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Study Finds Biological Clocks Similar to Chronic Jet Lag in PLWH

People living with HIV (PLWH) had a “mistimed circadian phase” and a shorter night’s sleep compared with HIV-negative people with a similar lifestyle, according to the findings that suggest both a possible mechanism for the increased of comorbidities in PLWH as possible solutions.

“It is well known that sleep problems are common in people living with HIV, and many different reasons have been proposed for this,” said co-author Malcolm von Schantz, PhD, a professor of chronobiology at Northumbria University in Newcastle. upon Tyne, UK. he told Medscape. “But the novelty of our findings is the observation of delayed circadian rhythms.”

The untimely circadian phase in PLWH is associated with later sleep onset and earlier awakening and has “important potential implications” for the health and well-being of PLWH, wrote lead author Karine Scheuermaier, MD, of the University of the Witwatersrand, in Johannesburg, South Africa and co-authors.

Until now, research on sleep in HIV has focused primarily on its homeostatic components, such as sleep duration and stage, rather than circadian rhythm-related aspects, they noted.

“If the lifestyle-independent circadian misalignment observed in the current study is confirmed to be a consistent feature of the HIV infectioncould then be a mediator of both poorer sleep health and poorer physical health in PLWH, which could potentially be alleviated by phototherapy or chronobiotic medication or supplementation,” they suggested.

Endemic HIV in the study population

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

The study population ranged from 45 to 93 years of age, with an average 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% HIV-positive). A subgroup of 51 participants (22% with HIV) also had valid dim light melatonin data onset (DLMO), a sensitive measure of the internal circadian clock. DLMO was measured for a minimum of 5 consecutive days with hourly saliva samples between 17:00 and 23:00 while he was sitting in a dimly lit room.

In 36 participants (16% HIV-positive) with valid actigraphy and DLMO data, the circadian phase synchronization angle was calculated by subtracting the DLMO time from the usual sleep onset time obtained from actigraphy.

After adjusting for age and sex, the study found slightly later sleep onset (adjusted average delay 10 minutes), earlier awakening (adjusted average advance 10 minutes), and shorter sleep duration in PLWH in comparison with HIV-negative participants.

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

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

Asynchrony between bedtime and circadian time

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

Possible consequences of a smaller entrainment phase angle include difficulty initiating and maintaining sleep, the authors wrote. “The shorter and potentially untimely sleep relative to the endogenous circadian cycle observed in this study provides objectively measured evidence supporting the abundant previous subjective reports of poor sleep quality and insomnia in PLWH”.

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

“Behavioral factors associated with membership in one or more of these groups would be important potential confounders for studies of sleep and circadian phase,” they explained. “By contrast, in rural southern Africa, the epidemic has been less demographically discriminatory…There are no notable differences in lifestyle between HIV-positive and HIV-positive people in this study. Members of this aging population are mostly 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 possible circadian disturbances in PWLH,” agreed Peng Li, PhD, who was not involved in the study.

“The assessment of dim-light melatonin onset in PLWH is a strength of the study; together with the actigraphy-based assessment of sleep onset, it provides a measure of entrainment phase angle,” said Li, who is director of research program of the Medical Biodynamics Program. , Division of Circadian and Sleep Disorders, Brigham and Women’s Hospital, Boston, Massachusetts.

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

“Without the aid of sleep diaries, low specificity in sleep assessment using actigraphy has been consistently reported,” he said. “Low specificity means a significant overestimation of sleep. This reduces the value of the reported sleep readings and limits the validity of the estimate of sleep onset, especially considering that the differences in sleep measures between the two groups are relatively small.” , thus compromising clinical significance.”

In addition, he explained that it is not clear whether the study participants’ sleep onset was spontaneous or was “forced” to fit into routines. “This is a limitation in the field study compared to laboratory studies,” she said.

Li also pointed to the small sample size and younger age of the PLWH, suggesting that the study could have benefited from a pooled design. Finally, she said the study didn’t look at gender differences.

“In the general population, it is known that women tend to have an advanced circadian phase compared to men…More rigorous sex/gender-based design and analysis is warranted, especially in this often underserved population, to better inform general or HIV-specific clinical guidelines.”

The study was supported by the Academy of Medical Sciences. The authors did not mention any conflict of interest. Li reported on the support of a grant from the BrightFocus Foundation. The study is not directly related to this article. It also receives a grant from the NIH through a Departmental Award, the Harvard University Center for AIDS Research and a Pilot Project, the HIV and Aging Research Consortium. The projects are about circadian disturbances and cognitive performance in PLWH.

Res J Pineal. 2022 Oct 29;e12838. Text complete

kate johnson is a Montreal-based freelance medical journalist who has been writing for over 30 years on all areas of medicine.

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