Editor's Note: With continuous advancements in technology and deepening research in the field of AIDS prevention, new breakthroughs in HIV treatment and management have emerged. During the 25th International AIDS Conference, "Infectious Diseases Frontier" invited Dr. Hui Wang from Shenzhen Third People's Hospital and Dr. Huachun Zou from the Fudan University School of Public Health for an in-depth dialogue. They shared the latest research findings on the impact of integrase inhibitors (INSTIs) on patients' weight and BMI and discussed the challenges faced in HIV treatment and management. Furthermore, significant progress has been made in HIV prevention, with the clinical trial of Gilead's PrEP drug Lenacapavir—administered once every six months—showing remarkable results among South African women. This series of research findings not only advances the development of AIDS treatment but also provides new insights and directions for global AIDS prevention strategies.01 Infectious Diseases Frontier: Weight management is an important aspect of HIV treatment. At this AIDS conference, the team reported on the specific impact of different types of INSTIs on the BMI of treatment-naive HIV patients. Could you please introduce the background, study design, and key findings of this research?
Dr. Hui Wang: It has been confirmed through research that HIV infection can indeed lead to weight changes. In the era before integrase inhibitors, an important indicator for assessing the effectiveness of treatment and the improvement of a patient’s condition was weight. As long as there was an improvement in weight, we could preliminarily conclude that the treatment was effective. However, since integrase inhibitors entered the domestic market in 2018, many patients have switched to these treatment regimens. This raises the question of whether these regimens, particularly integrase inhibitors, have an impact on patients’ weight and BMI. This issue has been a topic of international debate. Weight is influenced by various factors, including gender, age, diet, and physical activity, all of which are constantly changing, making it difficult to attribute weight changes to a single factor. Some believe that integrase inhibitors cause weight changes, while others argue that these drugs’ milder side effects lead to overall improved health, indirectly affecting weight. Additionally, some suggest that the general population’s weight increase in recent years might be the cause, rather than the integrase inhibitors themselves. Therefore, this issue remains unresolved.
To explore this question, we collaborated with Professor Zou from Fudan University’s School of Public Health, who has extensive experience in analyzing such issues. Together, we conducted a detailed analysis of over 5,000 patients treated at our hospital between 2019 and 2023, hoping to reach a more reliable conclusion.
02 Infectious Diseases Frontier: In the study, TDF (Tenofovir Disoproxil Fumarate) and TAF (Tenofovir Alafenamide) were used in combination with other INSTIs. How do they differ in their impact on BMI?
Dr. Hui Wang: Both TDF and TAF are nucleoside reverse transcriptase inhibitors. It is widely recognized in the industry, with substantial research backing it, that TDF has a negative impact on weight. However, the effect of TAF on weight—whether neutral or positive—remains inconclusive. Therefore, in this large-sample study, we differentiated between TAF and TDF, with particular focus on TAF’s impact on weight changes and BMI in our study cohort.
Dr. Huachun Zou: Some patients or researchers might wonder whether the weight changes, especially weight gain, associated with integrase inhibitors since their introduction could be due to these drugs affecting metabolic functions.
Dr. Hui Wang: Professor Zou has raised an excellent point, which is something we have been trying to clarify. Unfortunately, no research has yet identified a specific metabolic pathway that integrase inhibitors influence, leading to metabolic disorders. Therefore, we are limited to cohort studies to observe changes in BMI and weight. However, these changes are influenced by multiple factors, which may result in some bias in the results. For instance, participants’ dietary habits, living environments, and lifestyles may differ, all of which could affect weight. If this research were conducted in a controlled environment, such as a prison, it might be more straightforward. However, this is an open cohort, so there are many influencing factors, and we can only glean some insights from it.
03 Infectious Diseases Frontier: Are the findings of this study consistent with mainstream views? Specifically, when selecting antiretroviral therapy for HIV patients, what specific recommendations do you have regarding the potential impact of INSTIs on BMI?
Dr. Huachun Zou: Our research findings are largely consistent with mainstream international research. Although integrase inhibitors cause some weight changes, we are still unclear whether these changes result from metabolic function alterations or other factors like lifestyle and dietary habits. At present, we have only obtained some hints, and further research is needed with more data to clarify the issue. However, for now, we do not recommend changing the use of integrase inhibitors solely due to weight changes, as their effectiveness and safety have been recognized, with fewer challenges to liver and kidney function and fewer side effects. Therefore, I believe that integrase inhibitors will continue to be increasingly accepted and widely used for a considerable time.
In our daily clinical work and research, I believe the collection of data such as height and weight should continue. We have found that data collection in some hospitals is not systematic, with significant gaps, which hinders our understanding of weight changes and the formulation of targeted interventions. Therefore, I encourage continuous collection of relevant information in clinical work to ensure that we have more comprehensive data for future retrospective studies.
04 Infectious Diseases Frontier: In the future, do you plan to further explore the long-term effects of INSTIs on patients’ weight and other health indicators (such as blood lipids and blood glucose)? Is a multidisciplinary management strategy necessary for the long-term management of HIV patients?
Dr. Huachun Zou: Absolutely, this is very necessary. As Professor Wang and I discussed earlier, China now has expert consensus on body fat and weight in HIV patients, indicating the increasing importance and attention these indicators receive. Many HIV patients may require long-term medication, making monitoring these indicators, among others, very important. In the future, research can be conducted from multiple perspectives. Clinicians can focus on drug treatment, viral suppression, and immune reconstitution monitoring. As a psychologist, I can provide psychological counseling support. Nutrition experts can be responsible for nutritional advice and lifestyle guidance, which are also crucial. In terms of research, we have not only clinical experts from various disciplines but also epidemiology and health statistics experts who can work together, fully utilizing data to answer scientific questions and find appropriate interventions or measures. This can benefit more patients.
Dr. Hui Wang: I believe Professor Zou has covered the topic comprehensively and excellently. Multidisciplinary collaboration may become an important direction for us in the future. As HIV treatment improves and patients live longer, metabolic issues may become more prominent, along with other emerging issues. This will likely require us to pursue a path of multidisciplinary collaboration in the future, and we hope to collaborate more with experts like Professor Zou.
05 Infectious Diseases Frontier: In your opinion, which research or topics at this AIDS 2024 conference are the most innovative or groundbreaking? How might these highlights impact AIDS research, treatment, or prevention strategies?
Dr. Huachun Zou: One of the most notable highlights of the AIDS 2024 conference is the PrEP drug Lenacapavir, developed by Gilead, which requires only one injection every six months. A study conducted among South African women found that Lenacapavir is superior to daily oral PrEP drugs, achieving 100% protection, which is incredibly encouraging. The presentation received multiple rounds of applause during the conference. This discovery adds a more effective tool to HIV prevention.
For HIV prevention, there are already multiple methods, such as PrEP and PEP, with various administration routes. In addition, other preventive measures like condom use exist. However, there are challenges with condom usage, as many funding sources may gradually reduce their financial support for this area, potentially leading to risks. Other preventive measures include circumcision, which is already recommended by WHO and the CDC for men engaging in heterosexual activity. However, for MSM (men who have sex with men) populations, this recommendation has not yet entered the guidelines. However, with new RCT studies being published, it may be included in the future.
Administering this preventive injection every six months could be a blessing for many, but it also presents challenges, such as the potentially high cost, especially in the initial years of implementation. Moreover, the injection might cause significant pain at the injection site, possibly for an extended period, which is another challenge.
Another issue is whether the duration of protection provided by this PrEP could be extended further. For example, could it last for a year or even five years? If that were possible, it would approach the effectiveness of a vaccine, presenting challenges for current vaccine research. In summary, Gilead’s PrEP drug is a highlight of this conference. We are looking forward to more data from the Lenacapavir Purpose series (Purpose 1-5). If the data from men, especially MSM populations, transgender women, and others, is as encouraging as Purpose 1’s results, it could become a historic event.
06 Infectious Diseases Frontier: Please share your outlook on the future of AIDS research and prevention efforts. In your opinion, which fields or directions will be research priorities in the future?
Dr. Hui Wang: Humanity has indeed achieved great success in AIDS treatment, but we still face challenges, such as new infections and late diagnosis. In the context of “U=U” (Undetectable = Untransmittable), I believe we still have much work to do in PrEP and PEP, especially regarding drug accessibility and public acceptance, which need improvement and refinement. Many methods need exploration, and many areas require our attention.
In terms of finding a cure, there is currently a wide range of efforts, such as Antiretroviral Treatment Interruption (ATI) studies, immunotherapy, gene therapy, and some antibody research, all aimed at curing AIDS. Which method will ultimately succeed requires further research and exploration, and this is the direction we are pursuing.
Finally, it is crucial to emphasize the importance of whole society involvement. The efforts of doctors and researchers alone are not enough, as many prevention and control efforts cannot be effectively advanced without widespread social participation. For example, how should the general HIV-negative population engage in prevention? If they are unaware of the situation, how can they effectively prevent it? A few days ago, I attended a lecture by a British expert. They have already achieved the 95-95-95 targets, but they still face many challenges. I believe one critical factor is active social participation. Only with the joint efforts of society as a whole can we make greater progress and go further on the path to ending the AIDS epidemic.
