In the RADIANT-TB randomised controlled trial carried out in Khayelitsha, researchers found that tuberculosis (TB) patients with HIV taking a double dose of dolutegravir had similar viral suppression to those taking a single dose plus placebo. The findings, published in The Lancet HIV, suggest that a only once-daily dolutegravir is feasible in patients with HIV-associated tuberculosis.
WHO’s preferred first-line antiretroviral therapy (ART) regimen for adults and adolescents with HIV is dolutegravir, combined with tenofovir and lamivudine or emtricitabine. A disadvantage of dolutegravir is substantial drug–drug interaction with rifampicin, which is important as tuberculosis is the most common cause of hospitalisation and mortality among people living with HIV.
The drug–drug interaction between rifampicin and dolutegravir can be overcome by supplemental dolutegravir dosing, but is a challenge in resource-constrained settings. The researchers sought to investigate whether virological outcomes with standard-dose dolutegravir-based ART are acceptable in people with HIV on rifampicin-based antituberculosis therapy.
RADIANT-TB was a phase 2b, randomised, double-blind, non-comparative, placebo-controlled trial in Khayelitsha, Cape Town, South Africa. Participants were aged over 18 years, with plasma HIV-1 RNA >1000 copies/mL, CD4 count > 100 cells/μL, ART-naive or first-line ART interrupted, and on rifampicin-based antituberculosis therapy for less than three months. Participants were assigned (1:1) to receive either tenofovir disoproxil fumarate, lamivudine, and dolutegravir plus supplemental 50mg dolutegravir 12h later or the same drugs but with placebo in place of the supplemental dolutegravir. Participants received standard antituberculosis therapy (rifampicin, isoniazid, pyrazinamide, and ethambutol for the first two months followed by isoniazid and rifampicin for four months). The primary outcome was the proportion of participants with virological suppression (HIV-1 RNA <50 copies/mL) at week 24 analysed in the modified intention-to-treat population.
No treatment-related dolutegravir resistance emerged in the trial, and though not significant, an increase in insomnia was noted in the supplemental dolutegravir arm. In terms of future research, it is questionable whether a phase 3 trial would be needed given the significant time required for a policy change. Limitations included the study not being powered to compare efficacy.
The authors concluded, “Our findings suggest that twice-daily dolutegravir dosing might be unnecessary in people with HIV-associated tuberculosis. More evidence, from cohort studies or possibly a phase 3 trial, might be necessary to change policy on the need for a supplemental dolutegravir dose with rifampicin-based antituberculosis therapy.”
Both health minister Dr Joe Phaahla and health authorities in the Free State last week denied claims from activists that there are shortages of antiretroviral medicines at health facilities in the province. Authorities did however confirm that some people living with HIV are only given a two-week supply of medicines at a time.
“I can confidently say that there are no stockouts or shortages of ARVs in the Free State,” Phaahla told Spotlight at the World AIDS Day commemoration event in Mangaung.
This was reiterated by spokesperson for the Free State Department of Health, Mondli Mvambi saying, “We do not have shortages of HIV medicines in the province.”
He says allegations of patients not receiving their medication are very serious and cannot be taken lightly. He says should the department hear from patients who are not receiving their HIV medicine, they will investigate.
But Makhosazana Mkhatshwa, a research officer at the Treatment Action Campaign (TAC), says in the past three months, nine clinics in the province indicated that patients have left their facility without the medicine that they needed and of these nine clinics, three of them had sent people home because there was a stockout of HIV medication. She says impacted clinics include Poly Clinic and MUCPP in Mangaung, and Namahadi Clinic in Thabo Mofutsanyana District.
According to community-led monitoring group Ritshidze’s latest report on clinic services in the Free State, there were 40 patient reports this year of shortages of HIV medication compared to 13 patient reports last year. The report states that the most commonly reported medicine shortages by public healthcare users were contraceptives, HIV, and TB medicines. The report was based on monitoring at 28 clinics. TAC is a Ritshidze partner organisation.
Only 7 or 14-day supply for some
One woman Spotlight spoke to at the World AIDS Day commemoration event held in Mangaung last week says she is a patient at Pule Sefatsa Clinic in Botshabelo, Mangaung. “I am forced to go to clinic every week because they only give me a supply for eight days. This is an inconvenience for me because I have to skip work every week just to get my medication.”
Another public healthcare user from Bloemfontein tells Spotlight that for two weeks in October he was stranded without ARVs. He says that he is usually given a 14-day supply at a time. When he requested a full month’s supply to last him through a work-related trip to Cape Town he says his request was declined at the Poly Clinic at Pelenomi Hospital. He says he ended up going without medication.
Aron Malete, District Health Manager for Mangaung, told Spotlight there are no ARV shortages in the district, but asked for details of the above cases so that he could investigate.
The problem is not stockouts per se, but a shortage of medication, says Sello Mokhalipi, Secretary General of Positive Action Campaign. “You will find that there is a shortage of ARVs for seven days, then the next week it will be available,” he says.
Mokhalipi, like other activists Spotlight spoke to, is opposed to giving people only a seven or 14-day supply of medication at a time. He says people should be given enough for three to six months.
When Spotlight put the concerns and calls for multi-month dispensing to Mvambi he says, “We have identified people who are clinic hoppers who steal medicine. They get three months and thereafter run to another clinic to get another three months’ supply. To curb this practice,” Mvambi says, “we keep people on seven and 14 days’ supply The idea is to give them a few days because they claim to have forgotten their clinic cards.”
According to him, people get three months’ supply when they have their clinic card because clinic staff can verify who they are and what medicine they have been receiving.
Doing ‘exceptionally well’ but there are concerns
According to Phaahla who delivered a speech at the World AIDS Day commemoration event, the province has done “exceptionally well in terms of testing, having already surpassed the 94 percent threshold”. Phaahla said 94 percent of people who are living with HIV in the province know their status, 86 percent of those who know their status are on antiretroviral treatment, and 92 percent of those who are on treatment are virally suppressed.
He, however, singled out some districts such as Xhariep and Lejweleputswa where he says the “number of people with HIV and on treatment fare poorly on the target of being virally suppressed”. “This,” Phaahla says, “is very concerning and we must urgently intervene to create a balance among the targets in order to achieve zero new infections by 2030. This includes ensuring that services are brought closer to the people and that our health facilities are adequately resourced with medicine and related necessities.”
“Results for each of the sub-populations vary with adult females at 95 – 91 – 93, adult males at 93 – 77 – 93, and children at 82 – 65 – 68,” says Mvambi. “To achieve the 95 – 95 -95 targets the Free State must increase the number of adult men on ART by 25 745, adult women on ART by 9 744, and children on ART by 5 138.”
“As you can see,” says Mvambi, “the women are more likely to get tested, be initiated on ART, and have their viral load suppressed than their counterparts.”
According to the Free State Department of Health’s latest annual report for the financial year 2021/2022, the number of patients initiated on ARV treatment dropped from 36 776 in 2019/2020 to 26 364 in 2021/2022. In the report, the department states that it failed to meet its target for retaining adults on ART in care. The ART adult remain-in-care rate in 2019/20 was 68%. In 2020/21, it dropped to 52.8% and picked up in 2020/21 at 67.3%. Among the reasons the department cites are the high number of loss to follow-up of clients and “poor tracing by community healthcare workers due to poor supervision”.
NOTE: An employee of the TAC is quoted in this article. Spotlight is published by SECTION27 and the TAC, but is editorially independent – an independence that the editors guard jealously. Spotlight is a member of the South African Press Council.
The national Department of Health (DOH) has managed to secure a significant reduction in prices for antiretroviral medicines that treat HIV, with the price of the regimen that is prescribed to most new patients (tenofovir/lamivudine/dolutegravir – TLD) dropping over 30%, from R99 to R68. By comparison the regimen costs well over R250 in the private sector.
TLD is recommended by the World Health Organisation as the preferred first-line regimen for adults living with HIV.
Currently over 4 million South Africans are using this regimen, according to statistics from the DOH. There are about over 5.5 million people receiving treatment for HIV, and 8 million people living with the virus in this country.
Prices of ABC/3TC, commonly used to treat children with HIV, also fell with the DOH’s new contract.
Khadija Jamaloodien, director of the Affordable Medicines Directorate in the DOH, told GroundUp that South Africa is the biggest buyer of ARVs in the world. She said because of the sheer number of people needing ARVs, the department was able to bring the price down.
“Our volumes are just so huge that it makes it more efficient for manufacturers to be able to supply at reasonable prices,” said Jamaloodien.
She said another reason the department was able to reduce the price was that the manufacturers were applying for a three-year contract with “a certainty of demand”. She said constant communication with manufacturers about changes in demand also helped. If demand is likely to be reduced, the department would inform manufacturers who then would not “sit with stock that they are going to have to write off”.
The contract, which is already being executed, was awarded from July 2022 and ends in June 2025.
Jamaloodien said lower prices meant that the department could serve more patients and provide more medicines within the same budget envelope. (ARVs are provided free to public sector patients.)
Juliet Houghton, CEO of the Southern African HIV Clinicians Society (SAHCS), praised the DOH’s efforts to secure the ARVs so cheaply. She said a “healthy” degree of competition between manufacturers also helped drive prices down.
Houghton added that the reduction in prices “offers an opportunity to reinvest some of the savings into more expensive, particularly prevention drugs, that are coming”.
“As a country, we don’t want to just keep treating more and more people with HIV, we actually want to prevent it,” said Houghton. She said that the remaining budget could also be invested in prevention injectables, which might be more expensive.
Jamaloodien said that the injectable pre-exposure prophylaxis (PrEP) medicines are not yet registered with South African Health Products Regulatory Authority (SAHPRA). These help prevent sexually active people from contracting HIV. She said after the medicines are registered, they will have to look at whether they are affordable.
Francois Venter, executive director of Ezintsha at Wits, also praised the DOH’s “excellent work in securing these price reductions”.
“We also need the department to start using these processes better to secure similar world-class treatments for other common diseases – including diabetes, cancer, obesity, and TB,” he said.
The Treatment Action Campaign (TAC) has called on former president Thabo Mbeki to offer an apology to the public for the “dissident” views he expressed about HIV/AIDS while delivering a speech at the University of South Africa (UNISA) last week Wednesday.
In a scathing statement published by the TAC on Tuesday, the organisation said the “repetition of his scientifically erroneous views with such insensitive arrogance is an insult to the 8 million people living with HIV in SA and the families of 4 million South Africans who have died from HIV over the last three decades”.
Mbeki, who is also the Chancellor at UNISA, was speaking to students, diplomats and members of the media at an event which takes place twice each year and allows students to interact with him on pertinent issues that affect Africans.
The TAC accuses Mbeki of misleading the public when he questions the cause of AIDS. The organisation also goes on to say that they were stunned again by Mbeki’s support of the views of the late former Minister of Health, Manto Tshabalala-Msimang “who was ridiculed for promoting garlic and beetroot as the essential ingredient to manage AIDS, giving it a higher premium than antiretroviral (ARV) treatment”.
“Whilst there may be benefits in all healthy foods, the idea that these vegetables are what are most required in the management of AIDS has no basis in fact and is misleading to the public,” said the statement.
Speaking about HIV/AIDS after a question was raised in the event, Mbeki said the questions that he raised then, he would still raise today. He emphasized that AIDS was a syndrome and not a disease.
“Now this syndrome in medical terms is a group of diseases. So all of these diseases which fall under this syndrome, meningitis, TB, they’re in the syndrome.”
“Causes of Tuberculosis are known and historical, but it’s part of the syndrome. So you can’t say one virus causes all of these illnesses, what you can say is this virus impacts negatively on the immune system, it’s that weakened immune system which results in a syndrome.”
“But there’s a consequence to that kind of thinking which is when you go to test and that test says HIV positive… it does not necessarily mean you’ve got the virus. What it means is that the immune system is responding to something that is threatening the body, and therefore you need a clinical analysis in order to determine what is this thing that the immune system is rejecting. It’s in all the medical documents that go about it, and it’s correct, because then you have to go and do this clinical examination in order to determine which of these illnesses in the syndrome is the one that’s affecting this person. And then you treat the person for that particular disease,” said Mbeki.
Mentioning the views of Tshabalala-Msimang, Mbeki started off by saying as government they had to respond in an effective manner to the HIV/AIDS pandemic and various interventions were needed to do this.
“Which is why the question was raised by the then Minister of Health in a very dramatic fashion. Nutrition. Nutrition is very very critical to solving this problem and that’s why she was saying that we must take garlic and beetroot and so on. She was not saying that with those things you’re going to be cured.”
“She was raising the matter about the importance of nutrition. And those particular types of foods even today have been raised in the context of this Covid-19,” said Mbeki.
The TAC, which successfully campaigned in the 2000s for Mbeki’s government to roll out life-saving medicines, was not impressed.
“There is much ongoing stigma and denial when it comes to HIV and we call on Mr Mbeki to desist from statements about HIV that have no basis in fact,” said the TAC statement.
It said: “The former president’s statements remind us that his unscientific views led to a delay in the rollout of the ARV programme during his presidency.”
The TAC’s General Secretary, Anele Yawa, said that if Mbeki was not prepared to apologise, the organisation would make sure that his HIV denialism and the thousands of deaths that resulted, would be the only thing that he would be remembered for.
These are the facts when it comes to HIV/AIDS under Thabo Mbeki’s presidency
By Nathan Geffen, GroundUp Editor
It’s seldom clear what Thabo Mbeki means when it comes to HIV/AIDS. There is much obfuscation. But the key facts are this:
HIV destroys immune system cells in infected people.
Usually over a period of several years, if left untreated, the immune system collapses, causing the person to become ill with life-threatening infections. This is known as AIDS.
Only antiretroviral medicines can halt this process. They have been so effective that the life-expectancy for people with HIV who take them is brought back to almost normal.
HIV tests are reliable. If proper protocols are followed the odds of an incorrect result are extremely small.
Mbeki’s government delayed the rollout of antiretroviral treatment in the public sector until 2004, even though an effective combination of antiretroviral medicines was available from the mid to late 1990s.
It was only due to pressure from the TAC and its allies that Mbeki’s government made antiretrovirals available in the public sector.
The prices of these medicines also became affordable because of the TAC’s (and its allies) campaigning against pharmaceutical companies. Mbeki’s government was largely AWOL in these efforts, despite Mbeki’s rhetoric about these companies.
Two different studies have estimated that the delayed rollout of antiretrovirals resulted in well over 300 000 avoidable deaths. These estimates are conservative.
These estimates also exclude those who died because they were convinced by Mbeki, Tshabalala-Msimang and their acolytes to try treatments promoted by as alternatives to antiretroviral medicines. The promotion of these nonsense remedies by Mbeki and his health minister continued long after the antiretroviral treatment rollout began.
Geffen was involved with the TAC from 2000 to 2013.
Dolutegravir-based antiretroviral therapies (ART) for HIV-1 are more effective for pregnant individuals than some other ART regimens commonly used in the US and Europe, according to a study available online in NEJM.
The study, led by Harvard T.H. Chan School of Public Health researchers, showed that pregnant individuals who took dolutegravir-based regimens had a high probability of being virally suppressed at delivery. No differences were seen in adverse birth outcome risks (preterm birth, low birth weight, small for gestational age, or neonatal death) between dolutegravir-based regimens and the other contemporary regimens.
“Globally, a dolutegravir-based regimen is currently recommended for treating HIV, and this is the first study to directly compare regimens including dolutegravir to other antiretroviral regimens, such as raltegravir-based regimens, that are also listed as ‘Preferred’ in US perinatal guidelines,” said senior research scientistKunjal Patel, lead author of the study.
Dolutegravir, is a newer antiretroviral part of a once-a-day regimen that has been shown to be more effective, easier to tolerate, and less likely to create new drug resistance in people with HIV-1. However, limited data have been available about its effectiveness and safety in pregnancy compared with regimens that commonly have been used during pregnancy in the US and Europe.
In the current observational study, the researchers compared dolutegravir use in pregnancy with atazanavir/ritonavir, darunavir/ritonavir, and raltegravir antiviral regimens that are currently classified as “Preferred” for use in pregnancy in the US About half of the participants started ART before conception. At delivery, 96.7% of pregnancies of participants who received dolutegravir were virally suppressed, whereas those of participants who took atazanavir/ritonavir or raltegravir had viral suppression of 84.0% and 89.2%, respectively.
“We think the observed differences are due to dolutegravir’s ability to rapidly decrease viral loads and its ease of use as part of a once-daily regimen that’s available as a fixed-dose combination,” said Patel. “Our results highlight the continual need for systematic studies that compare new antiretroviral regimens with those already in clinical practice to help inform the evolution of guidelines and clinical practice over time.”
Specifically designed cocktails of broadly neutralising antibodies (bNAbs) could help treat HIV while minimising the risk of the virus escaping treatment, researchers reported in eLife.
The study shows that computational approaches to selecting combinations of bNAbs based on viral genetics could help prevent viral escape, making HIV treatment more effective. It may also offer a strategy for designing effective combinations of bNAbs for treating other rapidly evolving pathogens.
bNAbs offer a promising new tool to treat or potentially cure infections with rapidly evolving viruses such as HIV. Clinical trials using a single bNAb to treat HIV have shown that some viral strains may survive the treatment and lead to a rebound of viruses in the blood. Combinations of bNAbs may therefore be a more effective approach, but finding the best combinations is a challenge.
“For our study, we proposed using a computational approach to predict the effectiveness of bNAb combinations based on the HIV genetics,” said researcher Colin LaMont.
LaMont and colleagues analysed the genetics of HIV viruses collected over 10 years from 11 untreated patients with HIV, and used this data to predict which viral strains might be able to escape treatment with different bNAbs and whether dodging bNAbs had a survival cost. Next, using computational methods, they applied the knowledge gained to predict viral rebounds in three real-life trials of bNAbs.
Finally, the team used their computational approach to find a combination of bNAbs that is least likely to allow any virus to escape. They also found that some bNAbs, such as 10-1074, are better against diverse populations of viruses because mutations that allow viruses to escape also make the virus less likely to survive. Others, including PGT121, are more effective against less diverse viral populations because mutations that enable escape are rare. Overall, the results suggested that the optimal combination includes three bNAbs: PG9, PGT151 and VRC01.
“We’ve shown the combination of PG9, PGT151 and VRC01 reduces the chance of viral rebound to less than 1%,” LaMont said. “It does this by targeting three different regions of the virus’ protective outer wrapping, or envelope.”
“Combining bNAbs, administered via intravenous infusion every few months, with current antiretroviral therapies (ART) that require daily doses could further improve long-term HIV treatment success,” suggested senior author Armita Nourmohammad, Assistant Professor at the University of Washington.
ART hinders HIV multiplication and ability to create new variants, limiting the genetic diversity of the viral population and reducing the odds of bNAb escape variants emerging. The authors say that more studies are needed to confirm the potential benefits of combining ART and bNAbs.
“Our study shows that leveraging genetic data can help us design more effective HIV therapies,” Asst Prof Nourmohammad concluded. “Our approach may also be useful for designing therapies against other rapidly evolving agents that cause disease, such as the Hepatitis C virus, drug-resistant bacteria, or cancer tumour cells.”
The South African HIV Clinicians Society (SAHCS) have recently announced a clinical update on the dolutegravir (DGT)-based regimens for first- and second-line antiretroviral therapy. This comes in the wake of positive findings from a number of clinical trials.
“Based on data from several recent trials, we now recommend that all patients > 10 years old and 35 kg on tenofovir/emtricitabine (or lamivudine)/efavirenz (TEE/TLE) or NVP-based regimens be switched to tenofovir/lamivudine/dolutegravir (TLD) regardless of the viral load (VL) result. In addition, all patients > 10 years old and > 35 kg on a regimen of two nucleoside reverse transcriptase inhibitors (NRTI) with a boosted protease inhibitor (PI) (eg, lopinavir/ritonavir (LPV/r) or atazanavir/ritonavir (ATV/r)) and a suppressed VL can be switched to TLD, regardless of prior resistance patterns or treatment history.”
In South Africa, pre-treatment resistance to nonnucleoside reverse transcriptase inhibitors (NNRTI)-based antiretroviral therapy regimens has been rising. Meanwhile, DTG has a higher barrier to resistance and reduced side effects. This prompted the Department of Health to recommend that patients on NNRTI-based ART regimens be switched to DTG-based regimens. This transition is slower than desired partly because a documented suppressed VL is required prior to switching from TEE/TLE to TLD. Since this recommendation was first made, evidence from several trials (NADIA, VISEND and ARTIST) has demonstrated that tenofovir with lamivudine can be safely and effectively recycled from a first- to a second-line regimen. Therefore, the SAHCS has stated that “in patients with virological failure on a TEE or TLE regimen a single drug can be switched (efavirenz to dolutegravir ie, TLD as secondline), resulting in virological suppression comparable to or better than alternative second-line options.”
The guidelines also outline the results of the NADIA, VISEND and ARTIST trials conducted in southern African countries, as well as the single-arm DAWNING trial.
Kaposi sarcoma on the skin of an AIDS patient. Credit: National Cancer Institute
A study published in Cell Reportshas identified a protein in the cancer cell’s nucleus as a critical agent keeping Kaposi sarcoma-associated herpesvirus (KSHV) dormant and hidden from the immune system. The virus, in the same family as Epstein-Barr virus, is linked to AIDS-related Castleman’s disease and cancers such as Kaposi sarcoma.
Up to 50% of the population in some parts of Africa are affected with KSHV, though not everyone with KSHV will develop Kaposi sarcoma. Those who do typically have a weakened immune system due to HIV infection, organ transplant, being older or other factors.
The introduction of antiretroviral therapy significantly reduced AIDS-related Kaposi sarcoma prevalence in Western countries; however, in sub-Saharan Africa, the disease continues to have a poor prognosis.
On entry into a human cell the virus causes a hidden infection in the nucleus: the virus simply latches onto parts of the cell’s chromosomes without replicating.
Researchers studied KSHV’s latent-lytic switch, a process in which the virus exits its dormancy state to replicate in the host cell. This replication phase, called the lytic cycle, ends with the disintegration of the cell and the release of the viruses, infecting neighbouring cells.
“The virus likes to stay silent as long as possible to avoid being detected by the body’s immune system,” said Professor Yoshihiro Izumiya, the study’s senior author.
The team sought to understand the mechanisms behind this latent-lytic switch and the role the host cell environment played in this process.
“Where the virus latches onto the host cell, how it manages to stay dormant, and what triggers its activation were very exciting and important puzzles to solve,” Prof Izumiya said.
The study identified where the virus genome could be found on the host genome.
Izumiya and his team profiled and analysed chromosomal interactions on three cancer cell lines naturally infected with KSHV, locating the virus’s preferred chromosome docking sites. The binding patterns, similar among the three cancer cell lines, showed a nuclear ecosystem that can attract and help keep the virus in its silent form.
The team also found that CHD4 (chromodomain helicase DNA binding protein 4) binds to the virus’s genomic elements. CHD4, a protein in the host cell’s chromosomes, suppresses the work of the gene responsible for viral replication. The study showed that CHD4 is a key regulator of the KSHV latency-lytic switch.
“The location where the virus genome attaches to the host chromosome is not random,” said Ashish Kumar, a postdoctoral researcher in Izumiya Lab and the paper’s first author. “Without having enriched CHD4 protein, the virus starts to replicate, kicking in a cell destructive mode. For the virus to select CHD4 among many other host proteins, CHD4 must play a unique and important role in host cells.”
Virology can help identify cellular proteins essential for cell homeostasis. Over millions of years, the virus’s genome developed to encode or assemble a small number of very efficient proteins, which strategically connect to host cell proteins to keep viral chromatin dormant and impact the host cell’s tumour suppression function.
“We used virology as an entry point to shed light on the function of CHD4 in gene regulation in general. During virus-host co-evolution, KSHV cleverly learned to hijack host proteins that can help keep the gene responsible for viral replication dormant.”
The researchers found a viral protein which could serve as the basis for a replication inhibitor. Since CHD4 is critical for cancer cell growth in a variety of cancers, they hope this virus-host interaction could inform cancer treatment research.
A trial has successfully used a novel treatment of anti-HIV antibodies to achieve viral suppression in several HIV patients. The results published in Nature, would enable a treatment not reliant on vigilant daily dosing and which could potentially reduce the body’s reservoir of HIV, something antiretroviral drugs cannot do. The antibody treatment could be used in combination with long-acting antiretrovirals, or alone after such medications have sufficiently brought down viral levels.
“The idea is that you would still be on HIV treatment, but instead of having to take a pill every day, with the long-acting versions of the antibodies, patients would be able to take infusions every six months,” said Professor Marina Caskey, who co-led the study.
In this trial, 18 participants received seven infusions of a pair of broadly neutralising antibodies over five months, while discontinuing their antiretroviral medications. Thirteen of these participants maintained viral suppression for at least five months, and in a few cases over a year, suggesting the antibodies are able to control viruses that are sensitive to the antibodies and prevent viral levels from rising to dangerous levels.
Besides suppressing the virus, antibody therapy may also have an effect on cells infected with HIV that cannot be eliminated by antiretroviral drugs. “Ultimately, with any treatment, we’d like to see a decline in the reservoir of infected T-cells, which fuel rebound when therapy is discontinued,” says Christian Gaebler, an assistant professor of clinical investigation in Nussenzweig’s lab and the study’s first author. After therapy, the team detected a decrease in the infected T-cells, specifically those that harbor intact viruses capable of replication. “It’s a promising finding that we hope to follow up on in future, larger studies,” Gaebler says.
The new study built on a previous, shorter trial in which participants had received three antibody infusions over six weeks. The researchers found that administering additional infusions was generally safe and well-tolerated, and the longer treatment period did not result in the emergence of new resistant variants.
Even with antiretroviral therapy, HIV still lingers in the body, preventing complete cure. Now, new research published in PLOS Pathogens, revealed a possible answer to why HIV persists in the body: a lack of a certain protein in HIV patients’ killer T cells. The discovery also explained why people with HIV have less risk of developing multiple sclerosis (MS).
Because this protein, CD73 is responsible for migration and cell movement into the tissue, the lack of the protein compromises the ability of killer T cells to find and eliminate HIV-infected cells, explained immunologist Shokrollah Elahi, lead researcher of the study.
“This mechanism explains one potential reason for why HIV stays in human tissues forever,” he said, adding that the research also shows the complexity of HIV infection.
“This provides us the opportunity to come up with potential new treatments that would help killer T cells migrate better to gain access to the infected cells in different tissues.”
After spending three years identifying the role of CD73, Elahi turned his focus to understanding potential causes for the drastic reduction. He found it is partly due to the chronic inflammation that is common among people living with HIV.
“Following extensive studies, we discovered that chronic inflammation results in increased levels of a type of RNA found in cells and in blood, called microRNAs,” he explained. “These are very small types of RNA that can bind to messenger RNAs to block them from making CD73 protein. We found this was causing the CD73 gene to be suppressed.”
This discovery also helps explain why people with HIV have a lower risk of developing MS, Elahi noted.
“Our findings suggest that reduced or eliminated CD73 can be beneficial in HIV-infected individuals to protect them against MS. Therefore, targeting CD73 could be a novel potential therapeutic marker for MS patients.”
Elahi said the research could next look into seeing how to turn on the CD73 gene in patients with HIV and off in those with MS.
