人類乳突狀病毒 (HPV) 增加了撒哈拉以南非洲婦女感染愛滋病毒的風險
資料來源：伊迪絲·馬加克 / 2022 年 4 月 13 日 / aidsmap news / 財團法人台灣紅絲帶基金會編譯
圖片來源： NIAID。知識共享許可。
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美國華盛頓大學西雅圖分校的 Gui Liu 博士及其同事在 AIDS 雜誌上發表的一項研究發現，在撒哈拉以南非洲的女性中，感染 HIV 的風險隨著人類乳突病毒 (HPV) 感染的數量而增加。每檢測到一種額外的 HPV 型別，愛滋病毒感染的風險就會增加 20%。
巢式病例對照研究還顯示，可透過疫苗預防的 HPV 病毒株感染會使感染 HIV 的風險增加一倍。作者認為，增加 HPV 疫苗接種覆蓋率可能會降低撒哈拉以南非洲婦女的 HIV 發病率。
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背景
撒哈拉以南非洲地區 14-25 歲的少女和年輕女性僅佔人口的 10%，但卻在 2017 年新增 HIV 感染病例中佔 25%。增加她們對 HIV 易感性的高度流行的生物學因素之一可能是 HPV ，導致子宮頸癌的性病感染(STI)。特別是在非洲，36% 的少女和年輕女性感染了 HPV。
性交過程中的 HIV 傳播主要發生在陰道（或肛門）的粘膜內層。正常情況下，黏膜內層的細胞緊密相連，形成一道保護屏障。即使在正常情況下，HIV 也可以越過這一屏障，但在人體對 HPV 的免疫反應過程中釋放的蛋白質可能會破壞或放鬆細胞之間的緊密連接，從而削弱屏障的完整性，使 HIV 更容易潛入。
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HPV 疫苗接種計畫正在撒哈拉以南非洲擴大推廣，以消除子宮頸癌並促進婦女和女孩的福祉。然而，儘管 HPV 疫苗具有出色的安全性，但對 HPV 疫苗的誤解繼續導致在需求上不理想狀態。喀麥隆和烏干達的一項研究發現，對不孕的恐懼是猶豫的主要原因，而在肯亞，25% 的父母會拒絕接種疫苗，因為他們認為女兒在接種疫苗後會出現濫交行為，同時也歸因於宗教領袖對社區的態度。肯亞多達 29% 的父母表示，他們不會為女兒接種疫苗，因為他們的宗教禁止她們接種疫苗。肯亞天主教醫生協會（KCDA）公開辯稱，疫苗「有副作用」，「貞潔的孩子不必擔心感染 HPV」。
儘管其他性傳染病感染 (STI) 在增加 HIV 風險方面的作用已得到充分證實，但有關 HPV 與 HIV 感染之間關聯的數據相對較少。為了評估這種關係，研究人員使用了來自陰道和口腔介入以控制流行 (the Vaginal and Oral Interventions to Control the Epidemic, VOICE) 的數據，這是一項在南非、烏干達和辛巴威進行的隨機對照試驗，評估有感染 HIV 風險的性活躍順性別女性PrEP對其之療效。
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VOICE 試驗於 2009 年至 2015 年期間進行，招募了 18 至 45 歲使用避孕措施且未懷孕的 HIV 陰性女性。參與者在入組時、年度追蹤時和有臨床病徵時接受了性傳播感染和陰道感染評估。他們還每月通過快速檢測進行 HIV 檢測，如果檢測呈陽性，隨後進行確認性西方墨點檢測。每六個月收集一次宮頸和陰道拭子，但並未對拭子進行即時 HPV 檢測。在 VOICE 試驗期間，HPV 疫苗並未廣泛使用，也未向參與者提供疫苗。
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研究
為了在 HPV 檢測和 HIV 感染之間建立明確的關係，病例對照分析的選擇標準包括在 HIV 陽性結果前 1 至 6 個月收集宮頸或陰道拭子樣本。
在 VOICE 研究期間感染 HIV 的 312 名參與者中，有 138 名符合納入標準。根據研究訪問、年齡和研究地點，每個病例都與來自 VOICE 的三個對照進行匹配。病例和對照在收案時平均年齡為 23 歲。
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HPV 感染以多種方式進行檢查：感染任何 HPV 類型、感染 14 種高風險類型中的任何一種、感染除 HPV 16 或 18 以外的任何高風險類型，以及感染任何低風險類型。為了檢查疫苗可預防的 HPV 類型與 HIV 風險之間的關係，研究人員還將暴露定義為感染二價疫苗（HPV 16 或 18）所針對的任何類型，感染四價疫苗所針對的任何類型（HPV 6、 11, 16, 18) 和感染九價疫苗靶向的任何類型 (HPV 6, 11, 16, 18, 31, 33, 45, 52, 58)。他們還評估了 HIV 感染與檢測到的 HPV 型別數量之間的劑量反應關係。
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為了確定風險估計值，研究人員調整了以下行為和人口統計因素：年齡、教育程度、保險套使用、性伴侶的數量、過去一年中的性交易、當前的主要伴侶、參與者或其伴侶在他們的伙伴關係之外有其他關係、性傳播感染、單純皰疹病毒2型 (HSV-2) 和其他陰道感染。
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HPV感染與HIV感染的關係
無論 HIV 狀態如何，研究樣本中 HPV 感染的流行率都很高，在 84% 的病例和 65% 的對照組中檢測到任何 HPV 類型的感染。病例平均感染 3 次 HPV，而對照組平均感染 1.9 次。
了解更多：人乳突病毒 (HPV) 和生殖器疣
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與未感染高危 HPV 相比，感染高危 HPV的 HIV 風險高 2.7 倍，感染低危 HPV與無低危感染相比高 1.8 倍。
對於疫苗可預防的 HPV 感染，HIV 感染與九價疫苗和四價疫苗所針對的任何類型的感染有關。 HIV 感染風險隨著感染單一 HPV 類型 (1.9) 而升高，並隨著檢測到的 HPV 類型的數量而增加。兩到三種 HPV 類型為 2.2 倍，四種或更多類型為 4.1 倍。每檢測到一種額外的 HPV 類型，愛滋病病毒感染的風險就會增加 20%。
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結論
「我們發現同時感染多種 HPV 型別會顯著增加 HIV 風險。具體來說，每檢測到一種額外的 HPV 類型，感染 HIV 的風險就會增加 20%」，研究人員總結道。
「在 HPV 和 HIV 感染負擔高的國家，廣泛實施 HPV 疫苗接種九價或四價疫苗可能具有同時降低女性感染 HIV 和宮頸癌風險的雙重好處」。
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參考文獻
Liu G等人。人類乳突病毒感染的盛行增加了非洲婦女感染愛滋病毒的風險：推進人類乳突病毒免疫接種的論點。 愛滋病 36：257-265，2022。
DOI: 10.1097/QAD.0000000000003004
HPV increases the risk of HIV acquisition among women in sub-Saharan Africa
Edith Magak / 13 April 2022
Image by NIAID. Creative Commons licence.
A study by Dr Gui Liu of the University of Washington, Seattle and colleagues published in the journal AIDS found that among women in sub-Saharan Africa, the risk of HIV acquisition increased with the number of human papillomavirus (HPV) infections. With each additional HPV type detected, HIV risk increased by 20%.
The nested case-control study also showed that infection with HPV strains that are preventable by vaccines doubled the risk of HIV acquisition. The authors suggest that increasing HPV vaccination coverage could potentially reduce HIV incidence in sub-Saharan African women.
Background
Adolescent girls and young women aged 14–25 years in sub-Saharan Africa represent only 10% of the population but accounted for 25% of new HIV infections in 2017. One of the highly prevalent biological factors that increase their susceptibility to HIV may be HPV, a sexually transmitted infection (STI) which causes cervical cancer. In Africa specifically, 36% of adolescent girls and young women have HPV.
HIV transmission during sex occurs primarily across mucosal linings in the vagina (or anus). Normally, the cells in mucosal linings are tightly interlocked, forming a protective barrier. Even under normal conditions, HIV can cross this barrier, but it is possible that proteins released during the body’s immune response to HPV may disrupt or loosen the tight connections between cells, weakening the barrier’s integrity and making it easier for HIV to sneak across.
HPV vaccination programmes are being scaled up in sub-Saharan Africa in order to eliminate cervical cancer and promote well-being among women and girls. However, misconceptions about HPV vaccines continue to contribute to sub-optimal demand despite their excellent safety profile. A study in Cameroon and Uganda found that fear of infertility was the major reason for hesitancy, while in Kenya 25% of parents would reject the vaccination because of perceived promiscuous behaviours in their daughters after vaccination. Religious leaders also contribute to community attitudes. Up to 29% of parents in Kenya said they would not vaccinate their daughters because their religion prohibits them. The Kenya Catholic Doctors Association (KCDA) has publicly argued that the vaccine “has adverse effects” and that “children who are chaste need not worry about contracting HPV”.
Although the role of other STIs in increasing HIV risk is well established, data on the association between HPV and HIV acquisition are relatively scarce. To evaluate this relationship, the researchers used data from the Vaginal and Oral Interventions to Control the Epidemic (VOICE), a randomised controlled trial in South Africa, Uganda and Zimbabwe which assessed the efficacy of PrEP in sexually active cisgender women at risk for acquiring HIV.
The VOICE trial was conducted between 2009 and 2015, and enrolled HIV-negative women aged 18–45 years who were using contraception and were not pregnant. Participants were assessed for STIs and vaginal infections at enrollment, at annual follow-up visits and when clinically indicated. They also underwent HIV testing monthly with a rapid test, which, if positive, was followed by a confirmatory western blot test. Cervical and vaginal swabs were collected every six months, though the swabs were not tested for HPV in real time. During the VOICE trial, HPV vaccines were not widely available and participants were not offered them.
The study
To establish a clear relationship between the detection of HPV and HIV acquisition, the selection criteria for the case–control analysis included having a stored cervical or vaginal swab specimen that was collected between one and six months before a HIV-positive result.
Of the 312 participants who acquired HIV during the VOICE study, 138 met the inclusion criteria. Each case was matched to three controls from VOICE, based on study visit, age and study site. Cases and controls were on average 23 years old at enrollment.
HPV infection was examined in several ways: infection with any HPV type, infection with any of the 14 high-risk types, infection with any high-risk type other than HPV 16 or 18, and infection with any of the low-risk types. To examine the association of vaccine-preventable HPV types on HIV risk, researchers additionally defined exposure as infection with either of the types targeted by the bivalent vaccine (HPV 16 or 18), infection with any type targeted by the quadrivalent vaccine (HPV 6, 11, 16, 18) and infection with any type targeted by the nonavalent vaccine (HPV 6, 11, 16, 18, 31, 33, 45, 52, 58). They also evaluated the dose–response relationship between HIV acquisition and the number of HPV types detected.
To determine estimates of risk, the researchers adjusted the following behavioural and demographic factors: age, education, condom use, number of sex partners, having transactional sex in the past year, having a current primary partner, the participant or her partner having other relationships outside of their partnership, STIs, HSV-2, and other vaginal infections.
Relationship between HPV infection and HIV acquisition
The prevalence of HPV infection was high in the study sample regardless of HIV status, with infection with any HPV type detected in 84% of cases and 65% of controls. Cases had an average of three HPV infections, whereas controls had an average of 1.9 infections.
Find out more: Human papillomavirus (HPV) and genital warts
The risk of HIV was 2.7 times higher with a high-risk HPV infection compared with no high-risk HPV infection, and 1.8 times higher with a low-risk HPV infection compared with no low-risk infection.
For vaccine-preventable HPV infections, HIV acquisition was associated with infection with any of the types targeted by the nonavalent vaccine and the quadrivalent vaccine. The risk of HIV was elevated with infection with a single HPV type (1.9) and increased with the number of HPV types detected. For two to three HPV types, 2.2 times, and for four or more types, 4.1 times. With each additional HPV type detected, HIV risk increased by 20%.
Conclusion
“We found that concurrent infection with multiple HPV types significantly increased HIV risk. Specifically, the risk of HIV acquisition increased by 20% with each additional HPV type detected”, the researchers conclude.
“In countries with a high burden of both HPV and HIV infections, widespread implementation of HPV vaccination with the nonavalent or the quadrivalent vaccines may potentially have the dual benefit of concurrently reducing risk for HIV and cervical cancer among women.”
References
Liu G et al. Prevalent human papillomavirus infection increases the risk of HIV acquisition in African women: advancing the argument for human papillomavirus immunization. AIDS 36: 257-265, 2022.
DOI: 10.1097/QAD.0000000000003004
War and infectious diseases: brothers in arms
On Feb 24, 2022, Russia invaded Ukraine. The invasion has resulted in death, injury, and the displacement of people. Even if ongoing peace talks bring a cessation to hostilities, Ukraine will likely continue to suffer for years to come. War is always accompanied by infectious disease outbreaks, and Ukraine will likely be no exception.
The Russian invasion has severely damaged Ukraine’s health-care infrastructure, with WHO confirming at least 70 Russian attacks on health-care facilities across Ukraine. Such attacks, combined with the destruction of roads, bridges, and public transportation networks, prevent citizens from receiving medical help, increasing the risk of long-term injury and infection. And, once the fighting has stopped, reduced access to healthcare will hamper a population trying to rebuild.
Specialist services have also been disrupted. Russian military assaults have forced the closure of the AIDS Healthcare Foundation’s HIV clinics in Kharkiv and Mariupol, raising the risk of treatment interruption in people with HIV in these cities. Interruption is associated with an increased risk of developing drug-resistant HIV, narrowing treatment options and increasing transmission. Tuberculosis control efforts have been similarly impacted. Those suffering from tuberculosis, who have been fleeing conflict zones to reach safer regions of Ukraine, risk discontinuity of treatment, increasing risk of death, transmission, and emergence of drug resistance. SARS-CoV-2 will also spread as physical distancing is made difficult in underground shelters and vaccination efforts are disrupted by the war. Vaccination efforts were already low before the invasion, with only 35% of Ukraine residents fully vaccinated against SARS-CoV-2. This low vaccination rate is just one of the health concerns that countries welcoming fleeing Ukrainians need to consider. Ukrainian refugees are also likely to be more vulnerable to infection given their living conditions during their escape.
These are current infectious disease concerns, and we can, sadly, look to other conflicts to identify possible long-term consequences. Syria has been gripped by civil war since 2011. In 2016, during the 6-month Siege of Aleppo, pro-government forces cut supply lines and attacked medical facilities, leaving a city of 250000 short of medicine and food. One of the outcomes of the civil war and the siege has been, in 2017 and 2018, a measles outbreak across northern Syria, including Aleppo, after the disease had been absent in the country since 1999. A similar story could play out in Ukraine. In October 2021, Ukraine reported a case of paralytic polio prompting the government to begin vaccinating 100000 unprotected children, a rollout halted by the invasion.
The war in Ukraine hopefully will not become a protracted conflict. As with Syria, the longer a conflict goes on, the more resources are diverted from health towards warfare. In Afghanistan, after 20 years of US (and their allies) military presence in the country, 2 million children are malnourished. Lack of food weakens the immune system and is part of the reason Afghanistan is currently trying to rapidly vaccinate its population to halt their own measles outbreak. Yemen, suffering from a civil war since 2014, has also seen a similar redistribution of resources. 4 million Yemenis have been internally displaced with reduced access to suitable water and sanitation services, increasing the risk of diarrhoeal diseases. In 2017, a cholera outbreak with a suspected 2·5 million cases was responsible for 3868 deaths. Before the war, cholera had been absent from Yemen.
The long-term health of Ukraine refugees should also be of concern, escpecially if they are housed in refugee camps for prolonged periods. In August 2017, fleeing violence perpetrated by the Burmese military, hundreds of thousands of Muslim Rohingya people fled Burma. As of Feb 2021, over 870000 Rohingya have been provided shelter in Bangladesh, a staggering 719000 in the Kutupalong Refugee Camp (and associated extension camps). Individuals crowded in such a location, with improper sanitation, are at increased risk of diseases such as malaria and dengue, a situation worsened by Bangladesh’s monsoon season that runs from June to October.
Other conflicts highlight the risks that the Ukrainian people face but given the international response in support of Ukraine hopefully a large number of them can be avoided. But, should they be avoided in Ukraine, we should also reflect on the West’s tolerance of infectious diseases and war in the above, nonWestern, and predominantly non-white countries. ■ The Lancet Infectious Diseases