Comparison Of Clinical Stadium Changes And Immunologic Parameter Of Adult HIV patients With Dolutegravir And Efavirenz Based Antiretroviral Therapy

Introduction

Human immunodeficiency virus (HIV) infection remains a major global public health challenge. According to the World Health Organization, approximately 39.9 million people were living with HIV worldwide in 2023, with around 1.3 million new infections occurring annually.¹ The widespread implementation of antiretroviral therapy (ART) has substantially reduced HIV related morbidity and mortality and improved the life expectancy of people living with HIV (PLWH) by suppressing viral replication and restoring immune function.²

The primary goal of ART is to achieve sustained viral suppression, prevent disease progression, and restore immune function, commonly assessed through the recovery of CD4+ T-cell counts.^2,3 Without treatment, HIV infection leads to progressive depletion of CD4+ lymphocytes, resulting in immune dysfunction and increased susceptibility to opportunistic infections and advanced clinical stages of the disease.⁴ Early initiation of ART has been shown to significantly reduce disease progression and improve long term clinical outcomes.^5,6

For many years, efavirenz based regimens were widely used as the standard first-line therapy for HIV infection. Earlier international guidelines recommended a regimen consisting of tenofovir, lamivudine (or emtricitabine), and efavirenz as the preferred initial therapy for adults and adolescents.² However, increasing resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), including efavirenz, as well as concerns regarding adverse effects, prompted the search for more effective antiretroviral agents.^3,7,8

Dolutegravir, an integrase strand transfer inhibitor (INSTI), has emerged as a potent antiretroviral agent with several advantages compared with earlier regimens. Evidence from clinical trials and meta-analyses has demonstrated that dolutegravir based therapy provides higher rates of viral suppression, a higher genetic barrier to resistance, and improved tolerability compared with efavirenz based regimens.^9,10,11 Based on this growing body of evidence, the World Health Organization recommended dolutegravir based antiretroviral therapy as the preferred first-line regimen for adults and adolescents in updated treatment guidelines.^12,13

In addition to improved virological outcomes, dolutegravir has also been associated with enhanced immunological recovery. Several studies have reported greater increases in CD4+ cell counts among patients receiving dolutegravir based therapy compared with those receiving non-nucleoside reverse transcriptase inhibitor-based regimens, including efavirenz.⁷ Nevertheless, findings across different settings remain inconsistent, and some studies have reported comparable immunological outcomes between the two regimens during early treatment periods.¹⁴

Despite the growing global adoption of dolutegravir based regimens, evidence comparing clinical and immunological outcomes between dolutegravir and efavirenz remains limited in many low- and middle-income countries, including Indonesia. Local real-world data are important to evaluate the effectiveness of ART regimens in specific populations, as treatment outcomes may be influenced by factors such as baseline immunologic status, opportunistic infections, adherence to therapy, and healthcare access. Furthermore, monitoring both clinical stage progression and immunologic recovery provides a comprehensive evaluation of treatment response in patients with HIV.^2,9,10

Therefore, this study aimed to compare the changes in clinical stage and immunologic parameters among adult HIV patientss receiving dolutegravir based and efavirenz based antiretroviral therapy at Wahidin Sudirohusodo Hospital. The findings of this study are expected to provide additional evidence regarding the effectiveness of these ART regimens in a real-world clinical setting and contribute to optimizing HIV treatment strategies in Indonesia.

Methods

Results

Discussion

This study compared clinical stage changes and immunologic parameters among adult patients with HIV receiving dolutegravir based and efavirenz based antiretroviral therapy at Dr. Wahidin Sudirohusodo Hospital. Several important findings emerged from this analysis.

First, the majority of patients in this study presented with advanced HIV disease at the time of treatment initiation, as reflected by the high proportion of individuals in WHO clinical stages III–IV and CD4 counts below 200 cells/mm³ ( Table 1). This finding suggests that many patients begin antiretroviral therapy only after significant immune deterioration has occurred. Similar patterns have been reported in several studies from low- and middle-income countries, where delayed diagnosis and barriers to healthcare access contribute to late presentation of HIV infection. Reports from World Health Organization indicate that late presentation remains a major challenge in HIV management globally, particularly in resource-limited settings.^15,16,17

Second, our study found no significant difference in baseline clinical stage between patients receiving dolutegravir based and efavirenz based regimens ( Table 2). This indicates that the two treatment groups were relatively comparable at the start of therapy. Baseline comparability is important in observational studies because it reduces the potential influence of confounding factors when evaluating treatment outcomes.^9,10,15

Third, this study demonstrated that age was not significantly associated with either clinical stage or immunologic status ( Table 4 and 5). Both younger and older patients showed similar distributions of clinical stage and CD4 levels. These findings suggest that factors other than age—such as duration of untreated infection, adherence to therapy, or presence of opportunistic infections—may play a more important role in determining disease severity at presentation.^2,5,18

Another important finding in this study was that no statistically significant difference in clinical stage improvement or CD4 recovery was observed between patients receiving dolutegravir based therapy and those receiving efavirenz based therapy during the study period ( Table 2 and 3). Although dolutegravir is widely recognized as a potent integrase strand transfer inhibitor with a high genetic barrier to resistance, our findings suggest that both regimens may provide comparable clinical and immunologic outcomes in real-world clinical settings.^9,10,13

Previous clinical trials have demonstrated the superior virologic efficacy of dolutegravir based regimens compared with efavirenz based therapy. For example, randomized trials reported higher viral suppression rates and improved tolerability among patients receiving dolutegravir-containing regimens.^10,19 These findings contributed to the global recommendation by the World Health Organization that dolutegravir based therapy should be the preferred first-line antiretroviral regimen for adults and adolescents with HIV.^2,13

However, the absence of a significant difference in our study may be explained by several factors. First, this study evaluated clinical stage and CD4 count, which are indirect markers of treatment response, rather than viral load suppression, which is the primary endpoint in many randomized clinical trials.^2,10,19 Second, the retrospective nature of this study and the limited follow-up period may have reduced the ability to detect subtle differences between treatment regimens.²⁰ Third, variations in adherence, comorbid conditions, and access to healthcare services may influence treatment outcomes in routine clinical practice.²¹

Our findings are consistent with several observational studies conducted in routine clinical settings that reported similar immunologic recovery between dolutegravir and efavirenz regimens, particularly during the early phases of treatment.^10,22 This suggests that while dolutegravir may provide superior virologic efficacy in controlled trials, real-world outcomes may be influenced by multiple contextual factors.^2,19

This study has several strengths. First, it provides real-world evidence regarding the clinical and immunologic outcomes of different antiretroviral regimens in a tertiary referral hospital in Indonesia. Second, the study included a relatively large sample of patients receiving routine HIV care, allowing for the evaluation of treatment outcomes in a practical clinical setting.

However, several limitations should be acknowledged. The retrospective design may introduce potential biases related to incomplete medical records and unmeasured confounding variables. In addition, viral load data were not available for all patients, limiting the ability to directly assess virologic suppression. Furthermore, the study was conducted in a single tertiary hospital, which may limit the generalizability of the findings to other healthcare settings.

Despite these limitations, this study provides valuable insights into the clinical outcomes of patients receiving different antiretroviral regimens in routine clinical practice. Future prospective studies with longer follow-up periods and comprehensive virologic monitoring are needed to further evaluate the comparative effectiveness of dolutegravir- and efavirenz based therapies.

In conclusion, most patients in this cohort initiated antiretroviral therapy at advanced stages of HIV infection with severe immunosuppression. No significant differences were observed in clinical stage improvement or CD4 recovery between dolutegravir based and efavirenz based antiretroviral regimens. These findings highlight the importance of early HIV diagnosis and treatment initiation to improve clinical outcomes among people living with HIV.

Ethical consideration

The study received ethical approval from the Biomedical Research Ethics Commission of the Faculty of Medicine, Hasanuddin University, Makassar with Ethical Approval Letter Number 102/UN4.6.4.5.31/PP36/2026 Informed consent was obtained from all participants.