索馬魯肽(Semaglutide)可減輕與抗反轉錄病毒療法相關的體重和脂肪積累，從而讓愛滋病毒遠離。

Mariana Lenharo / 2024 年 3 月 11 日 / 新聞 / 自然

長期使用抗愛滋病毒藥物會導致愛滋病毒感染者脂肪異常堆積。

圖片來源：何塞·卡爾沃/SPL

愛滋病毒感染者是最新受益於新一代抗肥胖藥物的族群。如果有關治療效果的早期數據得到證實，這些藥物可能成為控制抗愛滋病藥物通常引起愛滋病毒感染者代謝問題的關鍵。

改變遊戲規則的肥胖藥物成為主流：科學家正在學習什麼

加州大學聖地牙哥分校醫學中心的醫生丹尼爾李(Daniel Lee) 表示，愛滋病毒感染者中超重或肥胖的人數正在增加，這引起了受影響個人和醫療服務提供者對索馬魯肽等藥物的興趣。在他的診所治療因愛滋病毒治療而出現代謝併發症的患者，大約 20% 的患者已經接受了索馬魯肽或其他同類藥物的治療。

「在很大程度上，我們在使用這些藥物方面擁有非常好的經驗，」李說。但到目前為止，很少有研究關注重磅抗肥胖藥物對愛滋病毒感染者的影響。

不需要的副作用

儘管愛滋病毒感染者肥胖發生率的增加與一般人群的趨勢相似，但某些用於抑制愛滋病毒的抗反轉錄病毒藥物可能會進一步導致這些人的體重增加和體重相關的疾病。

索馬魯肽(Semaglutide) 的商品名為 Wegovy（治療肥胖症）和 Ozempic（治療糖尿病），模仿一種名為胰高血糖素樣勝肽 1 的激素，有助於降低血糖水平並控制食慾。對於超重或肥胖的人，該藥物可促進體重大幅減輕。

在 3 月 4 日的演講中，愛滋病研究綜合臨床系統網絡（美國各地的愛滋病毒診所）的研究人員描述了他們對 222 名接受愛滋病毒照護的人使用索馬魯肽的分析。該藥物在一年左右的時間平均體重減輕 6.5 公斤，即初始體重的 5.7%。

幫助脂肪肝

抗愛滋病毒療法也與異常脂肪堆積有關。影響 30-40% HIV 感染者的一種疾病是代謝功能障礙相關的脂肪肝病，其特徵是肝臟中脂肪堆積。隨著病情的進展，可能會導致肝衰竭和心血管疾病。「我們確實知道，愛滋病毒感染者患有更嚴重的脂肪肝疾病」，休士頓德州大學健康科學中心的傳染病醫生喬丹·萊克（Jordan Lake）說。但目前還沒有核准的藥物可以治療這種情況。

脂肪肝疾病：扭轉局面

她和她的同事對患有愛滋病毒和代謝功能障礙相關脂肪肝病的患者每週注射索馬魯肽大約六個月的情況進行了評估。 3 月 5 日公佈的結果顯示，29% 的參與者的肝臟疾病完全消失。萊克在會議上說：「我們看到，即使在這麼短的時間內，肝臟脂肪也確實出現了臨床上顯著的減少」。

但同一研究的數據顯示，服用索馬魯肽的參與者肌肉體積減少，在其他服用藥物的人中也觀察到了這種效果。 60 歲或以上的人受影響最大。 Lee 指出，感染愛滋病毒的老年人特別容易遭受與索馬魯肽相關的肌肉損失，醫療保健提供者應密切注意。

抑制發炎

會議上的另一場演講探討了索馬魯肽用於治療愛滋病毒感染者脂肪肥大的情況。查爾斯頓南卡羅來納醫科大學的傳染病兒科醫生艾莉森·埃卡德 (Allison Eckard) 表示，其特點是腹部脂肪堆積，「與發炎增加有關，並增加心臟代謝風險」。「我們目前的治療方法很少，而且這些治療方法通常表現出無效的反應率」。

在早期的臨床試驗中，埃卡德和她的同事掃描了愛滋病毒和脂肪肥大患者的身體，發現索馬魯肽有助於減少腹部脂肪。他們於 10 月在麻薩諸塞州波士頓舉行的傳染病專家和流行病學家會議 IDWeek 上展示了這項研究的結果。並且在會議上在丹佛，研究小組發現，與未服用索馬魯肽的研究參與者相比，服用索馬魯肽的研究參與者中一種名為 C 反應蛋白的發炎血液標記物下降了近 40%。

李說，這可能是重要的影響，因為即使愛滋病毒得到良好控制，也會導致慢性發炎狀態。而且，他說，「如果發炎增加，可能會導致各種終末器官疾病，當然包括心血管疾病，還有肝臟、腎臟、大腦、認知功能等等」。

doi：https://doi.org/10.1038/d41586-024-00691-8

參考文獻：

1. Gómez-Ayerbe, C. 等人。 《國際性病愛滋病期刊 》。33, 1119–1123 (2022)。

2. Bansi-Matharu L.等。 《刺胳針愛滋病毒》。 8，e711–e722 (2021)。

3. Wilding, J. P. H. 等人。 《新英格蘭期刊》。384, 989–1002 (2021)。

Blockbuster obesity drug leads to better health in people with HIV

Semaglutide reduces weight and fat accumulation associated with the antiretroviral regimen that keeps HIV at bay.

Long-term use of antiretroviral drugs can cause abnormal fat accumulation in people with HIV.

Credit: Jose Calvo/SPL

People with HIV are the latest group to benefit from the new generation of anti-obesity drugs. If early data about the treatments’ effects are confirmed, the drugs could become key to controlling the metabolic problems often caused by anti-HIV medications.

Studies presented last week at the Conference on Retroviruses and Opportunistic Infections in Denver, Colorado, suggest that the anti-obesity drug semaglutide not only helps people with HIV to lose weight but also reduces certain conditions associated with fat accumulation that are especially common in people infected with the virus.

Game-changing obesity drugs go mainstream: what scientists are learning

The number of people who are overweight or have obesity is increasing among those with HIV, driving interest among both affected individuals and medical providers in medications such as semaglutide, says Daniel Lee, a physician at the University of California San Diego Medical Center. At his clinic, which treats people with metabolic complications of HIV therapies, around 20% of patients already receive semaglutide or other drugs of the same class.

“For the most part, we’ve had very good experiences with these medications,” Lee says. But, so far, few studies have looked at the effect of the blockbuster anti-obesity drugs on people with HIV.

Unwanted side effects

Although the increasing incidence of obesity in people with HIV is similar to the trend in the general population, certain antiretroviral medications used to suppress HIV could contribute further to weight gain and weight-related conditions in these individuals.

Semaglutide, marketed as Wegovy for obesity and Ozempic for diabetes, mimics a hormone called glucagon-like peptide 1, which helps to lower blood sugar levels and control appetite. In people who are overweight or have obesity, the drug promotes substantial weight loss3.

In a talk on 4 March, researchers at the Centers for AIDS Research Network of Integrated Clinical Systems, a group of HIV clinics across the United States, described their analysis of semaglutide use by 222 individuals receiving HIV care. The drug was associated with an average weight loss of 6.5 kilograms in around one year, or 5.7% of initial body weight.

Helping a fatty liver

Antiretroviral therapies have also been associated with abnormal fat accumulation. One condition affecting 30–40% of people with HIV is metabolic dysfunction-associated steatotic liver disease, which is characterized by the build-up of fat in the liver. As the condition progresses, it can result in liver failure and cardiovascular disease. “We do know that people with HIV have a more aggressive form of fatty liver disease,” says Jordan Lake, an infectious-disease physician at the University of Texas Health Science Center at Houston. But there is currently no approved medication to treat the condition.

Fatty liver disease: turning the tide

She and her colleagues evaluated the use of a weekly injection of semaglutide for around six months in people with both HIV and metabolic dysfunction-associated steatotic liver disease. The results, presented on 5 March, demonstrated that 29% of participants had a complete resolution of the liver disease. “What we saw were really great clinically significant reductions in liver fat even over that short period of time,” Lake said at the conference.

But data from the same study show that participants taking semaglutide lost muscle volume, an effect also observed in other people taking the drug. Individuals who were 60 years of age or older were affected the most. Lee notes that older individuals with HIV are especially vulnerable to semaglutide-linked muscle loss and should be followed closely by health-care providers.

Taming inflammation

Another talk at the conference examined the use of semaglutide for a condition called lipohypertrophy in people with HIV. Characterized by the accumulation of abdominal fat, it “is associated with increased inflammation and carries an increased cardiometabolic risk”, says Allison Eckard, an infectious-disease paediatrician at the Medical University of South Carolina in Charleston. “We have currently few treatments and those treatments often show ineffective response rates.”

Obesity drugs have another superpower: taming inflammation

In an earlier clinical trial, Eckard and her colleagues scanned the bodies of people with HIV and lipohypertrophy and found that semaglutide helped to reduce abdominal fat. They had presented results from that study in October at IDWeek, a meeting of infectious-disease specialists and epidemiologists in Boston, Massachusetts. And at the conference in Denver, the team showed that a blood marker of inflammation called C-reactive protein fell by almost 40% in study participants who took semaglutide compared with those who did not.

That could be an important effect, because even well-controlled HIV leads to a chronic state of inflammation, Lee says. And, he says, “if there’s increased inflammation, it can lead to end-organ disease of all sorts, including certainly cardiovascular outcomes, but also liver, kidney, brain, cognitive function, you name it”.

doi: https://doi.org/10.1038/d41586-024-00691-8

References

1. Gómez-Ayerbe, C. et al. Int. J. STD AIDS 33, 1119–1123 (2022).
2. Bansi-Matharu L. et al. Lancet HIV 8, e711–e722 (2021).
3. Wilding, J. P. H. et al. N. Engl. J. Med. 384, 989–1002 (2021).