In search of the neoantigen
The Stages Of HIV Infection
Key pointsMost descriptions of the stages of HIV infection describe the natural history of HIV, in other words how, over time, the disease progresses in people who are not taking HIV treatment. They show how HIV progressively attacks and weakens the immune system, eventually leading to AIDS (acquired immune deficiency syndrome).
This is not what happens to people who take effective HIV treatment (antiretroviral therapy). These medications can keep the virus under control and stop a decline in health. They profoundly change the course of infection.
The following description of the stages of HIV infection takes account of the impact of HIV treatment.
Seroconversion and acute HIV infectionIn the first few weeks after infection with HIV, some people have a short flu-like illness that is called a 'seroconversion illness'. This coincides with the period during which the body first produces antibodies to HIV. The most commonly experienced symptoms are fever, swollen glands, muscle aches and tiredness.
The severity of symptoms at this stage can vary considerably between people – they can be so mild as to go unnoticed, or so severe that admission to hospital is needed. They usually go away within two to three weeks.
This early stage of HIV infection is called acute HIV infection. The US public health agency the Centers for Disease Control and Prevention (CDC) describes it as stage 0.
During acute infection, there are very high levels of HIV in the body (a high viral load), which means that the risk of passing HIV on is higher than at other times.
You can start HIV treatment during acute infection. HIV treatment lowers the amount of virus in the body, which allows the immune system to strengthen and helps prevent illnesses from occurring. Starting HIV treatment in this early phase may have particular benefits in terms of preserving the immune system.
People who start HIV treatment go straight to the 'chronic' stage of infection, described towards the end of the page.
Asymptomatic HIV infectionOnce you have passed through the primary infection phase, you usually enter a phase in which you don't have any symptoms or obvious health problems, even if you are not yet taking HIV treatment. This period can last for several years.
In the classification system of the World Health Organization (WHO), this is stage 1 (asymptomatic). In the slightly different system of the CDC, it is also described as stage 1 (but defined in terms of a CD4 cell count above 500).
'Asymptomatic' means 'without symptoms'. It does not mean HIV is not having an effect on your immune system, just that there are no outward signs or symptoms. Blood tests will show how active HIV is inside the body and the impact it is having on your immune system. The viral load test will usually show that the virus is replicating, while the CD4 cell count will give a rough indication of the strength of your immune system.
The sooner you start to take HIV treatment, the sooner you can benefit from it. If you do so, you can skip the next two stages and go straight to the 'chronic' stage of infection, described towards the end of the page.
Symptomatic HIV infectionThe longer you live with HIV without treatment, the further your CD4 cell count will fall. This is a sign that your immune system is being weakened and that there is a greater risk of developing symptoms.
Glossary chronic infectionWhen somebody has had an infection for at least six months. See also 'acute infection'.
immune systemThe body's mechanisms for fighting infections and eradicating dysfunctional cells.
symptomAny perceptible, subjective change in the body or its functions that signals the presence of a disease or condition, as reported by the patient.
acute infectionThe very first few weeks of infection, until the body has created antibodies against the infection. During acute HIV infection, HIV is highly infectious because the virus is multiplying at a very rapid rate. The symptoms of acute HIV infection can include fever, rash, chills, headache, fatigue, nausea, diarrhoea, sore throat, night sweats, appetite loss, mouth ulcers, swollen lymph nodes, muscle and joint aches – all of them symptoms of an acute inflammation (immune reaction).
effectivenessHow well something works (in real life conditions). See also 'efficacy'.
Symptoms may include skin disorders, prolonged diarrhoea, night sweats, thrush, bacterial pneumonia, fatigue, joint pain, and weight loss. Opportunistic infections that the immune system is normally able to fight off may begin to occur.
In the WHO classification, this is stage 2 (mild symptoms) and stage 3 (advanced symptoms). In the CDC system, it corresponds with stage 2 (a CD4 count between 200 and 500).
Many people only get tested for HIV and receive their HIV diagnosis at this stage. This may be described as a 'late diagnosis'. If you are diagnosed late, it means that you have already had HIV for several years without taking treatment.
Nonetheless, you can start to take treatment now and it will still be effective. It will strengthen your immune system, reduce the amount of HIV in your body and prevent illnesses from occurring. You can skip the next stage and move on to 'chronic' HIV infection.
AIDSIf somebody goes a very long time without treatment, the most serious stage of infection can occur. This is known as AIDS (acquired immune deficiency syndrome) or advanced HIV disease. It refers to a range of serious illnesses that people may get when HIV has significantly weakened their immune system.
For WHO, this is stage 4 (severe symptoms). In the CDC system, it is stage 3 (a CD4 count below 200).
Thanks to effective HIV treatment, most people with HIV never develop AIDS. The syndrome most often develops in people who are diagnosed at a very late stage and so were living with untreated HIV for many years.
If someone develops an AIDS-defining illness, this doesn't mean that they are on a one-way path to illness and death. With the right HIV treatment and care, many people who have been diagnosed as having AIDS recover from their AIDS-related illness and go on to have long and healthy lives. They move on to the following stage: chronic HIV infection.
Chronic HIV infection with antiretroviral treatmentIf you take effective HIV treatment, you can live with HIV as a chronic, manageable condition. A 'chronic' health condition is one which continues for a long period of time.
This stage is not included in most descriptions of the stages of infection, which only describe disease progression in the absence of treatment.
However, most people living with HIV who have access to good healthcare are living with HIV as a chronic condition – and will continue to do so for the rest of their lives. They are unlikely to fall ill or die as a direct result of HIV.
In order to reach this stage and to remain in it, you need to take HIV treatment and continue to take it, on an ongoing basis. These medications reduce levels of HIV in your body and strengthen the immune system. This usually prevents the symptoms and opportunistic infections described above from occurring.
Some immune system damage and inflammation does persist. This is one of the reasons why people living with chronic HIV are more vulnerable to some other health conditions, including heart disease, diabetes and cancer.
One of the benefits of effective HIV treatment is that is stops HIV from being passed on. Treatment drastically reduces the amount of HIV in body fluids to the point where there is not enough HIV to transmit the virus to sexual partners.
The chronic infection phase can last for decades. People who start HIV treatment as soon as possible, are able to stick with it and have access to good healthcare are likely to have a similar life expectancy to their peers who don't have HIV.
Trial Demonstrates One-year Progression-free Survival In 94% Of Patients With Stage 3 Or 4 Classic Hodgkin Lymphoma
A Phase 3 trial has demonstrated that patients with advanced stage (3 or 4) classic Hodgkin lymphoma who underwent initial treatment with nivolumab, a PD-1 checkpoint inhibitor, and AVD chemotherapy (N-AVD) had a significantly lower risk of their cancer getting worse than patients treated with brentuximab vedotin, a monoclonal antibody, and AVD (BV-AVD) a year after starting treatment.
Ninety-four percent of adolescent and adult patients in the N-AVD group had progression-free survival compared with 86% in the BV-AVD arm. N-AVD was also well-tolerated as there were few serious immune-related side effects in the S1826 trial. The median follow-up was 12.1 months.
These late-breaking findings will be presented by City of Hope's Alex Herrera, M.D., at ASCO's 2023 Plenary Session, June 4, at 2:53 p.M. CT in Hall B1 and will be featured in the official ASCO press program.
Lead investigator on the study, Herrera is chief of the Division of Lymphoma at City of Hope, one of the largest cancer research and treatment organizations in the United States, and is an investigator with the SWOG Cancer Research Network.
"The results are remarkable. The combination of nivolumab and chemotherapy is potent and safe in patients with Stage 3 or 4 classic Hodgkin lymphoma as an initial treatment," said Herrera, "The therapy is poised to be a standard for treatment of advanced Hodgkin lymphoma. This is indeed great news for patients with this cancer as there is another effective and safe treatment option for them."
Georgie Garabet, 43, of Glendora, California, was one of the patients who participated in the trial. When Garabet began to feel sick in early 2020, he was a 40-year-old father of two children under the age of 3. His symptoms included uncontrollable itching all over his body and severe weight loss. After a few trips to emergency rooms and to his primary care doctor, he was eventually diagnosed with Stage 3 Hodgkin lymphoma.
"I panicked when I heard the word cancer," Garabet said. At the same time, he was relieved to know what was causing his symptoms.
Garabet met Herrera and instantly felt he was in good hands. "He explained everything so well," he added. Garabet enrolled in the trial. After his first infusion, he felt exhausted but that was the worst he felt during treatment. After only four infusions, he was in remission. He was advised to continue the treatment in case any cancer lingered, and he did. "Now when people tell me they have cancer, I tell them not to panic. There are a lot of cures now," he added.
The S1826 trial, supported by the NCI and led by SWOG, is the largest classic Hodgkin lymphoma study ever conducted in the NCI's National Clinical Trials Network and is also representative of a diverse patient population. About a quarter of the enrolled patients were Black or Hispanic. A partnership with the Children's Oncology Group (COG) helped ensure the trial included young adolescents, and a quarter of enrolled patients were younger than 18 years old. Nearly two-thirds of all patients had Stage 4 cancer.
"This study speaks to the power of the National Clinical Trials Network and is an excellent example of the transformative work that the NCI funds," said Jonathan Friedberg, M.S., M.M.Sc., senior author of the study, chair of the SWOG Cancer Research Network's lymphoma committee and director of the Wilmot Cancer Institute at the University of Rochester.
"Hodgkin lymphoma is not a common disease and the NCTN enabled a large network of more than 200 pediatric and adult community providers and academic medical centers to work together. Because of that, we were able to get data very quickly and directly impact patient care. This was a critical investment in cancer research and treatment."
Patients with Stage 3 or 4 classic Hodgkin lymphoma who had not been previously treated and were age 12 or older were eligible for the trial. Of a total of 976 eligible patients, 489 were enrolled in the N-AVD arm (nivolumab plus Adriamycin, vinblastine and dacarbazine), while 487 were part of the BV-AVD group. Each group received six infusion cycles of each combination therapy.
As expected with combination chemotherapy, the most common side effects included gastrointestinal and hematologic toxicities, and fatigue. However, less than 1% of patients needed radiation after trial treatment, which is a dramatic reduction in the proportion of patients being initially treated for Hodgkin lymphoma who need radiation, especially among pediatric patients.
"The ability to maintain high rates of relapse-free survival with minimal use of radiation therapy in children with newly diagnosed advanced stage Hodgkin lymphoma will be a paradigm shift," said Sharon Castellino, M.D., M.Sc., chair of the COG Hodgkin lymphoma committee and director of the Leukemia and Lymphoma Program at the Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Winship Cancer Institute at Emory University.
Brentuximab vedotin was the first antibody–drug conjugate developed for classic Hodgkin lymphoma. Several studies have demonstrated that incorporating the therapy into frontline treatment improves progression-free survival and overall survival. Despite improved outcomes, there are still serious side effects; relapses can occur.
"There is definitely a need to improve frontline therapies for Hodgkin lymphoma, particularly because a disproportionate number of patients with this disease are teens and young adults," Herrera added.
PD-1 checkpoint inhibitors are a powerful and growing form of immunotherapy used to treat melanoma, kidney cancer, head and neck cancers, relapsed or difficult to treat Hodgkin lymphoma and other cancers. The PD-L1 protein is expressed on Hodgkin lymphoma tumor cells and aids the cancer by signaling to immune cells, such as T cells, to stop working against tumors.
Checkpoint inhibitors block the PD-L1 protein to help the immune system and, specifically, T cells, do what they're designed to do, eradicate cancer. In this study, adding nivolumab to chemotherapy worked so well that some patients experienced remission after only a few treatments.
Next steps for the trial include following patients to measure the durability of progression-free survival, overall survival and other patient outcomes.
Provided by SWOG Cancer Research Network
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Africa: Analysis - Is HIV/Aids Misinformation And Denialism On The Rise Again? How To Counter Persistent Myths
Well-worn untruths about HIV/Aids took a backseat during the Covid-19 pandemic. But vigilance against Aids denialism is important, particularly in Africa where access to accurate information and inclusive healthcare is still patchy.
Since the discovery of the human immunodeficiency virus (HIV) in the 1980s, widespread myths about HIV infection and claims about natural cures have continued to spread.
Similar to what Africa Check has seen with Covid-19 and Ebola, the outbreak of a disease often provides fertile ground for health misinformation to thrive, because of the resulting fear and panic.
Whenever there is doubt and confusion, people are willing to exploit it, especially for financial gain, according to Dr Alastair McAlpine, an infectious disease specialist in the Infection Prevention and Control department of British Columbia Children's Hospital Research Institute in Canada.
"When people are angry and fearful, they are more willing to listen to people offering easy solutions or misinformation," he told Africa Check.
Scientific data taken out of context, medical jargon and pseudo-scientific language can also cause confusion and doubt.
To make matters worse, when health misinformation is spread by decision makers and influential people, its reach increases. One of the most prominent examples of this in Africa was when former South African president Thabo Mbeki claimed, while in office, that HIV did not cause acquired immunodeficiency syndrome (Aids).
Mbeki served from 1999 to 2008.
Infection with HIV has been identified as the underlying cause of Aids. The virus progressively weakens the immune system, leading to a range of symptoms and infections. The term Aids refers to the most advanced stages of HIV infection. (Note: Read more about this in our back-to-basics factsheet on HIV/Aids here).
Although the time between becoming infected with HIV and developing Aids varies from person to person, the majority of people with HIV who are untreated will develop symptoms of Aids within eight to 10 years.
It is widely accepted that Mbeki's claims delayed access to life-saving antiretroviral (ARV) treatment for those who needed it. Communities who were oblivious to the risk failed to take adequate precautions, research shows.
The re-emergence of HIV/Aids misinformation
"We know that HIV causes Aids. That's 100% certain," Prof Francois Venter, executive director of Ezintsha Research Centre at the University of the Witwatersrand (Wits) in Johannesburg, told Africa Check. The organisation focuses on clinical and medical technologies research for chronic diseases, including HIV and Aids.
But despite clear evidence of the link between HIV and Aids and outrage from researchers and the public, Mbeki continues to express his doubts. In a lecture at the University of South Africa in September 2022, the former president said "the questions I raised then, I'm still raising them today".
"Aids is not a disease, it is a syndrome," he continued. Parts of his speech were broadcast on national television.
"You can't say one virus causes all of these illnesses" or syndromes. "What you can say is that this virus impacts negatively on the immune system," he said.
Over the years, Africa Check has debunked some of the most popular falsehoods about the disease, including that HIV was invented to reduce the population of Africa, that herbal remedies can cure HIV, and, more recently, that "monkeypox is actually acquired immunodeficiency syndrome, or Aids".
In early 2023 a familiar anti-vaccination rumour began to spread again on social media, claiming that people vaccinated against Covid-19 were developing "Aids-like symptoms".
"What's worrying is that the Covid-19 denialists are very powerful and they look exactly like HIV denialism looked 15 years ago," Venter said.
The decades-long trajectory - and cost - of HIV denialism in South Africa has been widely documented.
What are the risks of persistent health misinformation online? And what strategies should science communication adopt to counter persistent denialism?
HIV/Aids misinformation leads to risky behaviour
While some misinformation may be harmless, health misinformation or unsupported claims often pose a serious threat by misleading the public.
According to the latest data from the Joint United Nations Programme on HIV/Aids (UNAids), there were 38.4 million adults and children living with HIV worldwide in 2021. About 55% of all people living with HIV that year lived in East and Southern Africa.
Source: https://aidsinfo.Unaids.Org
In Africa, Aids is a greater challenge in low-income communities due to limited access to HIV/Aids information.
For example, a 2013 study on socio-economic inequality and HIV in South Africa highlighted that many who "did not test for HIV infection did so because of misconceptions about the disease".
Incorrect or a lack of information about HIV/Aids was also been linked to delays in people with the virus starting antiretroviral treatment in Malawi. Some of the beliefs that influenced late or no treatment uptake were the misconceptions that HIV is a death sentence and that treatment should only be taken when you are seriously ill, the 2011 study revealed.
Although ARVs are not a cure for HIV or Aids, there is strong evidence that they improve the quality of life of people living with the virus, and when the viral load, or the amount of HIV in bodily fluids, is suppressed, transmission from one person to another becomes less likely.
Based on his work in health systems research and antiretroviral treatment, Venter told Africa Check that he had observed a distinct pattern among groups of people who consistently delayed seeking treatment. These "non-uptakers" often arrived for HIV/Aids treatment at a very late stage because they were in denial about their health status, he said.
"We see this particularly among men who don't want to be on tablets for the rest of their lives, or who don't want to admit that they're ill," Venter said.
HIV/Aids stigma creating an information vacuum
Minorities are also a community of concern in Africa. The criminalisation of homosexuality has, for example, been identified as a major contributor to the spread of HIV misinformation.
It creates a culture of fear and secrecy around same-sex relationships, making it difficult for individuals to access accurate information about prevention and treatment.
The International Lesbian, Gay, Bisexual, Trans and Intersex Association's LGBTQI rights database recorded that at time of publication there were 62 countries that criminalised consensual same-sex intimate acts. Half of these countries were in Africa.
LGBTQI+ stands for lesbian, gay, bisexual, transgender, queer and intersex.
A 2021 UNAids report warned that outlawing homosexuality and sex work had a major impact on peoples' access to healthcare and on the quality of health information they received.
The report said: "Where same-sex sexual relationships, sex work and drug use were criminalized, levels of HIV status knowledge and viral suppression among people living with HIV were significantly lower than in countries that opted not to criminalize them".
Similar findings were made in a 2014 study that tracked LGBTI-focused discussions in Africa. Here 46% of participants said that in the absence of targeted health campaigns on the LGBTQI+ experience from official sources, they relied on sexual health information from the internet. This information vacuum left many vulnerable to misinformation.
Another concern raised by participants was that people in environments where their sexual identity was criminalised often did not fully disclose their sexual behaviour with health professionals for fear of homophobic treatment.
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"Conspiracy theories and misinformation thrive in the shadows, along with shame and fear," McAlpine told Africa Check.
"We must continue to promote the message that there is no shame in having HIV, no shame in being on therapy, no shame in having questions or concerns. Where there is an open environment of love and acceptance, misinformation struggles to take root."
Simplified science communication key to fighting Aids misinformation and denialism
In 2015, sociology professor David Dickson of Wits University explored how competing HIV/Aids information - scientific and alternative - was received by some HIV-positive township residents in South Africa.
"An asymmetric contest is taking place over Aids beliefs," he said, and those involved in HIV/Aids education needed to "adopt more humility towards the people that we seek to help but do not understand".
Although simply providing people with information on how they should behave might not be enough to change behaviour, McAlpine urged government, scientists and storytellers to inform the public correctly without overwhelming them.
"We also need a populace that is educated to understand the limits and uncertainty of cutting-edge science," he told Africa Check.
Venter stressed the importance of health literacy among journalists and said more funding was needed in this area. This includes knowing how to write about HIV/Aids. Research by fact-checking organisations, including Africa Check, has shown that targeted approaches are more effective than general messaging. It is therefore important to tailor messages to specific audiences.
The fight against Aids misinformation and denialism requires the creation of accurate, simplified and publicly available information that is tailored to people's experiences.
Then communities will have resources to challenge harmful myths when they come across them.
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