Tammy Worth / 2025年6月16日 / Knowable雜誌

63 歲的洛杉磯教師米格爾最近剛迎來了自己被診斷出感染愛滋病毒 38 週年。醫生曾告訴他幾年後他就會死。他時時刻刻擔心，每一次的渡過都可能是最後一次。

米格爾開始服用 AZT（疊氮胸苷），這是第一種用於治療愛滋病毒和愛滋病的抗反轉錄病毒藥物，隨後又陸續服用其他藥物。當他服用一種名為 Crixivan 的藥物時，他的臉頰凹陷，下巴脂肪增加，這是早期 HIV 藥物的特徵。他擺脫了其他早期影響：嚴重頭痛、肌肉疼痛、失眠、貧血和其他血液疾病。 「男同性戀者認為這對身體非常有害」，米格爾（出於隱私原因，他沒有透露他的真名）說道。「但這是一場賭博；如果你接受這個可怕的事情，至少你還有一線生機」。

這些藥物挽救了數百萬人的生命，但一些醫生對早期藥物的長期影響感到疑惑。他們發現了脂質失調和嚴重的神經病變：四肢麻木、刺痛和疼痛。有些人預測，未來男同性戀者和其他愛滋病毒感染者將面臨早期心臟病和心臟病發作的風險。

如今人們已經知道，接受抗病毒治療的愛滋病毒感染者罹患某些慢性疾病的機率確實更高。但研究人員仍不完全確定是什麼原因造成的。研究顯示，一些愛滋病毒藥物，特別是早期藥物，會增加一定的風險，但病毒在體內的低水平持續性存在也會增加風險。找出病因對於監測和治療這群患者非常重要，他們現在有望擁有接近正常的壽命。

美國食品藥物管理局批准了 50 多種可阻止愛滋病毒複製和傳播的抗反轉錄病毒藥物。它們通常作為結合兩種或三種不同類別藥物的一種療法來服用。

服用第一種獲得批准的藥物 AZT 的人經常會發現自己出現消瘦症狀，即非自願性的體重減輕 10% 或更多。相較之下，當今的一些藥物似乎會導致體重增加，科羅拉多大學醫院傳染病專家克里斯汀·埃蘭森說。在《臨床傳染病》雜誌發表的一份針對 2624 名 HIV 陽性患者的 2024 年報告中，她發現抗反轉錄病毒治療第一年的平均體重增加了近 8 磅。

在約 9 年的追蹤期間，約有 5% 的參與者被診斷患有糖尿病，14% 的參與者被診斷出患有代謝症候群（包括肥胖、低水平的「好的」或 高密度膽固醇『HDL膽固醇』和高血糖等的一組疾病），16 名參與者患有中風。雖然有些人聲稱服用新型愛滋病藥物後體重增加，但「許多服用這些藥物的人體重完全正常」，埃蘭德森說。「我們不知道誰會獲益，也不知道為什麼」。

更普遍地說，研究人員將愛滋病毒陽性人群與一系列通常與年齡增長相關的疾病聯繫起來：心血管疾病、認知障礙、糖尿病和虛弱。 「在疫情爆發初期，人們就開始大聲疾呼，愛滋病毒感染者會過早衰老」，阿姆斯特丹大學醫學中心前內科醫生和傳染病專家彼得·賴斯說。「但確實沒有數據支持這一說法」。

為了找到答案，Reiss 和同事在 2010 年開始了一項名為 AGEhIV 的研究，對阿姆斯特丹的 1146 人進行了約 6 年的追蹤調查。超過一半的人是愛滋病毒陽性，其餘的人也是未感染愛滋病毒的類似族群。

科學家發現，愛滋病毒感染者確實更容易罹患高血壓、心臟病、骨質疏鬆症、腎臟疾病和周邊動脈疾病（腿部和腹部動脈變窄，血流減慢）。賴斯說，幾乎所有 HIV 陽性參與者都在服用 HIV 藥物，病毒水平幾乎檢測不到，「所以你實際上談論的是在有效治療 HIV 時發生的情況」。

Reiss 及其同事也發現了與傳統上與 HIV 感染無關的癌症之間的聯繫，例如胃癌、肺癌和血癌。在研究期間死亡的 38 人中，有 16 人死於此類癌症，除一人外，其餘均為 HIV 陽性組。

多年來，已經進行了許多其他人口研究，其結果總體一致：愛滋病毒感染者患各種慢性疾病的風險似乎更高，而且平均預期壽命比愛滋病毒陰性者短 5-10 年。

例如，2022 年對 47 份抗反轉錄病毒療法報告的審查顯示，感染愛滋病毒會使心血管疾病的風險增加一倍，並增加骨骼和肌肉疾病的風險，例如肌肉減少症（肌肉質量和力量逐漸喪失）、憂鬱症和癌症。 2020 年發表的一項美國大型研究發現，2016 年，未感染愛滋病毒的人的平均壽命比感染愛滋病毒的人多 9 年。與愛滋病毒感染者相比，他們平均有 16 年以上沒有其他健康問題。

好消息是，預期壽命差距已大幅縮小，與 21 世紀初的 22 年差距相比，科學家認為這主要是因為現代抗反轉錄病毒藥物和早期開始治療。

是什麼導致了這些差異？美國國家過敏和傳染病研究所前所長安東尼·福奇及其同事在 2019 年《美國醫學會雜誌》的一篇評論文章中指出，了解這一點很重要，因為這些不成比例的慢性病發病率會危害人們的生活，而且代價高昂。他們寫道，治療患有愛滋病毒和心血管疾病或慢性腎臟病的患者每月的費用比單純治療愛滋病毒的患者每月要多 1400 至 5000 美元。

生活方式是其中一個影響因素。賴斯說，愛滋病毒感染者吸菸、飲酒、憂鬱和焦慮的比例更高。但他補充道，這並不能解釋所有與年齡相關的疾病早發現象的增加。

同時，藥物之間的關聯不斷出現。加州大學洛杉磯分校健康中心心臟病學主任 Priscilla Hsue 表示，阿巴卡韋 (Abacavir) 最近被發現與心血管疾病有關。在 2024 年愛滋病大會上，研究人員報告稱，服用過該藥物的人患心臟病和中風等重大心血管疾病的風險比接受其他抗反轉錄病毒治療的人高出 50%，而目前正在服用該藥物的人患心臟病和中風等重大心血管疾病的風險比接受其他抗反轉錄病毒治療的人高出 42%。

導致慢性疾病的另一個可能因素是愛滋病毒對身體的影響，即使感染得到良好的控制。病毒仍然存在，激活免疫系統並引發低水平發炎。

賴斯表示，了解到抗病毒藥物或愛滋病毒引起的發炎可能會加速癌症和心血管疾病等疾病的發生，這可能是改變愛滋病毒感染者臨床篩檢和檢測這些疾病的實踐的一個原因。他從 AGEhIV 研究中得到證據顯示，在感染的早期階段，也許在開始治療之前，身體就會受到很大的損害。他說，這顯示需要對愛滋病毒感染高風險族群進行更好的篩檢，並儘早開始治療，以幫助減輕以後的健康問題。

一項名為 REPRIEVE 的大型臨床試驗有超過 7,500 名參與者參與，該試驗的一份令人鼓舞的報告顯示，服用他汀類藥物 (statin medication) 可使 HIV 感染者的心臟病發作、中風和其他心臟問題的發生率降低 35%。這項為期五年的試驗結果於 2023 年公佈，並已納入愛滋病毒感染者治療臨床指引。

米格爾是一位長期患者，他從 AZT 開始接受治療，他說醫生給愛滋病毒感染者的標準建議是盡可能健康地生活，以避免過早衰老和相關疾病。如今，他正在接受糖尿病治療，肛門癌的病情也處於緩解期。他不知道是愛滋病毒還是維持他生命的藥物導致了這些症狀，或者兩者都不是，但他也沒有多想。

他說：「我擁有美滿的婚姻、溫馨的家、養的狗和熱愛的工作」。「令人驚訝的是我還在這裡」。

本文最初於 2025 年 6 月 10 日發表在《Knowable Magazine》。 《Knowable Magazine》是《Annual Reviews》旗下的獨立新聞機構，《Annual Reviews》是一家非營利出版商，致力於綜合和整合知識，促進科學進步，造福社會。

可知雜誌 © 2025 Annual Reviews, Inc

HIV Medications: Did Fears About Side Effects Come to Pass?

Tammy Worth / June 16, 2025 / Knowable Magazine

Miguel, a 63-year-old Los Angeles teacher, recently marked the 38th anniversary of his diagnosis with HIV. The doctor had told him he would be dead in a couple of years. He lived fearful that each passing one might be his last. 

Miguel started to take AZT (azidothymidine), the first antiretroviral drug used to treat HIV and AIDS, and then moved to a succession of other drugs. While he was on one called Crixivan, he experienced hollowed cheeks and increased fat in his chin, characteristic of early HIV medications. He escaped other early effects: Severe headaches, muscle pain, insomnia, anemia and other blood disorders. “Gay men were talking about it being very harmful to the body,” says Miguel (not his real name, for privacy reasons). “But it was a crapshoot; if you take this terrible thing, at least you have a fighting chance.” 

The drugs saved many millions of lives, but some doctors wondered about long-term effects of the early medications. They saw lipid disturbances and severe neuropathy: Numbness, tingling, and pain in the limbs. Some predicted a future of early heart disease and heart attacks among gay men and others infected by HIV. 

Today it’s known that people with HIV receiving antiviral treatments do tend to have higher rates of certain chronic health conditions. But researchers still aren’t fully sure what causes what. Research has shown that some HIV drugs, particularly the early ones, increase certain risks, but so, too, does low-level persistence of the virus in the body. Sorting out the causes is important to monitoring and treating this group of patients, who now can expect to live a close-to-normal lifespan. 

More than 50 antiretroviral medicines, which keep HIV from replicating and spreading, are approved by the US Food and Drug Administration. They are generally taken as a regimen, combining two or three medications from different drug classes. 

People taking AZT, the first drug to be approved, often found themselves with a condition known as wasting, or involuntary weight loss of 10 percent or more. In contrast, some of today’s drugs appear to cause weight gain, says Kristine Erlandson, an infectious disease specialist at UC Health University of Colorado Hospital. In a 2024 report of 2624 HIV-positive people, published in Clinical Infectious Diseases, she found that the mean weight gain was almost 8 pounds in the first year of antiretroviral therapy. 

During roughly 9 years of follow-up, about 5 percent of participants were diagnosed with diabetes and 14 percent with metabolic syndrome (a group of conditions including obesity, low levels of “good” or HDL cholesterol, and high blood sugar), and 16 participants had a stroke. While some people have pronounced weight gain on the new HIV drugs, “there are many people on these medications that have a totally normal weight,” Erlandson says. “We don’t know who it will be that gains, or why.” 

More generally, researchers have linked HIV-positive people with a slate of conditions normally associated with advancing years: Cardiovascular disease, cognitive impairment, diabetes, and frailty. “In the early days of the epidemic, people were starting to scream that people with HIV were having premature aging,” says Peter Reiss, a former internal medicine doctor and infectious disease specialist at the Amsterdam University Medical Center. “But there was really no data to back that statement up.” 

To get answers, in 2010 Reiss and colleagues began a study called AGEhIV that followed 1146 people in Amsterdam over about 6 years. Just over half were HIV-positive, and a similar group without HIV made up the rest. 

The scientists found that people with HIV were indeed more likely to have hypertension, heart attacks, osteoporosis, kidney disease, and peripheral artery disease (where arteries in the legs and abdomen narrow, slowing blood flow). Nearly all of the HIV-positive participants were taking HIV medications, with near-undetectable levels of the virus, Reiss says, “so you’re really talking about what is happening in effectively treated HIV.” 

Reiss and colleagues also found a link to cancers not traditionally associated with infection by HIV, such as ones of the stomach, lungs, and blood. Of 38 people who died during the years of the study, 16 succumbed to such cancers, and all but one were in the HIV-positive group. 

Many other population studies have been conducted through the years, and findings generally align: People with HIV appear to have an increased risk of various chronic diseases, as well as an average life expectancy 5-10 years shorter than people who are HIV-negative. 

For example, a 2022 review of 47 reports on antiretroviral therapy reported that having HIV doubled the risk of cardiovascular disease and increased the risk of bone and muscle conditions like sarcopenia (a gradual loss of muscle mass and strength), depression and cancer. And a large US study published in 2020 found that in 2016, people without HIV could expect to live 9 more years on average than people with HIV. They also averaged more than 16 years free of other health conditions than the HIV group. 

In good news, the life expectancy gap was down dramatically, from a 22-year difference in the early 2000s, largely because of modern antiretrovirals and early treatment commencement, scientists think. 

What causes these differences? It’s important to know, because these disproportionate rates of chronic illness harm people’s lives and are costly, noted Anthony Fauci, former director of the National Institute of Allergy and Infectious Diseases, and colleagues in a 2019 opinion article in the journal JAMA. Monthly costs for treating someone with HIV plus cardiovascular disease or chronic kidney disease were $1400 to $5000 more per month than for someone with HIV alone, they wrote. 

Lifestyle is one contributing factor. People with HIV tend to have higher rates of smoking, alcohol use, depression and anxiety, says Reiss. But, he adds, this can’t account for all the increase in early onset of age-related conditions. 

Medication connections, meanwhile, continue to emerge. Abacavir, to name one example, has recently been linked to cardiovascular disease, says Priscilla Hsue, chief of cardiology at UCLA Health. At the 2024 AIDS Conference, researchers reported that people who had taken the drug had a 50 percent greater risk of major cardiovascular problems such as heart attack and stroke, and those currently taking it had a 42 percent higher risk compared to people on other antiretroviral treatments. 

Another possible contributor to chronic diseases is the effects of HIV on the body, even when the infection is well controlled. The virus is still there, activating the immune system and inducing low-level inflammation. 

Knowing that antiretrovirals or HIV-induced inflammation may hasten the onset of conditions like cancer and cardiovascular disease could be a reason to change clinical screening and detection practices of such conditions for people with HIV, Reiss says. He has evidence from the AGEhIV study that much damage is done to the body in the early stages of infection, perhaps before treatment commences. That argues for better screening of people at high risk of having HIV and for early treatment commencement to help mitigate health issues later, he says. 

One encouraging report from a large clinical trial known as REPRIEVE, involving more than 7500 participants, was that taking a statin medication reduced rates of heart attacks, strokes, and other cardiac problems among people with HIV by 35 percent. The five-year trial’s findings, published in 2023, have been incorporated into clinical guidelines for treating people with HIV. 

Miguel, the longtime patient who started with AZT, says the standard message from doctors for people with HIV is to live as healthily as possible to avoid premature aging and related conditions. Today, he is being treated for diabetes and is in remission for anal cancer. He can’t know if HIV or the drugs that sustain him, or neither, caused the conditions, but he does not give it much thought. 

“I have a great marriage, a lovely home; I have dogs and a job that I love,” he says. “The amazing thing is I am still here.”

This article originally appeared in Knowable Magazine on June 10, 2025. Knowable Magazine is an independent journalistic endeavor from Annual Reviews, a nonprofit publisher dedicated to synthesizing and integrating knowledge for the progress of science and the benefit of society. 

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