10 years,” according to the mathematical modeling study by World Health Organization (WHO) researchers, who used data from South Africa and Malawi. The study was published in The Lancet.

Experts greeted the findings with hope but raised several cautionary issues. “We have to look carefully at how people are being tested, by whom, if they are being properly counseled, if it is truly voluntary,” said Patricia Daoust, director of the Physicians for Human Rights’ Health Action AIDS Campaign.

“Concerning annual voluntary testing, it’s difficult to imagine you get 100% testing [while] making sure it is confidential and voluntary,” said Kevin Moody of the Global Network of People Living with HIV/AIDS. “There is still a lot of stigma and discrimination against [HIV-positive] people, so it is important to work with countries to make a safe environment for people to get tested.”

“Currently, the upscale of prevention and treatment programs is undermined by gender inequality, violence against women, against sexual minorities, mandatory testing, lack of confidentiality, stigma and discrimination, and criminalization of sex workers and drug users,” said Mandeep Dhaliwal of the UN Development Program’s HIV/AIDS division.

Seth Berkley, president of the International AIDS Vaccine Initiative, voiced concern about the effects of drug resistance on such a program. “First-line antiretrovirals have become less toxic, but second- and third-line treatments, which would be required when drug resistance occurs, are much more toxic and much more expensive.” Berkley acknowledged that “in theory, this new model would work,” but he added, “given the impracticality of this intervention, it is unlikely to work in a real life situation.” [CDC HIV/Hepatitis/STD/TB Prevention News Update, Friday, December 12, 2008]

FDA Approves New HIV Blood Test From Roche
On December 29, 2008, federal regulators announced they have approved a Roche human plasma test for HIV, including HIV-2 and HIV-1 group O strains (Associated Press. December 30, 2008). The latter strains are mainly found in patients from Africa, but the FDA said cases have recently been detected in the United States. The TaqScreen MPX Test also screens for hepatitis B and C viruses. For more information, visit http://www.fda.gov/cber/approvltr/cobasmpx123008L.htm. [CDC HIV/Hepatitis/STD/TB Prevention News Update, Thursday, January 8, 2009]