Dr. Hongzhou Lu
Editor’s Note
The use of highly active antiretroviral therapy (HAART) has led to effective virological control in HIV-infected individuals, significantly reducing mortality rates and transforming AIDS into a treatable and manageable chronic disease. Today, one of the main clinical challenges is how to choose more “efficient and less toxic” treatment options to improve patients’ quality of life. At the 12th International AIDS Society HIV Science Conference (IAS 2023) held recently, the first randomized controlled trial on switching to integrase strand transfer inhibitor (INSTI)-based therapy to control weight gain was reported. Infectious Disease Frontier invited Dr. Hongzhou Lu from Shenzhen Third People’s Hospital, China, to interpret this trial and share insights into the current and future management of non-AIDS defining diseases (NAD) in HIV-infected individuals.
01 Research Introduction
Evaluation of a protease inhibitor-based treatment switching strategy to control weight gain associated with integrase strand transfer inhibitors: A prospective randomized trial (Abstract No: OALBB0502)
Background: Compared to treatment regimens based on non-nucleoside reverse transcriptase inhibitors (NNRTIs) or boosted protease inhibitors (PIs), integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ARV) may be associated with weight gain, especially in Black, Hispanic, and female individuals. There is currently no prospective randomized data exploring the impact of switching ARV drug classes on mitigating or reversing ARV-related weight gain.
Methods: The DEFINE study (NCT04442737) is a randomized (1:1), prospective, 48-week, active-controlled, open-label, multicenter phase IV study aimed at evaluating virological suppression in HIV-1-infected adults who experienced a weight gain of 10% or more during treatment with INSTI-based regimens when switched to darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) or continued INSTI+TAF/emtricitabine (FTC). The primary objective was to assess the percentage change in weight from baseline to week 24 for patients in both groups. Data up to week 24 are reported herein.
Results: A total of 103 patients were randomized, with 53 in the D/C/F/TAF group and 50 in the INSTI+TAF/FTC group; 30% were female, and 61% were Black/African American (Table 1). At week 24, the percentage change in weight from baseline was an increase of 0.63% in the D/C/F/TAF group and a decrease of 0.24% in the INSTI+TAF/FTC group, with no significant difference between the two groups (P=0.2349) (Figure 1A). The majority of patients in both groups had weight change rates within ±3%, and body mass index and waist circumference remained within baseline classification ranges. Weight change percentages for major subgroups are shown in Figure 1B. Switching to D/C/F/TAF was safe, well-tolerated, and maintained efficacy.
Table 1. Baseline Characteristics
Figure 1. Percentage Change in Weight Compared to Baseline
Conclusion: For adult patients experiencing INSTI-related weight gain, switching from an INSTI-based regimen to D/C/F/TAF for 24 weeks did not result in a significant difference in weight change. Additional analyses are ongoing, including follow-up at week 48 and assessments of biomarkers and body composition (dual-energy X-ray absorptiometry, DEXA).
02 Expert’s Review
Infectious Disease Frontier: In an oral presentation at this conference, there was an RCT study (Abstract No: OALBB0502) that explored a switching strategy based on PI regimens to control INSTI-related weight gain. How do you view this switching medication strategy?
Dr. Lu: We know that weight gain is related to diet and exercise, and if patients can increase their physical activity and restrict their diet in daily life, their weight will not increase significantly. In clinical practice, we have encountered many patients with weight gain, and after targeted health education, the weight gain in these patients was effectively controlled. Many ARV drugs in the past had gastrointestinal side effects such as nausea and vomiting, but INSTIs had relatively fewer side effects. Therefore, for patients who switch to INSTI-based regimens, their dietary habits may improve, and correspondingly, their weight may increase. This is one of the reasons that affect patients’ weight changes. On the other hand, PI drugs such as lopinavir/ritonavir often cause diarrhea, and the degree of diarrhea is severe. If patients use these drugs for a long time, it will inevitably lead to weight loss. Therefore, the impact of PIs or INSTIs on weight needs to be assessed comprehensively, including the impact of dietary habits and gastrointestinal symptoms such as diarrhea.
Considering the excellent viral suppression and minimal side effects of INSTIs, their treatment advantages are very clear. Regimens containing INSTIs can be considered the best treatment option at present. Therefore, I do not currently recommend switching patients to PI-based regimens. In this case, how can we control INSTI-related weight gain? I believe that we should start with patient health management. During follow-up, we should conduct a detailed assessment of the patient’s weight and lifestyle habits and provide appropriate intervention measures based on the assessment results. At the same time, we should emphasize balanced diet and moderate exercise as part of a healthy lifestyle to actively prevent weight gain. This is a very important aspect of our clinical work.
Infectious Disease Frontier: In the oral presentations on clinical research at this IAS conference, non-AIDS defining diseases (NAD) such as weight gain, lipid disorders, and hypertension accounted for a significant proportion. Why do you think it is important to focus on the management of NAD in HIV patients in the current era of ART treatment?
Dr. Lu: The advent of antiretroviral therapy (ART) has transformed AIDS into a manageable chronic disease, significantly extending the lifespan of patients. With the prolonged survival and aging of HIV-infected individuals, they, like other populations, may experience chronic and age-related diseases. Moreover, the optimization of highly effective and low-toxicity treatment regimens has reduced gastrointestinal adverse reactions, improved the quality of life of patients, and led to better dietary habits. This has made weight gain, elevated lipid levels, and other NAD more common. Therefore, long-term health management of patients is required. Healthcare providers need to closely monitor patients for related symptoms and implement appropriate interventions, including pharmacological interventions if necessary.
NAD such as weight gain and lipid disorders are not only on the rise internationally but are also significant issues faced by domestic patients. In order to better screen for and manage such NAD, our experts in the field of infectious diseases have collaborated to develop the “Chinese Expert Consensus on Comprehensive Management of Lipids in HIV/AIDS Patients.” In fact, many infectious disease specialists do not have in-depth knowledge of lipid management. The development of this consensus has drawn our attention to the lipid abnormalities that exist among us medical professionals and has prompted us to regulate lipid levels through lifestyle and medication interventions. Therefore, I believe that the development of this consensus is a valuable health education for healthcare professionals like us. If even medical professionals need this kind of education, how much more so for patients without a medical background? Through this systematic review of knowledge related to comprehensive lipid management, I believe that specialists like us can pay more attention to the management of NAD in HIV-infected individuals. With our firsthand experience and knowledge, we can better choose appropriate intervention methods for patients. Furthermore, health education is also an effective intervention method. Doctors can impart knowledge of lipid management to patients, benefiting both healthcare providers and patients.
Infectious Disease Frontier: NAD management involves multiple disciplines, including infectious diseases, cardiology, endocrinology, and more. How can we leverage the strengths of multiple disciplines to participate in the management of NAD?
Dr. Lu: In the development of this consensus, we invited experts from cardiology, lipid management, hypertension, and other fields, such as Dr.Li Yong from the Department of Cardiology at Fudan University Affiliated Huashan Hospital. The development of the consensus reflects interdisciplinary collaboration. In the clinical management of NAD, as a designated hospital for AIDS treatment, Shenzhen Third People’s Hospital has also adopted a multidisciplinary collaborative model for comprehensive patient diagnosis, treatment, health education, and management. We will adhere to this model and hope to promote it in more designated hospitals.
Infectious Disease Frontier: What other research questions related to NAD do you think are worth exploring? China has a large population of HIV/AIDS patients. How can we integrate resources and data for more high-quality research?
Dr. Lu: I believe that we have a large number of cohort studies that can be used to conduct national multicenter research through these cohorts. We can make full use of patient resources to conduct baseline investigations and health education interventions. In addition, there is basic research and mechanistic research, and mechanistic research is more complex, and we have not yet fully clarified it. In terms of basic research, we have sufficient patient resources and basic research teams. Therefore, we should develop our own research in this area and conduct corresponding translational research to turn basic research results into clinical interventions.
Infectious Disease Frontier: At this IAS conference, which areas of research are you particularly interested in?
Dr. Lu: Functional cure of AIDS is an important task for us. Functional cure and the development of an AIDS vaccine are still major challenges globally. I believe that there will be significant progress in the functional cure of AIDS in the future. My team is also conducting research on related topics, and I believe that Chinese research teams will achieve excellent results in this field and make important contributions internationally.
Reference:
[1] W.R. Short, et al. A prospective, randomized trial to assess a protease inhibitor–based regimen switch strategy to manage integrase inhibitor–related weight gain. IAS 2023; Abstract OALBB0502.
