In a half-hour presentation on HIV and aging at this year's Conference on Retroviruses and Opportunistic Infections (CROI), Amy Justice, M.D., Ph.D., said there's a belief among many medical providers that HIV accelerates aging-related disease by 20 to 30 years, but she disputed that theory.
When comparing people with HIV to uninfected individuals, she said, "The first question you have to ask is who are the 'uninfected' individuals?" She pointed out that a clinical sample of people ("clinical" meaning that they are living with disease or symptoms) differs from a comparison group made up of a community-based (or general) population. The community-based sample, she said, will be lower in risk for almost any disease you look at.
Also, are the groups' measurement of risk done in the same way? In other words, are they equally expected to have a condition detected? In addition, the U.S. general population overall is much older than people living with HIV. Justice said you would have to match HIV-positive people with others their own age (and similar in other characteristics) for a more accurate comparison.
The Veterans Aging Cohort Study (VACS), of which Justice is principle investigator, looked at this issue and found that for five conditions (lung cancer, heart attack, renal failure, fragility fracture, and liver cirrhosis), people with HIV were getting only two of those conditions earlier, but not by much (two years earlier, at 57 years of age, for lung cancer and four years earlier, at 59, for renal failure). "So there is a difference in some cases, but it's nowhere near as dramatic as people have been suggesting," she said.
Overall, she said it's "almost certainly true" that people with HIV are at greater risk of aging-related diseases, to some extent, but that screening for disease sometimes comes with risk. There needs to be a balance, she said, because what's been shown is the appearance of disease biomarkers at an earlier age, not actual disease. She also noted that aging brings medication prescriptions with it, creating a greater burden on people who are already taking multiple HIV drugs.
View the presentation on aging, along with presentations on bone loss, cardiovascular risk, and neurological problems, online at www.retroconference.org; see the Thursday 6 p.m. session, "The Long and Winding Road of HIV Complications."
There have been mixed findings about a relationship between hormonal contraceptives and women's increased risk of HIV infection or disease progression. New data at this year's CROI was reassuring.
An abstract and oral presentation from the study MIRA (Methods for Improving Reproductive Health in Africa) reports on the 288 women (out of nearly 5,000 women in the study) who became HIV-positive. There was no increased risk of acquiring HIV with oral contraceptives, but there was a moderate one with injectable contraceptives (Depo-Provera and Net-En) in women over age 25 who were co-infected with herpes. The researchers said this shows the importance of condoms in addition to contraceptives, as well as the need for contraceptive options for women at [presumably high] risk of HIV.
In a poster abstract from the important Rakai, Uganda study of serodiscordant couples (one partner is HIV-positive and the other isn't), the research team wrote, "We found no significant increased risk of HIV acquisition in women or transmission to men associated with [hormonal contraceptive] use in HIV discordant couples who were not using condoms." They looked at 288 couples in this category in which the man was positive and the woman was not.
In terms of disease progression in women who are already HIV-positive, the Partners in Prevention HSV/HIV Transmission Study Team noted that "hormonal contraceptives are widely used by HIV-positive women, but their effects on HIV disease progression are unclear." In this report on 2,236 women from seven countries in Eastern Europe, Asia, and Africa, the team wrote, "HIV-positive women should be reassured that using hormonal contraception does not have consequences for their HIV disease progression." This included injectable contraceptives.
The study also referred to the recent WHO (World Health Organization) review of published data that concluded no restrictions on hormonal contraceptives need to be put on HIV-positive women.
There was a wealth of new information on pediatric HIV treatment.
The Children with HIV Early Antiretrovirals (CHER) study in South Africa had already demonstrated the benefit of giving infected infants HIV therapy. This time, the study looked at the use of treatment interruptions in 341 children who finished the study to date.
The researchers reported that children who started HIV therapy early in life and then stopped it at one or two years of age did better than those who had their treatment deferred until they met their government's standards for therapy.
The study was conducted to evaluate the potential benefits of interruptions in terms of taking a break from enforced and often difficult adherence with children, as well as saving money in resource-poor countries. While treatment interruptions have been shown to be detrimental to adults, the researchers noted that children can be expected to have different results. The results here were positive.
Children who had treatment interruptions were put back on therapy when their HIV met standards for receiving therapy. The median time to being put on treatment was 20 weeks for the deferred group, 33 weeks for the group receiving an interruption after one year, and 70 weeks for the group receiving an interruption after two years. The research team wrote, "In HIV-positive infants, early limited ART until first or second birthday followed by interruption appears safe, with better outcomes and less ART exposure than deferred ART." Presenter Dr. Mark Cotton said the interruptions led to better results for all markers of health examined, including survival. The average follow-up was four years, with six years being the longest, he said. He called infants a very vulnerable group that experiences rapid progression of disease.
In a report from Kenya, however, 80% of children who had treatment interruptions (14 children) had to restart therapy three months later. That research group contrasted their findings with the European PENTA study in which more than 50% of children completed a 48-week treatment interruption with few adverse events.
Study P1060 looked at how children's therapy was affected by whether or not they had been exposed to Viramune (nevirapine) around the time of birth for the prevention of mother-to-infant HIV transmission. The infants from six months of age and children to three years of age were given either a Viramune- or a Kaletra-based regimen
Presenter Jane Lindsey, Sc D, said the team found that there was better virus suppression with Kaletra for the children who had been exposed to nevirapine (as could be expected), but that "surprisingly," it also led to greater suppression for the children not exposed to nevirapine. Children on nevirapine, however, experienced better neurologic and height/weight gain. In the study, 164 of the infants and children had been exposed to nevirapine and 288 hadn't.
According to the study abstract conclusion, "These inconsistencies and practical difficulties of using LPV/r [Kaletra] complicate selection of the best ART regimen for infants in resource-poor settings." Lindsey said the results produced "decision-making angst" for providers, since Kaletra is more expensive and the formulation used in the study needs to be kept cold (a greater problem in resource-poor areas).
According to an abstract from another study, PREDICT, "It is uncertain whether nadir [lowest point] CD4 percentage affects neurodevelopmental outcomes." The study of HIV-positive children from Cambodia and Thailand looked at this issue in a sub-study. They reported that at 144 weeks, the children put on immediate therapy did not differ in neurodevelopmental outcomes compared to the children whose therapy was delayed, despite the fact that these children had a lower nadir CD4 percentage and less time on treatment. On a couple of other measures, however, the children on therapy did better: intelligence and Beery scores (a measure of visual-motor problems that can lead to learning, behavior, and neuropsychological problems). In its conclusion, the abstract noted that the findings suggest that "despite effective ART [antiretroviral therapy], children with HIV experience global cognitive challenges" compared to HIV-negative children. At 144 weeks, 69 (48%) of the children had restarted treatment.
Finally, HIV-positive children in a Uganda study had a 41% decreased risk of malaria when using Kaletra compared to using nevirapine. The study of 176 children (87 on Kaletra) is important because of the deadliness of malaria in sub-Saharan Africa.
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