A Personal Reflection on World AIDS Day 2025
As I reflect on World AIDS Day 2025, I find myself thinking about the early days of my career in Durban, South Africa. Standing in clinics and research labs, I’ve witnessed both the triumphs and challenges of the HIV/AIDS response. Antiretroviral therapy (ART) has transformed HIV from a death sentence into a manageable condition for millions. Yet I’ve also met people for whom daily ART is a struggle – due to side effects, adherence difficulties, limited access, or persistent stigma. These experiences kindled a personal resolve: to seek innovative solutions that might one day offer long-term viral control without the need for daily medication. A curative or long-term control strategy without continuous pills would be a game-changer for pandemic management. This conviction set me on a scientific journey exploring broadly neutralizing antibodies (bNAbs) – specialized antibodies capable of targeting HIV. Little did I know that this path would lead to a comprehensive review article and a deeper appreciation of how far we’ve come.
Our recently published review, “Clinical trials of broadly neutralizing monoclonal antibodies in people living with HIV – a review” (AIDS Research and Therapy, 2025), emerged from this journey. Writing that paper was both an intellectual adventure and a personal mission. It allowed my colleagues and me to piece together the story of bNAbs in HIV therapy: from early passive immunotherapy experiments decades ago to the cutting-edge trials of today. In the spirit of a Springer Nature “Behind the Paper” narrative, I’d like to share the story behind our review – a story of scientific curiosity, collaboration, and hope – and how it aligns with the themes of innovation, long-term control, and inclusion on this World AIDS Day.
Rediscovering an Old Idea – and Pushing It Forward
In the 1980s and 90s, long before I entered the field, researchers had a bold idea: could giving HIV-positive people antibodies from others help control the virus? Early clinical experiments infused patients with plasma or first-generation monoclonal antibodies. The results were modest – hints of reduced viral levels and slightly fewer infections – but not the breakthrough they hoped for. The virus would invariably bounce back, finding ways to escape the antibodies. These attempts taught us an important lesson: HIV’s diversity meant that a single antibody was like a lone guard trying to stop an army; the virus could simply find another route. By the 2000s, three particular antibodies (2G12, 2F5, 4E10) were tested in people. They were safe and well-tolerated but using them in combination still did not prevent viral rebound when ART was paused. The virus quickly developed escape mutations, underlining the need for stronger defenses.
As a young researcher, I learned about these historical trials and why they fell short. However, rather than seeing it as a failure, I saw a foundation. The concept of passive immunotherapy – delivering antibodies to treat disease – was valid; we simply needed better antibodies. Fast forward to the 2010s, when technological breakthroughs changed the game. Scientists discovered that a small fraction of people living with HIV – often called “elite neutralizers” – naturally produce exceptional antibodies after years of infection. By isolating B-cells from these individuals, researchers uncovered a new generation of bNAbs with remarkable breadth and potency. These antibodies could neutralize a wide range of HIV strains by targeting conserved epitopes on the virus’s envelope – regions that HIV finds hard to change without compromising its own survival. Suddenly, we had names like VRC01, 3BNC117, 10-1074, and others entering the lexicon of HIV research. They went after critical sites on the HIV-1 envelope spike: the CD4 binding site, the V2 loop apex, the V3-glycan region, the gp120–gp41 interface, the MPER on the viral surface, even a patch called the “silent face” that normally hides from immune attack.
With these new tools in hand, the field moved quickly into clinical trials. I vividly remember the excitement in 2015 when early studies of VRC01 (one of the first broadly neutralizing antibodies isolated by the NIH Vaccine Research Center) reported that a single infusion could modestly lower the viral load in people with HIV. Could this really work in humans? Over the next several years, multiple trials were launched globally – including in the United States, Europe, and here in South Africa. When my colleagues and I set out to review this burgeoning field, we identified 154 registered trials, ultimately analyzing data from 62 trials focusing on people living with HIV (excluding prevention-only studies) to see the big picture of what bNAbs have achieved.
The story that emerged from our review was fascinating. Early single-antibody trials confirmed that bNAbs are generally safe and well-tolerated – an encouraging starting point. In fact, across intravenous, subcutaneous, and intramuscular administrations, most side effects were mild and transient (like low-grade chills or injection-site soreness). This favorable safety profile is likely due to bNAbs’ high specificity for HIV, meaning they don’t cause widespread collateral damage in the body. For me as a clinician, knowing that a new therapy is safe is crucial – especially if we envision offering it to otherwise healthy individuals to maintain long-term control of the virus.
Safety alone, of course, isn’t enough. The real question was: can these antibodies reduce the virus in the bloodstream, and for how long? The first trials showed transient and limited viral suppression – bNAbs could knock the virus down but not keep it down for long. For example, a person given 3BNC117 might see their virus drop significantly – often a 10-fold or even 300-fold decrease in viral load for a few weeks – but as soon as the antibody levels waned, the virus returned. Why? HIV had escaped by selecting for mutant strains that the given bNAb couldn’t neutralize. I found it both sobering and awe-inspiring that the virus could adapt so swiftly. In one early trial, 8 of 13 participants developed resistance to 3BNC117 after a short period. This highlighted a core challenge we kept revisiting while writing the review: viral resistance is the Achilles’ heel of bNAb monotherapy.
The logical next step – and one of the key insights from our review – was that using combinations of bNAbs could substantially delay or prevent this viral escape. Just as effective HIV drug regimens use 3+ drugs, antibody therapy may need multiple bNAbs targeting different parts of the virus. Excitingly, researchers tested this idea in clinical studies. One combination, 3BNC117 + 10-1074, showed that in individuals whose viruses were sensitive to both antibodies, the virus could be suppressed for 15 weeks, 30 weeks, or even longer without any ART. In these participants, the virus did not find a way around both bNAbs simultaneously, and no new resistance mutations emerged during the period of antibody coverage. Reading these results make you ponder – this was a proof of concept that dual bNAb therapy can achieve a couple of months of control, something previously seen only with daily ART. However, even this dual strategy wasn’t foolproof. In some individuals with pre-existing resistance to one of the pair, the benefit was blunted. This emphasized another lesson: baseline viral testing might be important to customize which bNAbs to give to a person (to ensure the virus isn’t already resistant from the start).
Key Findings – Hope and Challenges in Equal Measure
Analyzing all these trials for our review felt like assembling a complex puzzle. We saw consistent themes of promise coupled with persisting challenges. On the promising side, bNAbs clearly work antivirally – they can neutralize the virus and even enlist the immune system to attack infected cells. Unlike ART, which only blocks new viral replication, bNAbs have a dual action: they bind and neutralize free-floating virus, and they tag virus-infected cells for destruction by immune cells (through processes like antibody-dependent cellular cytotoxicity). In some studies, giving bNAbs to people about to interrupt their ART appeared to boost their HIV-specific CD8 T-cell responses. In other words, the antibodies might be awakening the body’s own killer T-cells to help control HIV – a fascinating bonus effect that blurs the line between treatment and vaccine. It’s still unclear if these immune boosts are directly causing the extended virus control seen, but it suggests that bNAbs could rally the immune system in ways ART does not. As a researcher, this potential immune synergy is thrilling: it means bNAbs aren’t just passive drugs, they are more like partners working with the patient’s immune system.
Another key insight from our review was the importance of second-generation bNAbs – those with enhanced potency or engineered for longer half-life – and how they perform in the clinic. Antibodies like VRC07-523LS (a modified antibody that stays in the body longer) and CAP256V2LS (an antibody derived from a South African donor, engineered for durability) are entering trials. By extending antibody half-life, we could move from needing infusions every few weeks to perhaps every few months, making therapy far more practical. In one trial, the long-acting versions of 3BNC117 and 10-1074 (given alongside the fantastic long-acting HIV drug called lenacapavir) managed to keep the virus suppressed for at least 26 weeks in most participants who stopped standard ART. Think about that – six months of freedom from daily pills, using just two antibody infusions and an injection of a novel drug. Similarly, an ambitious trial in the United States and sub-Saharan Africa tested a triple combination of bNAbs (PGT121, PGDM1400, and VRC07-523LS). When these three were given together to people who had their regular ART paused, the results were unprecedented: 10 of 12 individuals maintained undetectable viral loads for at least 28 weeks, and about half of them had no rebound for almost 9 months. Some of these participants stayed suppressed even after the antibodies faded from their blood, hinting that something beyond just the drugs was at play – perhaps an improved immune response or a reduced reservoir of latent virus. For context, without any intervention, most people would see HIV come back within 2–4 weeks of stopping ART. So a delay of 28, 36, even 44 weeks is remarkable. It inches us closer to what we call a functional cure – controlling HIV without daily treatment.
Of course, our review also underscored the stark challenges that remain. Viral resistance is the most obvious: HIV’s ability to mutate means bNAbs (especially if used one at a time) can be outmaneuvered. We saw this in trial after trial. Even with combinations, there is a cat-and-mouse dynamic – you might corner the virus for a while, but any gap in coverage can let an escape mutant flourish. This is why many scientists believe cocktails of 3 or more bNAbs (or multi-specific engineered antibodies) will be needed for a durable effect in most people. Another challenge is the latent reservoir of HIV – the sleeper cells harboring virus that even the best bNAbs can’t directly neutralize if the virus isn’t actively produced. bNAbs by themselves don’t eradicate these hidden viruses. Some trials attempted a “shock and kill” strategy: using latency-reversing agents (LRAs) to wake up latent HIV (the “shock”), then relying on bNAbs and the immune system to kill those cells. In theory, this could shrink the reservoir. In practice, results so far have been mixed. One study we reviewed gave participants the drug romidepsin (an LRA) along with 3BNC117 – but it did not significantly delay viral rebound or reduce the reservoir compared to controls. On the other hand, another study (eCLEAR trial) suggested that 3BNC117 (with or without an LRA) accelerated the clearance of infected cells and led to a lower reservoir and stronger T-cell immunity than ART alone. These early attempts teach us that while bNAbs have a role in HIV cure research, they likely need to be part of a multi-pronged attack – perhaps combined with vaccines, LRAs, gene therapies, or other immune modulators – to tackle the resilient latent reservoir.
Towards Long-Term Control and Inclusion: The Road Ahead
By the time we concluded writing the review, I felt a profound sense of both optimism and responsibility. The optimism comes from the clear message that bNAbs can work – they can safely suppress HIV, prolong the time off therapy, and possibly engage the immune system in fighting the virus. This is a major paradigm shift in HIV treatment research. We are no longer limited to small-molecule drugs; we have a whole new class of biological therapy to deploy. The responsibility, however, comes from recognizing what it will take to translate this progress into real-world impact. Chief among these is the need for affordable, scalable solutions. Monoclonal antibodies are expensive to produce – far more costly than typical antiretroviral pills. As our review noted, high production costs and scalability issues are a significant hurdle to making bNAbs part of routine HIV care. Manufacturing advances (like using engineered cell lines or even plants to produce antibodies) and increased investment will be required to drive down costs. We highlighted in the paper that developing more cost-effective bNAbs is crucial for sustainable HIV treatment. On World AIDS Day, this resonates strongly with the theme of inclusion. We cannot afford for bNAbs to become a luxury treatment available only in high-income settings. The communities hit hardest by HIV – many in sub-Saharan Africa, including my own country – must equally benefit from these innovations. This means planning now for equitable access: conducting trials in diverse populations, understanding how bNAb therapy performs in different contexts (for instance, in people with tuberculosis or other co-infections common here), and building manufacturing and delivery infrastructure that low-resource health systems can support.
Another aspect of inclusion is recognizing that not everyone living with HIV has the same needs. Who might benefit most from bNAbs? Our review suggests a few scenarios. For one, individuals who cannot tolerate or adhere to daily ART might find periodic antibody infusions or injections more manageable. I think of some of my patients who, for various reasons – whether it’s pill fatigue, mental health, or social circumstances – struggle with daily regimens. A therapy given perhaps every 3–6 months could be life-changing for them. Additionally, people with drug-resistant HIV could use bNAbs as an alternate route to control the virus, since bNAbs target the virus’s outer envelope (which is unrelated to typical drug resistance mechanisms). There is also interest in using bNAbs in specific situations, like during the postpartum period for women who had HIV during pregnancy, or in controlled interruptions of ART under medical supervision, to see if immune control can be achieved. These use-cases underscore the idea that bNAbs might fill gaps that current ART leaves open, making the overall HIV treatment toolkit more inclusive of different patient circumstances.
From a long-term control perspective, one of the most profound implications of bNAb research is its alignment with the vision of durable remission. We now talk about the possibility that some people, through a combination of therapies, might achieve remission – staying off all treatment for extended periods without viral rebound. It’s a concept inspired by the few documented cases of HIV cures (e.g. the “Berlin patient” and others who received stem cell transplants) but aiming for something far more scalable and safe than a transplant. bNAbs have moved us closer to that vision. They may not be the cure on their own, but our review makes it clear they could be part of the cure strategy toolkit. In fact, bNAbs are already being used in clinical trials together with vaccines (to train the body to make similar antibodies) and with other long-acting antivirals. The path to ending the HIV epidemic will likely involve integrating these antibody-based approaches to achieve what we call functional cure or long-term viral suppression without daily meds.
Working on this review also reinforced for me the importance of clinical partnerships in Africa. All too often, cutting-edge therapies take years to reach the Global South, if they arrive at all. I’m proud that in the bNAb field, African scientists and trial participants have been actively involved from the beginning. Our team itself was a collaboration across South Africa – spanning Durban, Cape Town, Johannesburg – and international partners. We acknowledged, for instance, the contribution of CAPRISA 012 and CAPRISA 095 (the NeutART study), trials taking place in South Africa that are evaluating bNAbs in our local context. Such partnerships ensure that we ask research questions that matter on the ground here (like how to effectively deliver these treatments in our healthcare settings) and that we build capacity locally for advanced therapies. On this World AIDS Day, I feel encouraged that global initiatives are increasingly supporting Africa-led innovation – from funders investing in antibody production to training programs for young researchers. This collaborative spirit, driven by a shared goal to end AIDS, is something I cherish deeply.
Conclusion: Innovation, Inclusion, and a Path Forward
Standing at this intersection of past and future on World AIDS Day 2025, I am struck by how innovation, long-term control, and inclusion have become more than buzzwords – they are the pillars of our daily work. Innovation gave us the bNAbs themselves, through advances in immunology and genomics that uncovered these rare antibodies and enabled their mass production. It continues to drive improvements like bi-specific/trispecific antibodies and gene therapy delivery of bNAbs. Long-term control is no longer a fanciful idea; it’s something we have observed in clinical trials when the right combination of bNAbs (and sometimes other agents) is used. Each incremental gain – from a few weeks of suppression to a few months – fuels our determination that sustained remission is achievable in the not-too-distant future. And inclusion is the compass that must guide us forward: scientific progress is only as meaningful as the lives it improves. Whether it’s a mother in a rural village who could benefit from an injection every six months instead of daily pills, or a young man in an urban center with multidrug-resistant HIV who needs new options – they should be front-of-mind as we develop these interventions.
Our World AIDS Day 2025 themed review blog would not be complete without acknowledging the many individuals who made this journey possible. I am grateful to all the trial volunteers who literally put their bodies on the line to test these experimental therapies – their courage is the bedrock of every advance we celebrate. I also appreciate the mentorship of pioneers in this field (some of whom are co-authors on the review) who recognized early on that neutralizing antibodies might hold the key to something big. Together, we will continue to push the envelope (pun intended) of HIV research.
In closing, writing the Behind the Paper story of our bNAb review has been a fulfilling opportunity to connect the dots between scientific research and human impact. This World AIDS Day, I stand optimistic that by investing in immune-based strategies like bNAbs, strengthening clinical partnerships in Africa and beyond, and unwaveringly committing to equity, we can transform the dream of a world without AIDS into a reality. The road is long, but with science and solidarity, we are well on our way. Continued research and collaboration will be crucial – but I have never been more hopeful that one day soon, an HIV-positive person’s journey will no longer be defined by daily therapy, but by lasting health and empowerment. That hope is what drives me, every single day, in the lab and on the front lines. Happy World AIDS Day 2025 – may it inspire us all to innovate, include, and achieve the goal of long-term HIV control for everyone.
References: Our review article in AIDS Research and Therapy (2025) provides detailed data and analysis supporting the points discussed here along with a comprehensive list of clinical trials and outcomes for those interested in the technical specifics. I invite you to read it for a deeper dive into the evidence behind this narrative. The journey of broadly neutralizing antibodies in HIV treatment is just beginning, and I am excited to see where it leads us by the next World AIDS Day.