Study finds chronic Jet Lag-like body clocks in PLWH

People living with HIV (PLWH) had “mistimed circadian phases” and shorter nighttime sleep compared to HIV-negative individuals with similar lifestyles, according to findings that suggest both a potential mechanism for increased comorbidity in PLWH and potential solutions.

“It is very well known that sleep problems are common in people living with HIV, and many different reasons have been proposed,” co-author Malcolm von Schantz, PhD, professor of temporal biology at Northumbria University in Newcastle upon Tyne, UK. , Medscape reported. “But what’s new in our results is the observation of a delayed circadian rhythm.”

Irregular circadian phase in PLWH is associated with later sleep and earlier wakefulness and has “significant potential implications” for the health and well-being of PLWH, wrote senior 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 aspects, such as sleep duration and stage, rather than circadian aspects, they said.

“If the lifestyle-independent circadian rhythm observed in this study is confirmed to be a consistent feature of chronic HIV infection, it could be a mediator of both poorer sleep health and poorer physical health in PLWH, which could potentially be ameliorated by phototherapy or chronobiotic drugs or supplements,” suggested they to

HIV endemic in the research group

The study analyzed a random sample of 187 participants (36 with HIV and 151 without) in the HAALSI (Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa) study, 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 scores, and valid activity (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 dim light melatonin (DLMO), a sensitive measure of the internal circadian clock. DLMO was measured for at least 5 consecutive days by saliva sampling every hour between 17:00 and 23:00 while sitting in a dimly lit room.

In the 36 participants (16% with HIV) with both valid CT and DLMO data, the circadian phase angle was calculated by subtracting the DLMO time from the normal sleep onset time obtained from infection.

After adjusting for age and gender, the study found slightly later sleep onset (adjusted mean latency of 10 minutes), earlier awakening (adjusted mean advance of 10 minutes), and shorter sleep duration in PLWH compared to HIV-negative participants.

Meanwhile, melatonin production in PLWH started more than an hour later than in HIV-negative participants, “with half of the HIV+ group having an earlier normal sleep than DLMO time,” the authors wrote. In the subgroup of 36 participants with both valid genotype and DLMO data, the median circadian phase angle of coactivity was lower in 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 rhythm

“Ideally, with this delayed circadian phase timing, they should have delayed their sleep phase (sleep time) by the same amount to sleep at their optimal biological time,” Scheuermaier explained to Medscape. “Their sleep 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 reduced phase angle of restraint include difficulty initiating and maintaining sleep, the authors wrote. “The shorter, possibly mistimed sleep relative to the endogenous circadian cycle observed in this study provides objectively measured evidence that supports many previous subjective reports of poor sleep quality and insomnia in PLWH.”

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

“Behavioral factors associated with belonging to one or more of these groups would be a strong potential confounder for studies of sleep and circadian phase,” they explained. “In contrast, in rural South Africa, the epidemic has been less demographically diverse… There are no appreciable differences in lifestyle between HIV- and HIV+ individuals in this study. Members of this aging population are mostly past retirement age, live in quiet, rural life supported by government money and subsistence farming.”

Direct evidence warrants further investigation

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

“Dim light assessment of melatonin in PLWH is a strength of the study; combined with an entrainment-based assessment of initial sleep, it provides a measure of the phase angle associated with entrainment,” said Li, who is research director of the Medical Biodynamics Program, Division of Sleep and Circadian Diseases, Brigham and Women’s Hospital, Boston, Massachusetts.

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

“Without the aid of a sleep diary, low specificity has been consistently reported in the assessment of sleep using functional assays,” he said. “Low specificity means a significant overestimation of sleep. This lowers the value of the reported sleep readings and limits the validity of the assessment of sleep onset, especially when considering that the difference in sleep measurements between the two groups is relatively small, which comes down to clinical meaning.”

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

Li also noted the small sample size and younger age of PLWH, suggesting that the study may have benefited from a matched design. Finally, he said the study did not examine gender differences.

“In the general population, women are known to typically have an advanced circadian phase compared to men… More rigorous designs and sex/gender-based analyses, particularly in this often marginalized population, are warranted to better inform HIV-specific or general clinical guidelines.” “

The study was supported by the Academy of Medicine. The authors declared no competing interests. Li reported grant support from the BrightFocus Foundation. The research is not directly related to this article. He also receives funding from the NIH through a faculty award, the Harvard University Center for AIDS Research, and a pilot program, the HIV and Aging Research Consortium. The projects are about circadian rhythm disturbances and cognitive performance in PLWH.

J Pineal Res. 2022 Oct 29;e12838. Full text

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

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