Older People Face Greater HIV Infection Risks, Incentives Increase Adherence to Treatment for HIV-Infected Methadone Patients, HIV Preexposure Prophylaxis Shows Promise

April 28, 2009

Physicians are failing to diagnose HIV infection among older patients,

Older People Face Greater HIV Infection Risks
Physicians are failing to diagnose HIV infection among older patients, even as many persons over age 50 enjoy extended sex lives thanks to erectile dysfunction drugs, the World Health Organization (WHO) reported in March (MacInnis L. Reuters. March 3, 2009). Sexually active persons age 50 and older are less likely to have protected sex than are younger persons.

“HIV prevalence and incidence in the over-50-year-olds seem surprisingly high, and the risk factors are totally unexplored,” the WHO report’s authors said. “These individuals have a shorter time from diagnosis to the onset of AIDS, reflecting both age-related faster progression to AIDS and doctors’ failure to consider HIV as a diagnosis.”

Sex is the most likely transmission mode among older patients partly because of their uptake of impotence drugs, the WHO said. Older women appear to have a higher risk of infection during condomless sex because of the age-related thinning of the vagina’s lubricating mucous membrane. “Since 1998, erectile dysfunction drugs have been extending the sex life of many older individuals and, at the same time, may be extending the HIV epidemic into older age-groups,” the authors said. “While erectile dysfunction is common and erectile dysfunction drugs are widely available in developing countries, no study has been done of their possible impact on the HIV epidemic, although their use in industrialized countries has been associated with risky safety practices.”

HIV-infected persons older than 50 years account for about 8% of new HIV diagnoses in Europe and 11% in the United States. Risk factors among older patients in developing countries have not been studied nor are prevalence data available, but the WHO report stated that similar infection trends are likely occurring there.

The report was published in the Bulletin of the World Health Organization (Schmid GP, Williams BG, Garcia-Calleja JM, et al. The unexplored story of HIV and ageing. Bull WHO. 2009;87:161-244). [CDC HIV/Hepatitis/STD/TB Prevention News Update, Wednesday, March 4, 2009]

Incentives Increase Adherence to Treatment for HIV-Infected Methadone Patients
The potential benefits of antiretroviral therapy for HIV-infected patients are “not fully realized because of difficulties in adherence with demanding treatment regimens, especially among injection drug users,” according to the authors of a recently published study of methadone patients with HIV infection.

In the study, HIV-positive methadone patients who were less than 80% adherent to their primary antiretroviral therapy were randomized to a trial of incentives for on-time adherence. Vouchers redeemable for goods were issued on an escalating scale to reward adherence. Both intervention and control groups visited a medication coach twice a month. Micro-costing was employed to determine the cost of the intervention. Administrative data and patients' reports of out-of-system care were accessed to obtain other cost information.

During the 12-week intervention, the incremental direct cost of the intervention, including treatment vouchers, was $942. Adherence, as measured by on-time openings of an electronically monitored medication vial, was 78% in the intervention group and 56% in the control group. The voucher group incurred $2572 in antiretroviral drug costs, compared with $1973 for the control group.

“The incremental direct cost of voucher incentives was $292 per month,” the authors concluded. “If the observed increase in adherence from voucher incentives can be sustained in the long term, the literature suggests that disease progression will be slowed. Further research is needed to evaluate if the improvement can be sustained or achieved at lower cost. Mitigation of treatment resistance and reduction in HIV transmission are additional benefits that favor adoption.” The study results were published in Drug and Alcohol Dependence (Barnett PG, Sorenson JL, Wong W, et al. Effect of incentives for medication adherence on health care use and costs in methadone patients with HIV. Drug Alcohol Depend. 2009;100[1-2]:115-121). [CDC HIV/Hepatitis/STD/TB Prevention News Update, Wednesday, February 11, 2009]

HIV Preexposure Prophylaxis Shows Promise
In a study to forecast the clinical, epidemiological, and economic outcomes of HIV preexposure prophylaxis (PrEP) that took into account uncertainties regarding efficacy, the risks of developing drug resistance and toxicity, behavioral disinhibition, and drug costs, the authors reported that “the combination of tenofovir and emtricitabine shows promise as HIV prophylaxis.”

To model PrEP among US men who have sex with men, the researchers adapted a computer simulation of HIV acquisition, detection, and care. Base-case assumptions included 50% efficacy of PrEP and monthly tenofovir/emtricitabine costs of $753. Sensitivity analyses were employed to examine stability of results and to identify critical input parameters.

In a cohort of persons with a mean age of 34 years, the results showed that PrEP reduced lifetime HIV infection risk from 44% to 25% and increased mean life expectancy from 39.9 to 40.7 years (21.7 to 22.2 discounted quality-adjusted life-years). “Discounted mean lifetime treatment costs increased from $81,100 to $232,700 per person, indicating an incremental cost-effectiveness ratio of $298,000 per quality-adjusted life-year gained,” the authors wrote.

When greater (90%) PrEP efficacy was assumed, markedly larger reductions in lifetime infection risk (from 44% to 6%) were noted. Targeting younger populations for whom the incidence of infection is higher and improving the cost and efficacy of PrEP yielded more favorable incremental cost-effectiveness ratios. “PrEP could substantially reduce the incidence of HIV transmission in populations at high risk for HIV infection in the United States,” the authors concluded. “Although it is unlikely to confer sufficient benefits to justify the current costs of tenofovir/emtricitabine, price reductions and/or increases in efficacy could make PrEP a cost-effective option in younger populations or populations at a higher risk for infection. Given recent disappointments in HIV infection prevention and vaccine development, additional study of PrEP-based HIV prevention is warranted.”

The study results were published in Clinical Infectious Diseases (Paltiel AD, Freedberg KA, Scott CA, et al. HIV Pre-exposure prophylaxis in the United States: impact on lifetime infection risk, clinical outcomes and cost-effectiveness. Clin Infect Dis. 2009;48:806-815). [CDC HIV/Hepatitis/STD/TB Prevention News Update, Thursday, February 26, 2009]

Old Drugs Might Give TB a 1-2 Punch
A fresh approach to tuberculosis (TB) treatment using 2 old, safe antibiotics could fight even the deadliest strains of Mycobacterium tuberculosis-extensively drug-resistant M tuberculosis (XDR-TB)- new report suggests (Neergaard L. Associated Press. February 26, 2009).

M tuberculosis organisms contain an enzyme, β-lactamase, that disables the penicillin class of antibiotics. “It chews them up and spits them out and they never get to see their target,” said John Blanchard of the Albert Einstein School of Medicine. However, other antibiotics can block β-lactamase, and Blanchard's team tried using this enzyme-blocking property to flank M tuberculosis, hoping to open it up to a wider spectrum of antibiotic susceptibility. Researchers specifically tapped the antibiotic clavulanate, part of the 2-drug Augmentin antibiotic widely used for various children’s infections, to inhibit the M tuberculosis enzyme.

In the laboratory, clavulanate opened M tuberculosis up to meropenem, an antibiotic in the same class as penicillin, and the combination blocked the growth of 13 different XDR-TB strains. Trials may soon answer whether the combination will work in humans. US researchers from the NIH and New York’s Montefiore Medical Center are planning small patient studies in South Korea and South Africa, which they hope to begin later this year.

“It's very clever,” said Dr Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. The 1-2 treatment punch “leaves the original drug with the capability of doing what it's supposed to do.”

The full report was published in Science (Hugonnet JE, Tremblay LW, Boshoff HI, et al. Meropenem-clavulanate is effective against extensively drug-resistant Mycobacterium tuberculosis. Science. 2009;323:1215-1218). [CDC HIV/Hepatitis/STD/TB Prevention News Update, Tuesday, March 3, 2009]

Treating HIV Infection Immediately Might Stall Immune Decay
Study results presented February 9 at the 16th Conference on Retroviruses and Opportunistic Infections in Montreal found significant benefits may be associated with treating patients immediately following onset of HIV infection (Lauerman J. Bloomberg News. February 9, 2009).

In August, the International AIDS Society recommended that HIV-infected patients start antiretroviral treatment when the CD4+ cell count drops below 350/µL, which can take months or years after onset of infection and varies among patients. But some recent studies have suggested that antiretroviral treatment should be started earlier. A study last year found that HIV-infected persons live longer if treatment is started when CD4+ cell counts fall below 500/µL.

In the new study, Radjin Steingrover of Amsterdam’s Academic Medical Center and colleagues divided patients into 2 groups: 55 patients received 6 to 15 months of treatment, beginning in the early stages of HIV infection. This group progressed to needing long-term treatment in an average of 45 months. Another group of 47 patients who did not receive early treatment progressed to the point of needing long-term treatment after 32 months, the investigators reported. “Until now, the benefits [of early treatment] to the patient have just been theoretical,” said Peter Leone, a University of North Carolina AIDS expert and medical director of the North Carolina Department of Health's HIV branch, who was not involved in the research. “Now we’ve got some idea that there’s benefit to the individual.”

A second study presented at the conference showed that HIV-infected patients live longer when treated before CD4+ cell counts drop below 500/μL, rather than waiting until they reach lower levels. Mari Kitahata of the University of Washington, Seattle, and colleagues found the risk of death from any cause was 60% higher in patients who waited to get antiretroviral treatment.

A third study, led by Jonathan Sterne of the research group When to Start Consortium, looked at patients treated along a spectrum of CD4 levels. The results found that HIV-infected patients lived longer or their disease took more time to progress to AIDS when they were treated earlier.

The challenge, said Leone, is finding newly infected patients. Most HIV infections are diagnosed by the presence of antibodies responding to the virus, proteins that do not appear until a few weeks after infection takes place. North Carolina is the only state that routinely uses a testing method that looks for HIV’s genetic material, which takes only a few days, he said. The studies show that “with our crude tools we may be able to slow the progress of the disease. It suggests that there’s an opportunity to do more, if we have more research on what’s going on in this early period of infection,” said Leone. [CDC HIV/Hepatitis/STD/TB Prevention News Update, Tuesday, February 17, 2009]

Interruptions in HIV Therapy Common in Ex-Inmates
Many HIV-positive inmates receiving drug therapy in prison failed to adhere to treatment on their release, according to new research (Reuters Health. February 24, 2009). The study involved 2115 HIV-positive inmates who were receiving antiretroviral therapy before being released from the Texas prison system between January 2004 and December 2007. Among them, only 5.4% filled their antiretroviral prescription within 10 days, 17.7% within 30 days, and 30% within 60 days. Hispanic and African American former inmates were 60% less likely to fill their prescription within 10 days, and they were 30% less likely to do so within 30 days. Overall, 90% or more of the former inmates did not fill their prescription soon enough to avoid treatment interruption.

“These remarkably high rates of lengthy HIV treatment interruptions are troublesome from a public health perspective,” said lead author Jacques Baillargeon, PhD, of the University of Texas Medical Branch at Galveston. “Several studies suggest that many released inmates who discontinue antiretroviral therapy also resume high-risk behaviors, such as injection drug use or unsafe sex, and this combination may result not only in poor clinical outcomes for these individuals but also in the creation of drug-resistant HIV reservoirs in the general community.”

“Adequately addressing a public health crisis of this scale and complexity will require carefully coordinated efforts between academic institutions, the criminal justice system, and public health agencies,” the authors wrote.

The report was published in the Journal of the American Medical Association (Baillargeon J, Giordano TP, Rich JD, et al. Accessing antiretroviral therapy following release from prison. JAMA. 2009;301:848-857).

Merck Aims for Male Gardasil
Merck & Co’s recent application for US approval of the Gardasil vaccine to prevent human papillomavirus (HPV) in males aged 9 to 26 years likely faces several hurdles in the market if it is approved, say experts. The $360 cost of the 3-shot series would have to be weighed against its benefit for males, for whom HPV can cause genital warts and penile and other rare cancers (Loftus P. Wall Street Journal. February 4, 2009).

A Merck-funded study of 4000 males aged 16 to 26 years who had 5 or fewer lifetime partners at vaccination found Gardasil reduced external genital lesions caused by targeted HPV strains by about 90% at a 29-month follow-up. No penile or other HPV-related cancers were found, but such cancers can take years to develop. Researchers are still investigating whether the vaccine prevented precancerous anal lesions among the study’s subgroup of men who have sex with men, said Rick Haupt, who leads the Merck research unit’s clinical program for HPV vaccines.

Merck has not investigated Gardasil’s efficacy in preventing HPV-related head and neck cancers.

A “herd immunity” rationale for vaccinating males, to reduce their chances of transmitting HPV to partners, could be a tough sell, said experts. It may be too abstract to motivate patients and parents.

The least serious consequence of HPV infection-genital warts-could be the most tangible, motivating factor for patients, said Amanda Dempsey, professor of pediatrics and communicable diseases at the University of Michigan, Ann Arbor. Insurance coverage for the shot would determine whether the vaccine is ever commercially viable for males as well. If the CDC’s vaccine advisory panel recommended the shot for boys and young men, insurers would probably cover it. [CDC HIV/Hepatitis/STD/TB Prevention News Update, Wednesday, February 11, 2009]