This Week in HIV Research: Revisiting Our Needs
When our understanding of a chronic condition evolves over time as much as it has with HIV, there’s an implicit imperative for us to periodically revisit many of our assumptions when it comes to various aspects of patient care. That holds not just for a lot of the most basic aspects of HIV care—e.g., what regimen to prescribe, or how often CD4 and viral load tests are necessary—but also for adjacent health issues and comorbidities, such as cancers related to human papillomavirus (HPV), hepatitis B coinfection, or cardiovascular risk management.
In our latest tour of recently published, peer-reviewed HIV research, we take a peek at new science that highlights areas where it’d be wise for us to re-examine what we think we know, and in turn what we need to do about it. Specifically:
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HPV-related cancer risk is greatly enhanced among women living with HIV (WLWH), necessitating a more aggressive screening approach.
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There’s so much we still need to learn about the interplay between HIV, hepatitis B, and fatty liver disease.
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We need to settle on more accurate tools for measuring the relevance of statin use for people living with HIV.
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We’re still unraveling the relationship between integrase inhibitors and weight gain—and it looks like hormone levels may play an important role.
One thing we definitely need to do is read more about each of these findings. To beat HIV, you have to follow the science!
Improved Cervical Cancer Screening Is Needed for Women With HIV
Even in a single-payer health care system, women living with HIV are at higher risk of developing HPV-associated female genital tract cancers than HIV-negative women, a study published in Clinical Infectious Diseases showed.
Data were analyzed on 1,454 WLWH and 5,816 matched HIV-negative controls who used the US health care system for military veterans between 1999 and 2016. The total number of HPV-associated cancers was relatively small: 28 among WLWH, 32 among controls. However, WLWH were over six times more likely to develop cervical cancer than controls.
The incidence rate ratio for any HPV-related female genital tract cancer was 5.86 for WLWH compared to HIV-negative participants. Anal/rectal cancer, which is often overlooked in women, was also more common in those living with HIV: age- and race-adjusted incidence rates were 12.6 in WLWH compared to 8.35 in HIV-negative women.
The findings stand in relief against an earlier study in the general population, which had shown no difference in incidence by HIV status—provided that women were regularly screened. Despite the fact that this study occurred within a single-payer health care system (i.e., the U.S. Department of Veterans Affairs), participants may not attend safety-net health systems in the first place or may not be adequately followed up, or oncologists may not be comfortable treating WLWH, study authors explained.
Study authors urged improved cervical cancer screenings and follow-up for WLWH in the Veterans Administration health care system.
Further Research Needed into HIV/HBV Coinfection and Fatty Liver Disease
Non-alcoholic fatty liver disease (FLD) is common among people coinfected with HIV and HBV, even if both viruses are under control, a study published in Clinical Infectious Diseases found.
Researchers performed liver biopsies on 114 HIV/HBV coinfected people, 93% of whom were male and 51% of whom were Black. HIV was controlled in 93% of participants (HIV RNA < 400 copies/mL) and HBV in 83% (HBV DNA < 1000 IU/mL). Thirty percent showed fatty liver disease (20% of participants steatosis, 10% steatohepatitis), but there were wide variations by race: FLD was present among 46% of white participants, compared to 16% of Black participants.
Risk factors among PLWH were similar to those among HIV-negative people. Traditional lipid values were no different between participants with and without fatty liver, but atherogenic lipid subfractions were higher in the FLD group. Subfraction trends also correlated with increased triglycerides, suggesting that triglyceride trends could be used as a proxy for atherogenic lipids, which serve as an indicator of cardiovascular risk.
Persistently elevated alanine aminotransferase values were also associated with FLD, even with HBV under control, suggesting that if such values are discovered in a patient, they may warrant evaluation for fatty liver disease, study authors recommended. They noted that they plan to assess the follow-up histology among participants.
A related commentary by Tinsay A. Woreta, M.D., M.P.H., of the Johns Hopkins School of Medicine, and Naga Chalasani, M.D., of the Indiana University School of Medicine, noted that much still needs to be learned about the interplay between HBV, HIV, and liver disease in the wake of this study—including an answer to the question of why FLD was less prevalent among Black participants. They called for additional research, including longitudinal studies with paired liver biopsies.
Coronary Artery Calcium Scoring May More Precisely Identify the Need for Statins
Using coronary artery calcium scoring together with more traditional cardiovascular risk assessment tools could add precision to the process of identifying people living with HIV (PLWH) who need statins, researchers reported in Journal of Acquired Immune Deficiency Syndromes.
The authors scored coronary artery calcium in 739 participants over 50 years old and compared their results to those obtained using the Framingham risk score. No calcification was detected in 23% of participants who had a Framingham risk score of 10% or higher. Conversely, 20% of those in whom calcification was detected had been classified as low risk (i.e., less than 10%) by the Framingham method.
Overall, coronary artery calcium scoring reclassified 43% of participants; 20% were shifted into a higher risk group, suggesting benefits from statin therapy; 24% were shifted into a lower risk group, suggesting previously indicated benefits from statin therapy were in fact not present. Using other traditional tools, such as D:A:D and QRISK2, yielded similar results.
Conventional tools rely heavily on age as input, but this may miss younger PLWH’s CVD risk and overprescribe statins in older PLWH, the study authors noted.
More precise targeting of cholesterol-lowering drugs could improve resource allocation, avoid potential drug-drug interactions with some antiretrovirals, and avoid statin side effects, the authors stated. They called for cost-effectiveness studies in PLWH to confirm their results.
No Weight Gain Seen After Switching to INSTI in Premenopausal Women
Ovarian activity appeared to affect the degree of weight gain experienced after switching to raltegravir (Isentress, an INSTI) and etravirine (Intelence, an NNRTI) in a small study published in AIDS.
The findings derive from a substudy of the French ETRAL trial, in which study participants switched from a protease inhibitor-based antiretroviral regimen to a regimen of etravirine plus raltegravir. The substudy included 165 PLWH with suppressed viral loads, 48 of whom were women. Twelve of the women had not yet reached menopause, six were perimenopausal, and 22 postmenopausal.
At 48 weeks after switching treatment, the body mass index in 75% of premenopausal women remained stable or decreased, while it increased in 71% of peri-/postmenopausal women. By week 96, BMI had increased by 3% on average in men, by 6% in perimenopausal women and by 2% in postmenopausal women, while dropping by 1% in premenopausal women.
“This suggests that functional ovarian activity could protect against raltegravir/etravirine-induced weight gain,” study authors concluded.
Limitations included relatively few women and a lack of data on changes in exercise habits or diet. The study also did not involve dolutegravir (Tivicay), which to date has been the primary INSTI associated with weight increases. As has been well documented, other studies have shown INSTI-induced weight gain in women; the current study’s authors called for additional research to explore this discrepancy in findings.