Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF) Treatment in People Living with HIV: A Single-Center Real-World Experience from Belgrade, Serbia

In the era of modern antiretroviral therapy (ART), focus has expanded beyond viral suppression to the broader issues of overall health, quality of life, and comorbidity management for people living with HIV. The burden of non-communicable comorbidities, including cardiovascular disease (CVD), chronic kidney disease (CKD), and osteoporosis, is becoming more pronounced as this population ages. Thus, modern ART aims not only to prevent disease progression but also to ensure long-term safety, minimize treatment-related toxicities, and reduce cardiovascular and metabolic risks.

The non-nucleoside reverse transcriptase inhibitor doravirine (DOR) is available as a single drug, to be used as part of an ART regimen, and also co-formulated with lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) in a once-daily fixed-dose tablet [1]. According to the most recent European AIDS Clinical Society (EACS) guidelines, doravirine-based combinations are recommended both for initiating ART in treatment-naïve individuals and for switching therapy in patients who are virologically suppressed [2]. Phase III clinical trials confirmed that DOR achieved efficacy similar to standard ART regimens, while also demonstrating a reassuring safety record [1]. Unlike earlier non-nucleoside reverse-transcriptase inhibitors (NNRTIs), DOR was developed to enhance tolerability, reduce neuropsychiatric and lipid-related side effects, provide a stronger resistance barrier, and minimize drug–drug interactions, with the added benefit of not requiring food intake [2,3]. Follow-up studies and real-world data consistently support its sustained efficacy, good safety profile, and neutral effect on metabolism [1].

In Serbia, DOR/3TC/TDF became available in May 2024. In this report, we present demographic and clinical characteristics of our cohort of people living with HIV, including both treatment-naïve patients initiating and treatment-experienced patients switching to this regimen, along with early outcomes related to virological suppression and lipid profile.

This retrospective study was carried out at the Department of HIV/AIDS, Clinic for Infectious and Tropical Diseases, University Clinical Centre of Serbia. Between May 2024 and April 2025, 260 patients had either initiated DOR/3TC/TDF as their initial ART regimen or switched to this combination from a prior antiretroviral therapy. All were included, except those with incomplete data. Our clinic currently follows approximately 2000 people living with HIV, predominantly male, with a median age of 34 years; 52% identify as men who have sex with men (MSM). The cohort has been prospectively maintained since 1985. We retrieved data from electronic medical records, including demographic characteristics (age, sex, HIV acquisition route), clinical history (high blood pressure, diabetes mellitus, osteoporosis, hepatitis B (HBV) or hepatitis C (HCV) coinfection, prior ART), treatment history, adverse events (AEs), and treatment discontinuations. Laboratory analyses (CD4+ T-cell count, HIV-1 RNA, triglycerides, total cholesterol, and low-density lipoprotein [LDL] cholesterol), which were the most consistently available in patient records, were assessed for patients with available paired measurements, which explains variation in sample size (n) across laboratory parameters. Baseline laboratory assessment and patient monitoring were performed at initiation and subsequently every 6-12 months. However, not all the patients had complete paired data due to variations in adherence and delayed visits. We applied descriptive methods: normally distributed data are expressed as means and standard deviations, non-normal variables as median with interquartile ranges (IQR), and categorical variables as counts with percentages. Categorical variables were compared between groups using the Chi-square test. Laboratory results before and after initiation of DOR/3TC/TDF were assessed with either the paired t-test or the Wilcoxon signed-rank test, depending on distribution. Statistical significance was established at p <0.05.

The mean age was 42.0±10.8 years, and the majority were male (93.8%). The predominant mode of HIV-1 acquisition was sex between men (65.8%), followed by heterosexual contact (16.2%). The most common comorbidities were high blood pressure (16.9%) and diabetes mellitus (5%). Coinfection with HBV and HCV was observed in 7.3% and 4.2% of patients, respectively. Of the 260 individuals analyzed, 41 (15.8%) were treatment-naïve, and 219 (84.2%) had switched from a prior ART regimen, with a median time from HIV diagnosis to initiation of DOR/3TC/TDF of 72 months (IQR: 24-108 months). The most frequent previous regimens included an NNRTI (40.4%), an integrase strand transfer inhibitor (INSTI) (38.8%), or a protease inhibitor (PI) (5%). Table 1 displays the baseline demographic, clinical, and treatment characteristics. The main reasons for switching were regimen simplification, avoidance of potential drug-drug interactions, and improved tolerability.

Laboratory findings are presented in Table 2. The median follow-up in this analysis was 7 months (IQR: 1-11 months). Among treatment-naïve patients, CD4+ T-cell counts increased significantly (458±312.0 vs. 580.7±262.8 cells/µL, p=0.007). Viral load declined markedly (median 279738 [1381-4620000] vs. 23.7 [0-326] copies/mL, p=0.001) with 82.8% achieving undetectability at follow-up. Among switched patients, CD4+ T-cell counts remained stable (665.0±317.7 vs. 660.5±268.0 cells/µL, p=0.891), and viral suppression was largely maintained, with the proportion undetectable increasing from 83.2% to 93.1% (p=0.013). In the available subset of patients with paired data, no significant short-term changes were observed in lipid parameters during follow-up. No cases of virological failure were observed. One patient discontinued DOR/3TC/TDF because of a rash, but no other adverse events were recorded during the follow-up.

To our knowledge, this is the first report on a real-world use of DOR/3TC/TDF in Serbia. At the end of 2023, approximately 3427 people were living with diagnosed HIV in Serbia. Late presentation remains frequent (up to 50%), and stigma continues to hinder early testing and treatment. Serbia has reached about 75-85% diagnosis coverage, 70-80% ART uptake among those diagnosed, and 70-80% viral suppression among those on therapy. Our cohort receiving DOR/3TC/TDF reflects key characteristics of the local population of people living with HIV in Belgrade, predominantly middle-aged MSM, with hypertension and diabetes as common comorbidities. A notable proportion had an unclear mode of acquisition, likely reflecting persistent stigma. Despite comorbidities and long prior ART exposure, patient outcomes were satisfactory: no cases of virological failure were observed, CD4+ T-cell counts remained stable, and only one individual discontinued therapy due to rash. Our finding therefore supports short-term effectiveness and good tolerability of DOR/3TC/TDF in routine practice. These results are in line with evidence from pivotal trials and observational studies. In DRIVE-FORWARD and DRIVE-AHEAD, doravirine-based regimens achieved virological control comparable to ritonavir-boosted darunavir and efavirenz, while producing fewer neuropsychiatric adverse events and demonstrating a more favorable lipid profile [1]. The DRIVE-SHIFT study further confirmed sustained suppression following treatment switch [4]. Our experience also parallels European real-world data, such as the multicountry DREW study, which reported virological success rates above 90% and excellent tolerability in both switch and naïve populations at week 48 [5].

We observed no significant changes in total cholesterol, LDL, or triglycerides after switching to DOR, in line with previous reports of its lipid-neutral profile. Although no weight gain was reported in our cohort during follow-up, the short observation period and incomplete weight data precluded formal statistical evaluation. Our analysis was limited to triglycerides, total cholesterol, and LDL cholesterol, while other metabolic and safety parameters were not systematically collected.

This study has certain limitations. Resistance testing, weight monitoring, BMI, other biochemical parameters, comorbidities, and drug-drug interactions were not systematically assessed. Renal, bone, and hepatic safety parameters were also not systematically assessed, and broader safety conclusions cannot be drawn from our data. In addition, not all the patients had complete paired laboratory data despite routine monitoring every 6-12 months. Its retrospective, single-center design, and relatively short follow-up further limit the extent to which the findings can be generalized. Nevertheless, the analysis provided important real-world evidence, supporting the efficacy, safety, and metabolic neutrality of DOR/3TC/TDF in routine clinical practice in Serbia.

In an ageing population of people living with HIV, antiretroviral regimens need to balance sustained efficacy with long-term safety. Our results indicate that once-daily DOR/3TC/TDF was well-tolerated in both treatment-naïve and switch patients, with virological suppression maintained and no significant short-term changes in lipid parameters during the follow-up period. Combined with European real-world evidence, these findings support the role of doravirine-based therapy as a practical option in routine HIV management, including in the Serbian setting.