Medication adherence often low in children with HIV

Caregivers should not allow children to prematurely assume responsibility for their medication regimen.

Teens and young adults represent 25% of the sexually active po

Increased caregiver knowledge and fewer disagreements about medication responsibility are both associated with better adherence to highly active antiretroviral therapy regimens in children and adolescents with HIV, according to a report in The Pediatric Infectious Disease Journal.

“I encourage health care professionals to ask families about the specific factors that make it difficult to remain adherent,” said Staci Martin, PhD, psychologist at the National Cancer Institute and Medical Illness Counseling Center. “Each family is unique, and understanding the variables that are contributing to poor adherence in a given family will allow clinicians to help the family overcome those obstacles and achieve a higher level of adherence.”

Martin and colleagues from the NIH conducted a longitudinal study involving 13 boys and 11 girls with HIV who were receiving HAART, and their caregivers.

The six-month study enabled the researchers to analyze disease knowledge, baseline responsibility for medication and adherence to HAART regimens among the children and adolescents.

Findings

The researchers included children aged between 8 and 18 years (mean age, 13.9) who had been on HAART therapy that included a protease inhibitor for at least three months, and had vertically-acquired HIV. They did not include patients who received a protease inhibitor through a gastrostomy tube. The number of medications the children received ranged from two to six, but most children received three (n=17) or four medications (n=4).

Most of the children were either black (46%) or white (42%); 54% of the children were living in two-parent homes and 42% were living with a biological parent. Most of the primary caregivers completed high school (92%). One-third had HIV. The researchers obtained the children’s viral loads and CD4 T-lymphocyte counts at baseline, month three and month six.

Children and caregivers completed the Responsibility for Medication Scale (RMS), which asked who held the primary responsibility for medication-related tasks, including who had to take the pills from the container and who was responsible for remembering to take medicine when away from home. The children and caregivers completed the HIV Knowledge Questionnaire so the researchers could measure their general knowledge of the disease and adherence.

The children and caregivers also completed the Pills Identification Test (PIT). The researchers presented a chart to the participants with all antiretroviral therapies pictured and asked them to point to and name all of the current medications the child was currently receiving, how many doses and how many pills were included in each dose. The researchers also analyzed regimen complexity.

They used the Medication Event Monitoring System (MEMS) to track medication adherence in 17 of the participating families. The MEMS used a microelectronic circuit to track exact dates and times the pill bottles were opened.

Adherence rates

The researchers found no differences in adherence rates based on the child’s age, sex or relationship to the caregiver, caregiver HIV status, family composition or caregiver education level. According to the RMS results, the caregivers perceived the children to have less responsibility than the children felt they had.

At least half of the families disagreed on the responsibilities of remembering to bring the medicine when away from home (50%), reporting adverse events (54%), remembering to take the medicine while away (58%) and remembering when to take the medicine (67%). The researchers found a positive association with the child’s age and his caregivers’, and his own perceptions of responsibility.

Caregivers scored significantly higher on the HIV Knowledge Questionnaire compared with the children (P<.05), but the caregivers’ education levels or the child’s age had no effects on scores.

All 24 children and 21 caregivers provided the researchers with PIT results. The caregivers scored higher on dosing schedule knowledge than visual identification (P<.01) and naming (P<.01). The children also scored higher on dosing schedule knowledge than visual identification (P<.01) and naming (P<.001).

Adherence importance

Only four children (17%) maintained an adherence rate of at least 90%, which is the minimum necessary level to achieve adequate viral suppression at three months, and only five children (21%) achieved an adherence level of at least 90% at six months. The mean adherence rate was 80.9% at time one and 78.5% at time two; the decline was not statistically significant, the researchers said.

The researchers found no significant relationships between child and caregiver perceptions of responsibility and disease knowledge. In addition, child and caregiver scores on the HIV Knowledge Questionnaire, PIT or RMS were not associated with antiretroviral regimen complexity.

Better regimen knowledge among caregivers was associated with better outcomes, Martin said. Reducing discrepancies involving responsibility between caregiver and child also improves medication adherence, the researchers said.

Physicians should encourage caregivers to remain involved in medication regimens, even as the child becomes a teenager and resists, according to Martin.

“The most essential thing that physicians and other health care professionals can do to improve adherence is to communicate with families in a nonjudgmental manner about the importance of remaining adherent to a complex medical regimen,” Martin said.

She said that teenagers, particularly, could resist supervision by their caregiver as they become more independent, but caregivers should still have an active part in the teenager’s medication regimen.

“Although it is a teenager’s job to test authority and to ‘mess up,’ for teens with HIV, managing their medical regimen is one area in which they cannot afford to make mistakes. For this reason, it is imperative for caregivers to continue to monitor their child’s adherence, even if they are confident that their child is managing just fine on their own,” Martin said.

The researchers acknowledged several limitations. They replaced two malfunctioning MEMS caps, and several families had unexplained bottle openings, which the researchers had to exclude. They included a small sample size, and some of the families that did not opt for the MEMS arm of the study could have been less adherent than the families who chose to use MEMS.

The researchers recommended further studies aimed at addressing a goal to overcome adherence obstacles. – by Lauren Riley

For more information:

• Martin S, Elliott-DeSorbo DK, Wolters PL, et al. Patient, caregiver and regimen characteristics associated with adherence to highly active antiretroviral therapy among HIV-infected children and adolescents. Pediatr Infect Dis J. 2007;26:61-67.

pulation; however, 15- to 24-year-olds account for nearly half of all sexually transmitted disease diagnoses each year. These STDs can have a variety of health effects.

“Adolescents never think of the consequence of their immediate actions, much less things like infertility 10 years down the line or cancer risk,” said Martin G. Ottolini, MD, at the 19th Annual Infectious Diseases in Children Symposium, held in New York.

Although STDs are treated and diagnosed in individual patients, physicians and pediatricians should think about the general population and the global approach for diagnosis, prevention and treatment, according to Ottolini.

“We have to know a little bit about the epidemiology of STDs, what’s happening in our cities in our nation and in the world. Otherwise we won’t keep up with what to do with individual patients,” said Ottolini, associate professor of pediatrics, microbiology and emerging infectious diseases at the Uniformed Services University of the Health Sciences, and Wilford Hall USAF Medical Center. “This is the sort of thing you don’t necessarily see every day.”

He advised physicians to use the resources available to them to review STD epidemiology, and refer to the CDC for information about STD prevention and treatment recommendations when treating adolescent patients.

STD epidemiology

About 19 million STD cases are reported each year, with an annual cost of $11 to $17 billion in the U.S. population. Between 1990 and 2003, the annual rates of some STDs declined significantly — gonorrhea cases dropped from 276 to 116 per 100,000 and primary and secondary syphilis dropped almost 10-fold, from 20.3 to 2.5 per 100,000. More recently there has been a plateau of progress, particularly with gonorrhea. Studies indicate that syphilis rates among women are steadily declining, yet are rising again among men.

“I think the bottom line is less fear of HIV,” Ottolini said. “We are seeing recurred risk behaviors in higher subpopulations, like men who have sex with men, which puts them at extreme risk.”

Talking to patients, regardless of age, about potential risk behaviors is important. When treating patients diagnosed with an STD, Ottolini recommended keeping in mind some of the common resistance issues, which have been a major treatment challenge over the years.

In the 1970s, penicillin resistance developed and shortly thereafter, tetracycline resistance emerged. In the 1980s, researchers saw widespread erythromycin and the first signs of ciprofloxacin resistance, while about five years ago changes in cefixime sensitivity began to emerge. More recently, decreased sensitivity to ceftriaxone has been reported. Resistant gonococci have been reported in different locales and with different antibiotics. For example, Port Elizabeth, South Africa, experienced a 60% increase in ciprofloxacin resistance rate between 2003 and 2004, while Michigan reported a 2.9% ciprofloxacin resistance rate during the same time frame, according to Ottolini.

“This is scary because quinolones have long been a mainstay in gonorrhea therapy,” he said. “After that I’m not sure where we’re going to go. Unfortunately too, multi-resistance mutations are occurring in these bugs, which are creating a real challenge.”

If a patient has gonococcal infection and has traveled to Europe, Asia, the Middle East, the Pacific, California or Hawaii, or if they are men who have sex with men, it is safer to assume it is quinolone-resistant gonorrhea, according to Ottolini. The best treatment of quinolone-resistant gonorrhea is injectable ceftriaxone (125 mg), according to Ottolini.

Reducing the prevalence of STDs is also a cost-effective initiative. Data indicate that more than $1.1 billion was saved directly from the reductions in syphilis and gonorrhea cases between 1990 and 2003, and $3.9 billion was saved from the reduced lifetime costs of HIV, as these STDs enhance its transmission.

“This is something we tend not to think about too much directly, but one of every 5,000 cases of syphilis and one of every 50,000 cases of gonorrhea leads to successful HIV infection,” he said.

A look at HIV

According to the CDC, about 1,750 infants were born with HIV annually up until about 1996, a number that has decreased dramatically year after year. However, in 2004, the number of people aged 15 to 19 diagnosed with new HIV infection was 1,080, and the number of those aged 20 to 24 with HIV was 3,762.

“New cases among adolescents and young adults are increasing. In addition, infants perinatally infected during the 1980s and 1990s are entering their teen years, which presents significant challenges in providing long-term medications, ensuring compliance, issues associated with chronic disease and the ongoing challenge of education to reduce risk behaviors,” he said. “We’re experiencing generational HIV now.”

Most new pediatric HIV cases occur in 15- to 24-year-olds, and there have been no reductions in the last four years. The CDC and NIH are focusing significant resources on reducing HIV spread through widespread screening and innovative educational and behavioral research directed toward adolescent populations. In addition, there is an explosion of interest in the global scientific community on developing safer and more effective topical microbicides.

Overall, about 6.2 million new HPV infections and 10,000 cases of cervical cancer occur each year. Approximately 30 types of the 100 HPV strains are sexually transmitted. Types 16 and 18 have strong associations with cervical cancer (more than 70%) and types 6 and 11 are responsible for 90% of genital warts, according to Ottolini. About 24% of women between the ages of 16 and 26 have a positive PCR serology to one of the common HPV serotypes, which still under detects the real prevalence of infection.

HPV prevention

Last June, the FDA approved Merck’s Gardasil, the quadravalent 6, 11, 16, 18 vaccine.

Provisional recommendations for HPV vaccination by the Advisory Committee on Immunization Practices consist of administering three doses at 0, 2 and 6 months for girls aged 11 to 12 years, but it can begin to be administered for those as young as 9 years. The vaccine can be administered if the patient is immunosuppressed, already has genital warts, an abnormal cervical screening or is lactating, but the recommendation is to delay the dose if the patient is pregnant. Contraindications include yeast allergy and serious illness.

With the advent of the HPV vaccine, some major challenges have developed: long-term proof of clinical benefit, lack of education in the public about genital warts and the HPV-cancer link, general mistrust of authority and mistrust of vaccines, and social concerns voiced by some that this elective may encourage sexual promiscuity among adolescents.

“In the end STD communication and education will be critical,” Ottolini said.

For more information:

• Ottolini MG. STD update or “When good adolescents go on spring break.” Presented at: 19th Annual Infectious Diseases in Children Symposium. November 18-19, 2006. New York.
• For more information on STD treatment guidelines visit: www.cdc.gov