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Study Finds Chronic Jet Lag-like Body Clocks in PLWH

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People living with HIV (PLWH) had an “untimed circadian phase” and shorter nocturnal sleep compared to HIV-negative people with a similar lifestyle.

“It is well known that people living with HIV often have trouble sleeping, and many different reasons have been suggested,” co-author Malcolm von Schantz, PhD, professor of chronobiology at Northumbria University in Newcastle upon Tyne, UK, told Medscape . “But what is new about our findings is the observation of delayed circadian rhythms.”

The timed circadian phase in people living with HIV is associated with later falling asleep and earlier awakening, and has “important potential implications” for the health and well-being of people living with HIV, wrote senior author Karine Scheuermaier, MD , from the University of the Witwatersrand in Johannesburg. South Africa and co-authors.

To date, research on sleep in HIV has focused primarily on its homeostatic components, such as sleep duration and staging, and not on circadian aspects, they noted.

“If the lifestyle-independent circadian misalignment observed in the current study is confirmed to be a constant feature of chronic HIV infection, then it may be a mediator of both poorer sleep health and poorer physical health in people living with HIV who may be.” this could be alleviated by light therapy or chronobiotic drugs or dietary supplements,” they suggested.

HIV endemic in the study population

The study analyzed a random sample of 187 participants (36 with HIV and 151 without) in the HAALSI study (Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa), which is part of the Agincourt Health and Socio-demographic Surveillance System .

The study population ranged in age from 45 to 93 years, with a mean age of 60.6 years in the HIV-positive group and 68.2 years in the HIV-negative group. Demographic data, Pittsburgh Sleep Quality Index score and valid actigraphy (measured with an accelerometer for 14 consecutive days) were available for 172 participants (18% with HIV). A subset of 51 participants (22% with HIV) also had valid data on low light onset melatonin (DLMO), a sensitive measure of the circadian clock. DLMO was measured for at least 5 consecutive days with hourly saliva samples between 5:00 p.m. and 11:00 p.m. in a dimly lit room.

In 36 participants (16% with HIV) with both valid actigraphy and DLMO data, the circadian phase angle of carry-over was calculated by subtracting the DLMO time from the habitual sleep onset time obtained by actigraphy.

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After adjusting for age and gender, the study found a slightly later sleep onset (adjusted average delay of 10 minutes), earlier awakening (adjusted average lead time of 10 minutes), and shorter sleep duration in people with HIV compared to HIV-negative participants.

At the same time, people with HIV began producing melatonin more than an hour later, on average, than HIV-negative participants, “with half of the HIV+ group having an earlier habitual sleep onset than the DLMO time,” the authors wrote. In a subgroup of 36 participants, both valid actigraphy and DLMO data, the median circadian phase angle of entrainment was smaller than people with HIV (-6 minutes versus +1 hour 25 minutes in the HIV-negative group).

“Overall, our data suggest that the sleep phase in HIV+ participants occurred earlier than would be biologically optimal,” they added.

Asynchrony between bedtime and circadian time

“Ideally, with this delayed circadian phase timing, they should have delayed their sleep phase (sleep time) by the same amount in order to sleep at their optimal biological time,” Scheuermaier told Medscape Medical News. “Their sleep onset was delayed by 12 minutes (statistically significant, but biologically not that much), while their circadian phase was delayed by more than an hour.”

Possible consequences of a smaller entrainment phase angle include difficulty falling asleep and maintaining sleep, the authors wrote. “The shorter, potentially mistimed sleep observed in this study relative to the endogenous circadian cycle provides objectively measured evidence that supports the numerous previous subjective reports of poor sleep quality and insomnia in people living with HIV.”

They noted that a strength of their study is that the participants were recruited from rural South Africa, where HIV prevalence does not affect the so-called “high-risk” groups of gay men, other men who have sex with men, people People who inject are restricted to drugs and sex workers.

“Behavioral factors associated with belonging to one or more of these groups would be strong potential confounders for sleep and circadian phase studies,” they explained. “In contrast, the epidemic in rural southern Africa was less demographically discriminatory… There are no significant lifestyle differences between the HIV and HIV+ individuals in this study. Members of this aging population are largely past retirement age, living quiet, rural lives supported by government remittances and subsistence farming.”

Direct evidence warrants further study

The study is “unique” in that it provides “the first direct evidence of potential circadian disruption in PWLH,” agreed Peng Li, PhD, who was not affiliated with the study.

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“Evaluating low-light melatonin onset in people living with HIV is a strength of the study; along with the actigraphy-based assessment of onset of sleep, it provides a measure of the phase angle of entrainment,” said Li, research director of the Medical Biodynamics Program, Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, Boston, Massachusetts.

But actigraphy has limitations that affect the interpretation of the results, he told Medscape.

“Without the help of sleep diaries, low specificity in assessing sleep using actigraphy has been consistently reported,” he said. “The low specificity means a significant overestimation of sleep. This lowers the value of the reported sleep indicators and limits the validity of the sleep onset estimate, especially considering that the differences in sleep measurements between the two groups are relatively small, compromising the clinical power.”

He also explained that it’s not clear whether study participants’ sleep onset was spontaneous or “forced” to conform to routines. “This is a limitation in field studies compared to studies in the laboratory,” he said.

Li also noted the small sample size and younger age of people living with HIV, suggesting the study may have benefited from a more concerted design. Finally, he said the study did not examine gender differences.

“It is known in the general population that females are usually in an advanced circadian phase compared to males… More rigorous design and sex/gender-based analyzes are warranted, particularly in this often marginalized population, to assess HIV-specific or general clinical better inform policies. “

The study was supported by the Academy of Medical Sciences. The authors did not mention any conflicts of interest. Li reported grant support from the BrightFocus Foundation. The study is not directly related to this work. He also receives grants from the NIH through a Departmental Award, the Harvard University Center for AIDS Research, and a pilot, HIV and Aging Research Consortium. The projects deal with circadian disorders and cognitive performance in people living with HIV.

J Pineal Res. Oct 29, 2022;e12838. full text

Kate Johnson is a Montreal-based freelance medical journalist who has written on all aspects of medicine for more than 30 years.

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