HIV

Early research suggests cancer drug could help flush HIV from its hiding spots

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When a resting immune cell that is latently infected with HIV gets reactivated, the cell starts producing HIV virions (red) that bud and release from the cell (blue).NIAID/NIH

Antiretroviral therapy, the standard treatment for HIV, can remove any trace of the virus from the blood, but a hidden reservoir of HIV persists in patients who are in treatment. That means patients are never truly cured and need to be on HIV drugs for the rest of their lives.

Researchers have yet to discover a way to eliminate the virus in its latent stage, but new, early-stage research suggests a landmark cancer drug — pembrolizumab, also known as Keytruda — may be able to help. In a study published Wednesday in Science Translational Medicine, researchers looked at 32 patients that had both cancer and HIV and found that pembrolizumab, which revives the immune system and encourages it to attack tumors, also has the ability to flush HIV out of its hiding spot in immune cells.

“This is an exciting advance,” Adeeba Kamarulzaman, the president of the International AIDS Society, said in a statement. She was not involved in the study. “Being able to stop HIV from hiding is an important part of finding an HIV cure.”

HIV attacks the immune system by infecting white blood cells known as T cells. Without antiretroviral drugs, the virus will proliferate wildly through the body, obliterating the immune system and eventually leading to the patient’s death. There are effective treatments for HIV that can stop the virus from replicating and give the immune system a chance to recover.

“But treatment can’t clear latent virus,” explained Sharon Lewin, an HIV researcher at the University of Melbourne and the senior author on the study. “And you always end up with exhausted T cells.”

These cells weaken the immune system and make it harder for it to fight diseases. Exhausted T cells often make a molecule called PD1, which stands for programmed death 1, a compound that suppresses the immune system and puts immune cells in a state of stupor. At the same time, PD1 can cause HIV to go quiet as well.

“PD1 causes a bit of trouble in HIV,” Lewin said. “It means you have an exhausted immune system that can’t clear [infected] cells, but you basically also silence the virus and put it in a latent form. So, you find a lot of these latent viruses inside cells that express PD1.”

That’s where the pembrolizumab comes in. The drug, first approved by the FDA in 2014 for use against advanced melanoma, binds to PD1 and takes it out of play. In cancer, this revs the immune system up to destroy tumor cells. It’s also made the drug a blockbuster and one of the most effective treatments for a range of cancers. In HIV, it may also help the immune system hunt down the last vestiges of HIV while also disrupting the virus’ ability to hide. “It has the potential to be a double whammy,” Lewin said.

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But testing the drug’s potential in HIV treatment poses challenges, because pembrolizumab and similar cancer immunotherapy drugs can have severe toxic side effects. Boosting the immune system with them is a double-edged sword. They can lead immune cells to kill tumors, but they can also cause the immune system to become overactive and lash out against the body’s healthy tissues, too.

“It’s challenging to give anti-PD1 drugs to people who don’t have cancer. There have been small studies, but they were stopped because of the side effects,” Lewin said.

So Lewin and her collaborators at the Fred Hutchinson Cancer Research Center had to find people who were both on antiretroviral therapy for HIV and were already being treated with pembrolizumab for cancer. They found 32 individuals who fit the bill and tracked levels of HIV in their blood throughout the course of their treatment.

Patients received an infusion of pembrolizumab every three weeks for up to 105 weeks, depending on how they responded to the drug. During that time, researchers regularly collected blood and analyzed it for HIV genetic material.

After the first infusion of pembrolizumab, the team began finding HIV genetic material in the patients’ blood, suggesting the drug was forcing the virus out its sanctuary and making it again vulnerable to the antiretroviral treatment and the body’s natural defenses. But, Lewin added, it wasn’t enough to free the patient of HIV entirely.

“It released the brakes on the virus, and now they’re visible to the immune system,” Lewin said. “But this is just a proof of concept. Anti-PD1 on its own repeatedly didn’t get rid of the reservoir.”

Still, it’s an important step toward finding a cure to HIV, said Steven Deeks, a professor of medicine at the University of California, San Francisco, and an HIV expert who worked on the study with Lewin. For decades, scientists looked for a powerful weapon against the latent reservoir of HIV that can finish the infection off once and for all.

“But we now have this road map saying, ‘OK, let’s try low doses. Let’s try other ways to manipulate the system in the same pathway,’” Deeks said. “And that’s why this is an important advance.”

Experts said far more research is needed to figure out where the road map leads.

“It makes us more enthusiastic about cure efforts, but I would not say we are close,” said Shyam Kottilil, an infectious disease physician and professor at the Institute of Human Virology at the University of Maryland School of Medicine. Kottilil, who was not involved in the research, added that ” major concern is safety of these agents in people with HIV without cancer.”

Because drugs like pembrolizumab can have such severe toxicity, scientists must see if there’s a dose that can effectively do the job without causing severe side effects or death. And more broadly, scientists must still understand whether and how drugs like pembrolizumab might play a role in treating HIV, and find the best way to use these drugs to fully clear the virus from the body.

That work has already started, Lewin said, including a planned study to give a low level of pembrolizumab to patients living with HIV who don’t also have cancer. It’s possible that study might yield better results, too, she said, since the cancer may have interfered with the body’s ability to take full advantage of the drug’s effect on HIV.

“There’s a lot of avenues being tested now,” she said.

New clinical trial will test three mRNA vaccine candidates for HIV

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The National Institute of Allergy and Infectious Diseases announced Monday that it has initiated a phase 1 clinical trial of three experimental messenger RNA HIV vaccines.

The study will be conducted by NIAID-funded HIV Vaccine Trials Network (HVTN), which is based at the Fred Hutchinson Cancer Research Center in Seattle.

Source: Adobe Stock

Anthony S. Fauci

“Finding an HIV vaccine has proven to be a daunting scientific challenge,” NIAID Director Anthony S. Fauci, MD, said in a press release. “With the success of safe and highly effective COVID-19 vaccines, we have an exciting opportunity to learn whether mRNA technology can achieve similar results against HIV infection.”

An mRNA vaccine works by delivering a piece of genetic material that teaches the immune system to recognize a target pathogen and mount a response, the NIH noted. The technology was used to create the first two licensed COVID-19 vaccines made by Pfizer-BioNTech and Moderna.

The new trial, HVTN 302, will assess whether three experimental HIV vaccines — currently named BG505 MD39.3 mRNA, BG505 MD39.3 gp151 mRNA and BG505 MD39.3 gp151 CD4KO mRNA — are safe and can induce immune responses.

The vaccines are designed to present the spike protein found on the surface of HIV. None can cause HIV infection.

HVTN 302 will be led by Jesse Clark, MD, an HIV researcher at the University of California, Los Angeles, and Sharon Riddler, MD, associate chief of clinical research at the University of Pittsburgh. It will enroll adults aged 18 to 55 years in 11 U.S. cities — Birmingham, Alabama; Boston; Los Angeles; New York; Philadelphia; Pittsburgh; Rochester, New York; and Seattle.

The researchers will randomly assign participants to one of six groups, each receiving three doses of one of the experimental vaccines. The first three groups, each made up of 18 participants, will receive intramuscular injections of 100 µg of their assigned candidate at their first visit and again at 2 months, followed by a third dose at 6 months.

Researchers will evaluate participants 2 weeks after their first dose to ensure that safety criteria are met. If so, the remaining three groups will be vaccinated with 250 µg of the assigned vaccine at the same time intervals.

The trial is expected to be completed by July 2023.

PERSPECTIVE

Paul A. Volberding

The amazing success of mRNA vaccines in COVID-19 makes it obvious and imperative to apply this technology to other viral infections that have been historic challenges to effective immunization development to date.

Certainly, HIV is high on this list.

The ability to tailor the immunogen so readily with the mRNA approach could allow the improved response we have waited for so long. This will be an interesting process to follow. Clearly, this is an understatement.

Paul A. Volberding, MD

Chief Medical Editor,Infectious Disease News

Professor emeritus of medicine

University of California, San Francisco

Safety, Activity, and Long-term Outcomes of Pomalidomide in the Treatment of Kaposi Sarcoma among Individuals with or without HIV Infection

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Abstract

Purpose:

Kaposi sarcoma (KS) is caused by Kaposi sarcoma herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8). KS, which develops most frequently among people with HIV, is generally treated with chemotherapy, but these drugs have acute and cumulative toxicities. We previously described initial results of a trial of pomalidomide, an oral immunomodulatory derivative of thalidomide, in patients with KS. Here, we present results on the full cohort and survival outcomes.

Patients and Methods:

Participants with KS with or without HIV were treated with pomalidomide 5 mg once daily for 21 days per 28-day cycle with aspirin 81 mg daily for thromboprophylaxis. Participants with HIV received antiretroviral therapy. Response was defined by modified version of the AIDS Clinical Trial Group KS criteria. We evaluated tumor responses (including participants who had a second course), adverse events, progression-free survival (PFS), and long-term outcomes.

Results:

Twenty-eight participants were enrolled. Eighteen (64%) were HIV positive and 21 (75%) had advanced (T1) disease. The overall response rate was 71%: 95% confidence interval (CI) 51%–87%. Twelve of 18 HIV-positive (67%; 95% CI, 41–87%) and 8 of 10 HIV-negative participants (80%; 95% CI, 44%–97%) had a response. Two of 4 participants who received a second course of pomalidomide had a partial response. The median PFS was 10.2 months (95% CI: 7.6–15.7 months). Grade 3 neutropenia was noted among 50% of participants. In the follow-up period, 3 participants with HIV had other KSHV-associated diseases.

Conclusions:

Pomalidomide is a safe and active chemotherapy-sparing agent for the treatment of KS among individuals with or without HIV.

Watch “Gravitas: 64-yr-old becomes first woman to be cured of HIV” on YouTube

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Mixed-race US woman becomes first to be cured of HIV using new cord blood treatment

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a coral in the dark

 A leukaemia patient in the US has become the first woman and the third person ever to be cured of HIV, after receiving a transplant of umbilical cord blood in a novel treatment technique, a New York Times report said Tuesday.

The previous two male patients who had been cured received expensive bone marrow transplants. Both kinds of transplants have stem cells with a mutation that blocks HIV.

The latest case was presented this week at the Conference on Retroviruses and Opportunistic Infections in Denver, Colorado.

The results show great promise in facilitating more accessible HIV treatments, especially for those who are already suffering from cancer. Cord blood is much more widely available than adult stem cells that are used in bone marrow transplants.

The middle-age woman is of mixed race and received a partial match, unlike the previous bone marrow transplants where a closer racial match is required and donors are primarily Caucasian.

Earlier, two other women had naturally cured themselves of HIV by locking away the virus in their genome in what is a ‘sterilising cure’, where the body eliminates the virus completely.

Cord blood treatment

The US mixed-race patient had been diagnosed with HIV in 2013 and had been on antiretroviral drugs. In March 2017, she was diagnosed with acute myelogenous leukaemia, and in August the same year, received the mutation-containing cord blood transplant.

She has not shown any signs of relapse since October 2020, when she received the transplant.

During and after the transplant, she also received blood for a close relative for temporary immunity, as cord blood cells can take up to six weeks to engraft. She was discharged 17 days after her transplant, and didn’t develop graft vs host disease, which was previously thought to be a step that contributed to the cure of HIV after bone marrow transplants.

Antiretroviral therapy, which typically is a drug cocktail that prevents replication and keeps viral levels low, was discontinued 37 months after the transplant, and 14 months since then, she continues to be in remission. Blood tests show no signs of both HIV and antibodies to HIV.

While the blood from her relative formed a crucial aid in keeping the immune system running until the cord blood cells took over, it is still unclear why cord cells were so effective.

However, the therapy itself is highly risky and only suitable for patients with cancer, as it destroys a large portion of the immune system using chemotherapy or radiation. 

Previous cures

In 2008, Timothy Ray Brown from California, who came to be known as the ‘Berlin Patient’, was the first to be cured of AIDS. His identity was revealed in 2010, and he died in 2020 from leukaemia.

Adam Castillejo, who was known as the ‘London Patient’, was the second to be cured, in 2019. 

Both men had painful and expensive bone marrow transplants from donors with a rare genetic mutation that is resistant to HIV. They were also on antiretroviral therapy.

Another patient, a 36-year-old man in Brazil, dubbed the Sao Paulo Patient, was temporarily able to remove the virus from his body using a drug cocktail and without surgery two years ago, but the virus rebounded with a detectable viral load 72 weeks or 15 months after he went off antiretroviral therapy.

Two women have been shown to be able to remove the disease naturally from their bodies. 

In 2020, scientists announced that 66-year old Loreen Willenberg from California was able to get rid of the disease by locking the virus away inside her genome, where it would typically replicate. Her body’s defensive action was described by researchers as a “functional cure”. She had been diagnosed with HIV in 1992.

Last year, a woman from Argentina, called the Esperanza patient, was also able to naturally remove the virus from her body completely in a “sterilising cure”. She had been diagnosed in 2013 and is now disease free. 

Such individuals whose bodies are able to suppress and lock away the virus, or eliminate it, are called elite controllers. It is thought that about 0.5 per cent of the 38 million HIV patients around the world make up elite controllers.

Young children have also been known to stay in remission when antiretroviral therapy is started at a very early age after birth.

Antimicrobial resistance killing more than HIV and malaria

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medication

A patient prepares to take his medication.

Speed read

  • Antibiotic-resistant infections led to more than 1.2 million deaths in 2019 – Lancet study
  • True picture could be much worse, with added impact of COVID-19, experts warn
  • Urgent policy measures needed in developing countries, say researchers

Antibiotic-resistant bacterial infections resulted in more than 1.2 million deaths worldwide in 2019, exceeding the number caused by HIV/AIDS and malaria, says a study spanning 204 countries and territories.

One in five of the deaths occurred in children under the age of five, with low- and middle-income countries bearing the highest burden, according to the analysis published in The Lancet, titled Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis.

The researchers say gaps in data in lower-income countries mean the full picture could be even worse, while other experts say the pandemic is also likely to have exacerbated the problem due to COVID-19 patients receiving antibiotics for secondary bacterial infections.

“Antimicrobial abuse has dramatically increased during the pandemic.”

Madhukar Pai, McGill University in Montreal, Canada

Antimicrobial resistance (AMR) is the development of resistance by various bacteria and other microbes against antimicrobial agents or antibiotics, including those used against common infections like lower respiratory tract and bloodstream infections.

The analysis in The Lancet points to an immediate need to scale up action on AMR and recommends urgent measures for policymakers, such as optimising existing antibiotic use, and improving infection monitoring and control.

“This is the most comprehensive study on the global burden of bacterial drug-resistant infections ever conducted,” said Christiane Dolecek, a co-author of the study and a professor who leads on global AMR research at Oxford University’s Centre for Tropical Medicine and Global Health and the Mahidol Oxford Tropical Medicine Research Unit.

“We hope that this report makes clear the impact now and future threat of this 21st century pandemic, and that it energises political leaders and the global community to implement the necessary measures to keep communities and patients safe and reduce this preventable burden,” she told Scidev.Net.

AMR’s global footprint

According to the study, AMR played a part in an estimated 4.95 million deaths and was directly responsible for an estimated 1.27 million deaths in 2019. This compares to 860,000 and 640,000 deaths respectively from HIV/AIDS and malaria in the same year.

Sub-Saharan Africa faced the highest burden, with 24 deaths per 100,000 people resulting directly from AMR, while the figure was 22 per 100,000 in South Asia. The number of AMR-linked deaths in those regions numbered 99 and 77 per 100,000, respectively.

The analysis also showed that of the 23 pathogens studied in the research, six bacteria – including Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae – directly caused the deaths of 929,000 people and were associated with 3.57 million deaths.

In Sub-Saharan Africa, deaths attributable to AMR mainly resulted from Streptococcus pneumoniae (16 per cent) or Klebsiella pneumoniae (20 per cent), while in high-income countries nearly 50 per cent of the deaths attributable to AMR were due to Escherichia coli (23 per cent) or Staphylococcus aureus (26 per cent).

Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security in the US, told Scidev.Net that antimicrobial resistance was one of the major public health threats of our time. “It threatens to pull us back to the pre-penicillin era,” he said.

To fight the scourge, says Dolecek, good vaccination coverage, especially of pneumococcal conjugate and flu vaccines, is needed, along with improved water and sanitation and better access to health services. “We need high quality, affordable and accessible simple rapid tests to reliably distinguish bacterial from viral infections on the spot in clinics,” she added.

Dolecek also recommended antibiotic stewardship initiatives to assess and improve how clinicians prescribe antibiotics and patients use them, and to curb inappropriate use.

According to the US Centers for Disease Control and Prevention (CDC), “improving antibiotic prescribing and use is critical to effectively treat infections, protect patients from harms caused by unnecessary antibiotic use, and combat antibiotic resistance.”

COVID-19 impact ‘not captured’

Madhukar Pai, Canada research chair in epidemiology and global health, and a professor at McGill University in Montreal, Canada, told SciDev.Net: “This is an important study that underscores the importance of antimicrobial resistance. But the impact of the COVID-19 pandemic is not captured.

“I hope it will be addressed in future updates of this study, because antimicrobial abuse has dramatically increased during the pandemic, with very high use of antimicrobial drugs such as azithromycin, doxycycline, ivermectin and hydroxychloroquine.”

COVID-19 patients admitted to hospital are often administered antibiotics to treat secondary infections, despite only a minority of cases having bacterial co-infections, according to a report in the BMJ.

“While these drugs are not effective for COVID-19, their widespread abuse makes me worried about antimicrobial resistance in the coming years,” added Pai.

The study says investment in the development pipeline for new antibiotics and access to second-line antibiotics where required are “essential” measures to counter this threat.

Diptendra Sarkar, a public health analyst and professor at the Institute of Post Graduate Medical Education and Research, in Kolkata, India, believes that irrational, non-evidence-based antibiotic use is responsible for the AMR crisis in developing countries.

“Immediate global action is necessary,” he told SciDev.Net. “All stakeholders, which include government regulatory authorities, medical professional bodies and the pharmaceutical industry, must initiate dialogues and draft a national, evidence-based, antibiotic policy.

Regulatory bodies in developing countries must prepare a roadmap for community and hospital infection audits, he said, adding: “Educating health care providers and strong surveillance is the way forward.”

Efficacy of a Two-Drug ART Regimen for Initial HIV Therapy

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In a pilot single-arm study, the two-drug regimen dolutegravir + lamivudine achieved viral suppression in 90% of patients at 24 weeks.

Increasing data support use of certain two-drug antiretroviral (ART) regimens for maintenance therapy for select HIV-infected patients suppressed on a standard ART regimen (NEJM JW Infect Dis Jan 2018). Experience with two-drug ART regimens for initial HIV therapy has been less favorable. In this pilot study, the two-drug regimen dolutegravir + lamivudine (3TC) was evaluated in treatment-naive HIV-infected patients without active hepatitis B infection who had HIV RNA levels ≥1000 and <500,000 copies/mL. The planned primary endpoint was the proportion with HIV RNA <50 copies/mL at week 24.

The study enrolled 120 persons at 26 sites in the U.S. (median HIV RNA, 4.6 log10 copies/mL; median CD4 count, 387 cells/mm3; 87% male; 72% nonwhite). At 24 weeks, 108 (90%) of the participants had HIV levels <50 copies/mL; results were similar for those with HIV RNA >100,000 or ≤ 100,000 copies/mL. Three participants met criteria for virologic failure; all had undetectable dolutegravir levels at ≥1 time points and one had M184V and R263R/K integrase mutations identified at time of failure. The regimen was well tolerated, with no treatment discontinuations due to adverse effects. The authors conclude that these results support further evaluation in select treatment-naive patients planned in the currently enrolling phase 3 studies.

Comment

Dolutegravir/3TC is a regimen of interest due to the potency and high barrier to resistance of dolutegravir and the potency, tolerability, and low cost of generic 3TC. Although these results are encouraging from the efficacy standpoint, the development of resistance to dolutegravir is worrisome and has not been generally observed with dolutegravir use as part of initial three-drug therapy. Results of the phase 3 GEMINI-1 and 2 trials comparing dolutegravir/3TC to a standard three-drug regimen for initial treatment (https://clinicaltrials.gov/ct2/show/results/NCT02831764), anticipated in 2018, will provide more definitive data on the potential of this two-drug regimen.

PrEP Isn’t Just for Men Who Have Sex With Men—Should You Be on It?

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Here’s what you need to know about the drug that prevents HIV.
Prep-Medication

You’ve probably heard of PrEP, maybe from a friend, an advertisement, or in health class. Regardless of how it came up, it was most likely referred to as something for men—specifically men who have sex with other men and want to avoid contracting HIV.

PrEP is a medication that can drastically lower someone’s risk of getting HIV. An estimated 120,000 people in the United States were taking it for that purpose at the start of 2017, according to a report from Gilead Sciences, PrEP’s manufacturer. But PrEP can help anyone at risk for HIV infection reduce that risk, no matter their gender or sexual orientation. Here’s what you need to know about HIV, how PrEP protects against it, and whether you should consider taking this drug.

First, here’s a primer on HIV and how it’s transmitted, which is essential in understanding why PrEP is so effective.

HIV, or human immunodeficiency virus, is spread through certain bodily fluids (blood, semen, pre-seminal fluid, vaginal and rectal fluids, and breast milk) from a person who has HIV, according to the CDC. It attacks the immune system by killing off a person’s T cells, aka CD4 cells, which help the body battle infection. If you don’t have enough of these cells, you’re more vulnerable to illnesses.

According to the most recent CDC data available, 1.1 million people in the United States had HIV in 2015. After peaking around 150,000 per year in the mid-1980s, the number of new HIV diagnoses gradually decreased and sat at 39,782 in 2016.

Men who have sex with men are at the highest risk of contracting HIV because receptive anal sex has the highest potential transmission rate of all types of exposure except blood transfusions. According to the CDC, the risk of contracting HIV through unprotected receptive anal sex with a person who has it is 138 per 10,000 exposures. This is because the delicate lining of the rectum is so thin that it can allow HIV to enter the body more easily.

For comparison’s sake, the chance of getting HIV from a blood transfusion from a person who has the virus is 9,250 per 10,000 exposures. The odds drop to 63 per 10,000 exposures for needle sharing during intravenous drug use, 11 per 10,000 exposures for insertive anal sex, 8 per 10,000 exposures for receptive penile-vaginal intercourse, and 4 per 10,000 exposures for insertive penile-vaginal intercourse. The risk from receiving or giving oral sex is “so low that it is not possible to put a precise number on it,” and the risk from things like biting and sharing sex toys is “negligible.”

Certain factors, like using condoms when possible and not letting a person ejaculate inside of you, can lower your risk. Others, like having other sexually transmitted infections, may raise it.

Contrary to a popular and damaging myth, HIV is not a death sentence.

A person infected with HIV who gets treatment early can live a happy, active life for nearly as long as a person without it, according to the CDC. This is because HIV medications can do an incredible job of preventing the disease from progressing into AIDS.

A person is diagnosed with AIDS, or acquired immunodeficiency syndrome, when HIV has attacked their system to the point where their CD4 count drops below 200 per cubic millimeter of blood, according to the CDC. This allows life-threatening “opportunistic infections” like pneumonia, tuberculosis, and various cancers, to wreak havoc on a person’s health.

HIV medications known as antiretroviral therapy (ART) can slow the progression of the disease and lower the chances of transmitting it to others. ART for people with HIV typically includes three medications from two different drug classes, according to the U.S. Department of Health and Human Services.

PrEP is the latest tool in the fight against HIV, and it works to prevent the infection from taking hold in the first place.

PrEP is a daily pill for HIV-negative people that, when taken consistently, can reduce the risk of HIV infection through sex by over 90 percent, according to the CDC. It can also lower the risk of HIV contraction in someone who injects drugs by over 70 percent when taken daily, according to the CDC.

PrEP comes as a pill under the brand name Truvada, which is actually a mix of the HIV medicines tenofovir and emtricitabine, and was first approved for use in the U.S. to prevent HIV in July 2012.

“These drugs were chosen because they have limited side effects, have few problems with drug resistance, and remain in the body for a relatively long time,” Mehri McKellar, M.D., an associate professor at Duke University’s Division of Infectious Diseases, tells SELF.

PrEP basically preloads your body with medicine, family doctor Adam Lake, M.D., an American Academy of HIV Medicine specialist working for Lancaster General Health in Lancaster, Pennsylvania, tells SELF. If exposure does occur, PrEP blocks pathways the HIV virus uses to infect your body. This prevents HIV from establishing itself so you can remain HIV negative.

It’s worth noting that PrEP is different from post-exposure prophylaxis (PEP), which can be taken within 72 hours after possible HIV exposure (like a sexual assault) and continued for the prescribed 28 days. When taken as directed, this antiretroviral treatment can stop the infection from taking hold in someone’s system. PrEP isn’t 100 percent effective in preventing HIV transmission, but the sooner it’s started, the better.

The problem is that some at-risk populations aren’t benefiting from PrEP as much as they could be.

Rates of new HIV diagnoses are highest for black and Hispanic/Latino gay and bisexual men, according to 2016 data from the CDC. Unfortunately, despite the fact that the majority of those living with HIV are people of color, 73 percent of people who filled PrEP prescriptions between January 2012 and September 2016 were white, according to Gilead Science’s 2017 report. “We need to make sure that African-Americans and Latinx are aware of PrEP and have access to this medication,” Dr. McKellar says.

And while the risk of HIV is highest among men who have sex with men, that doesn’t mean that other individuals (particularly those with other risk factors) can’t benefit from PrEP. That’s why Dr. Lake wishes more sex workers, intravenous drug users, and sexually active trans women knew about and had better access to PrEP, since their lifestyles put them at higher than average risk. So does being a cisgender woman or gender nonconforming person who’s had unprotected vaginal or anal sex with two or more partners in the last year, or who has a partner who has HIV or HIV risk factors.

If you’re concerned or meet certain risk factors, Dr. Lake suggests asking your doctor about PrEP. This doesn’t mean you definitely need to go on PrEP if you meet the qualifications. But it’s worth discussing with your doctor to see if your personal situation makes it a good choice for you, especially because you wouldn’t need to take it forever—only during periods of your life in which you’re at risk.

Of course, cost and side effects are both important considerations.

While PrEP’s cost varies depending on insurance, it can be prohibitively expensive, which is a hindrance to many people who need it. Without insurance, PrEP can cost up to $13,000 a year, according to the PrEP Facts, an awareness-raising project from the San Francisco AIDS Foundation and San Francisco Department of Health, among other groups.

There are, however, programs aimed at granting affordable access to those without insurance or those who need assistance paying their co-pays. If you have non-government insurance, you may be eligible for the Gilead Advancing Access program, which can offer up to $3,600 per year to help with co-pays based on your situation (you can learn more about the program’s terms here for the program’s full terms). If you don’t have insurance, are eligible for Medicaid, or your insurance denies your claim, the PrEP medication assistance program may help you get the drug for free. The CDC created a handy spreadsheet about paying for PrEP that you can check out, too. If all of this is confusing, you can ask your doctor if they have any information on how to lower the cost of PrEP or find an HIV-focused health center near you for more information.

Like any other medication, PrEP can have side effects. The most common ones are headache, abdominal pain, and weight loss, though in rarer cases it can cause kidney issues, liver and bone problems, and too much lactic acid buildup in your blood, which can be life-threatening. Make sure to discuss these risks thoroughly with your doctor before starting PrEP so you’re aware of any symptoms that are waving red flags.

Finally, the medication can only do its job well if you take it every day. It gets less effective if you don’t take it daily—commitment is key.

Even if PrEP isn’t right for you, it’s imperative that you know your HIV status, which is only possible through regular testing.

Regardless of your gender, orientation, or lifestyle, the CDC recommends that everyone between the ages of 13 and 64 get tested for HIV at least once. If you have certain risk factors like being sexually active, having been diagnosed with any sexually transmitted infections, and having had sex recently with someone whose history you don’t know, you should get tested at least once a year. The CDC also recommends that gay or bisexual men consider getting tested every three to six months.

There are various kinds of HIV tests available, including blood tests and oral swab tests. Some tests can give you results in 20 to 30 minutes, while other lab-based tests can take up to several days. Most forms of HIV testing can detect the virus in your body about 18 to 90 days after exposure, according to the CDC (so if you tested negative a few days after having unprotected sex, you should ask your doctor when to come in for another test). In general, tests that use blood from a vein can detect HIV sooner after infection than finger prick tests or oral swab tests.

The only way to know your and your partner’s HIV status is to get tested, and this is an especially necessary step to take if you’re considering not using condoms. Talking about HIV can feel scary, but let your partner know that you want to feel comfortable with them and getting tested will help quell your fears.

As a bonus, going in to get tested is the perfect time to ask your doctor whether you might be a good candidate for PrEP. If you think you’re at risk for contracting HIV—or are just curious about how well you’re protecting yourself, get tested and ask your doctor about what resources can help you have a healthier, safer sex life.

HIV’s Jump From Apes to Humans May Have Been Aided by an Unfortunate Deficiency

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Nobody knows quite when it happened. But some time in our not too distant past, a chimpanzee version of a pathogen known as simian immunodeficiency virus (SIVcpz) jumped species to infect humans.

Mutations in SIVcpz would turn it into the insidious human immunodeficiency virus (HIV-1) responsible for the global AIDS epidemic. New research suggests a common group of proteins should have protected us from infection, raising the question – how did it happen?

An international team led by researchers from the Heinrich-Heine-Universität Düsseldorf have investigated how a group of proteins called cellular cytidine deaminases (APOBEC3s or A3s in short) can offer humans protection from the virus that attacks apes.

Specifically, the scientists focussed on variants of a gene responsible for the cytidine deaminase APOBEC3H (A3H) and its role in the replication and possible transmission of the chimpanzee-specific virus.

The story of the rise of the HIV epidemic is murky up to the point when the first AIDS patients were reported in the US in the early 1980s.

While researchers can show a relationship with the simian version of the immunodeficiency virus, we can only speculate on how and when the virus leapt from apes to humans.

The transmission was more than likely passed through infected blood from meat, probably captured for food, and occurred far enough back in recent history for the virus to have had time to evolve into its current form.

Exactly why it happened at that moment – whether due to mutations or an unfortunate series of events – is still something of a mystery. But this new study could help shed some light on the question.

It’s known that the A3H cytidine deaminase proteins restrict the replication of the family of viruses both HIV and SIV belong to.

Usually these viruses can retaliate with a secret weapon of their own – a protective virulence factor called vif. But it doesn’t work as well against all versions of these anti-viral proteins.

What hasn’t been investigated until now is whether the human form of these proteins could have stopped the ape-infecting virus dead in its tracks in people.

To determine the extent of the proteins’ potential virus-busting powers, the researchers infected cultures of human kidney cells with easily-traced simian viruses from various sources. They also dosed the cells with genes to make either human or chimpanzee anti-viral proteins.

One particular human A3 protein called A3H haplotype II stood out from the crowd. It was particularly resistant to the virus’s vif, allowing it to sidestep the defence and rip into the SIV’s genes.

Turning to data from the Great Ape Genome Project, it was found that the chimpanzee version of A3H was less diverse than the human one.

What’s more, further experiments showed vif from chimpanzee and gorilla SIV could still interfere with chimpanzee A3H.

Taken together, it makes a compelling case for the hypothesis that humans evolved a solid defence against SIV.

That might go some way in explaining why in spite of living side by side with populations of great apes for so long, the leap of SIV to HIV was a significant recent event. But why did it happen at all?

Diversity can swing both ways. While humans clearly have evolved some remarkable versions of APOBEC that offer protection from SIVcpz, it’s likely that some individuals could lack that protection, or possess a weak or unstable version.

Scientists will be adding this puzzle piece to the collection, as future research continues to look at the relationship between cytidine deaminase and HIV – and it could help finally provide some answers.

CRISPR Gene Editing Has Been Used to Cure Mice of Sickle Cell Disease

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IN BRIEF
  • The results are promising and could lead to a treatment for this disease that afflicts about 100,000 Americans.
  • While human tests are still a ways off, CRISPR could one day be used to effectively treat a number of ailments, from high cholesterol to HIV.

CORRECTING A MUTATION

Gene editing shows promise as a new treatment for sickle cell disease, according to a study published in the online journal Science Translational Medicine.

Experts from the University of California, Berkeley, UCSF Benioff Children’s Hospital Oakland Research Institute (CHORI), and the University of Utah School of Medicine have found success in correcting the blood cell mutation in tests of the blood of both mice and human sickle cell patients using CRISPR-Cas9, a genome “scissor” that can cut out and edit a DNA sequence.

After CRISPR was used to correct the mutated hematopoietic stem cells — precursor cells that mature into the hook-shaped hemoglobin characteristic of sickle cell disease, the corrected blood stem cells produced healthy hemoglobin. Following reintroduction into the mice, the genetically engineered stem cells remained in circulation for at least four months — a significant indication that any potential therapy would be lasting.

 The tests of blood from afflicted humans showed that the proportion of corrected stem cells was high enough to produce substantial benefit for the patients, so the researchers are hoping to one day be able to reinfuse the human patients with the edited strain of cells as it could alleviate symptoms of sickle cell disease, including anemia and pain caused by vessel blockages.

While the results are promising and could lead to a treatment for this disease that afflicts about 100,000 Americans, the researchers emphasize that future testing on mice and safety analyses would need to be conducted before human trials could begin.

A CRISPR’D FUTURE

“Sickle cell disease is just one of many blood disorders caused by a single mutation in the genome,” said Jacob Corn, senior author on the study. “It’s very possible that other researchers and clinicians could use this type of gene editing to explore ways to cure a large number of diseases.”

Indeed, developments in gene-editing  technology within such fields as medicine, agriculture, and biology are taking us further into what some are calling “the age of CRISPR.”

It’s already being researched as a treatment for many other ailments and disorders— β-thalassemia, severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, even HIV — so this one type of technology could end up being something of a panacea for what ails us, as long as what ails us is genetic.