Abstract
Background
Long-term evidence from resource-limited settings spanning transitions in HIV care is scarce. We describe 25-year outcomes from a pragmatic Indian cohort employing simplified regimens and strategic drug sequencing.
Methods
Treatment-naïve adults initiated dual-nucleoside reverse transcriptase inhibitor therapy (2000-2025), reserving protease and integrase inhibitors for later lines (“class preservation”). Primary outcomes were survival and treatment durability.
Results
Among 971 patients retained in care (12,438 patient-years), Kaplan-Meier survival was 95.8% at 5 years and 88.3% at 25 years. Median first-line durability was 8.3 years. Overall, 85% achieved ≥95% adherence. Opportunistic infection incidence declined from 451.5 to 69.7 per 1000 patient-years. Clinically driven monitoring saved US$7578 per patient.
Conclusions
For patients retained in continuous care, strategic sequencing, intensive adherence support, and provider continuity sustained durable outcomes over 25 years. These findings characterize outcomes achievable under sustained engagement rather than population-level results.
Plain Language Summary Title
Long-term HIV care in India: What 25 years in a resource-limited clinic teaches us about survival, affordable medicines, and helping patients take their daily pills
Plain Language Summary
HIV is now a manageable condition, but delivering lifelong care in areas with limited financial and medical resources is highly challenging. Most global health guidelines rely on expensive lab tests and newer, costly drugs. This raises an important question: how can doctors provide long-term care when patients cannot afford these standard options? This study looks at 25 years of HIV care at a single independent clinic in southern India, from 2000 to 2025. To keep care affordable and effective, the clinic used a highly practical approach. Patients were started on simple, lower-cost combinations of older HIV drugs. The newer, more expensive drugs were strictly saved as backup options, to be used only if the first medicines stopped working. Because routine blood tests to check virus levels were too expensive for most patients, the clinic focused heavily on human support instead of technology. The doctor counted the patients' pills every month to ensure they were not missing doses, proactively treated any side effects before they became severe, and provided continuous, personal encouragement. The results showed this strategy was highly successful. Among the patients who stayed with the clinic for the continuous 25-year period, nearly 90% survived and lived healthy lives. On average, their first, lowest-cost drug combination kept them healthy for over eight years before a change was needed. Furthermore, only performing lab tests when clinically necessary saved over $7,500 per patient compared to standard international guidelines. This study proves that in areas with limited technology, expensive medical tests are not the only path to success. Strong doctor-patient relationships, affordable drug planning, and careful monitoring of daily pill-taking can sustain HIV care for decades.
Keywords
Introduction
The global scale-up of antiretroviral therapy (ART) has transformed HIV from a fatal disease into a manageable chronic condition, with major reductions in morbidity and mortality worldwide.1,2 Since the mid-2000s, ART access has expanded rapidly across low- and middle-income countries (LMICs), enabling millions to initiate lifelong treatment.
Most evidence guiding current HIV policies comes from randomized trials and cohorts in settings with stable health systems, routine laboratory monitoring, and broad drug availability.3,4 While these studies establish efficacy, they offer limited insight into long-term outcomes under routine service delivery in resource-constrained environments, particularly across periods of health system transition.
As a result, several critical evidence gaps remain insufficiently addressed. These include the absence of long-term outcomes extending beyond two decades, limited data spanning periods before and after national ART program scale-up, scarce evidence from independent, non-programmatic care models, and little documentation of pragmatic drug-sequencing strategies implemented under sustained diagnostic and therapeutic constraints. Addressing these gaps is essential to understanding how long-term HIV care can be maintained in resource-limited settings (RLSs) outside controlled program environments.
In India, the early epidemic was marked by delayed diagnosis, restricted drug access, and high out-of-pocket costs before free national ART services began in 2004. During this time, independent practices provided care that balanced effectiveness with affordability despite limited diagnostics. Long-term data from such pragmatic models remain scarce, especially those spanning both pre- and post-program eras. Evidence from these contexts may inform strategies for sustaining HIV care where resources remain constrained.
While HIV emerged globally during the 1980s, sustained antiretroviral access in many LMICs lagged by more than a decade, becoming widely available only after World Health Organization (WHO)-led scale-up from 2004 onward. As a result, cohorts in RLSs often have shorter cumulative treatment exposure and different sequencing histories than those informing contemporary guidelines. Long-term observational evidence from such contexts therefore remains essential to understand how guideline principles translate into durable care under routine conditions.
At the time of this cohort initiation in 2000, three-drug antiretroviral combinations were universally recommended by international guidelines.5,6 The concept of simplified two-drug initial or maintenance regimens was not yet established. Importantly, the use of simplified regimens in this cohort reflected a pragmatic, context-driven strategy to sustain long-term treatment access and sequencing under constrained conditions, rather than an attempt to replace or challenge prevailing guideline recommendations. During much of the early and mid-program period, triple-drug regimens incorporating protease inhibitors were financially inaccessible to most self-paying patients, intermittently available, or incompatible with sustained outpatient adherence in the absence of routine laboratory monitoring, necessitating alternative sequencing approaches focused on long-term affordability and feasibility.
Over the subsequent two decades, accumulating evidence from randomized trials demonstrated that selected two-drug combinations incorporating high-genetic barrier agents (protease inhibitors or integrase inhibitors) could achieve non-inferior outcomes in selected patients.7-14 This evolution from universal three-drug therapy to acceptance of strategic two-drug approaches offers context for understanding the historical regimens utilized in this cohort. In this RLS, limited affordability and availability of protease inhibitors, integrase inhibitors, and routine viral load monitoring required pragmatic strategies prioritizing feasibility and long-term sustainability. Such program-level adaptations remain highly relevant for long-term HIV care delivery in RLS where diagnostic and therapeutic options continue to be constrained.
We therefore report 25-year clinical and treatment outcomes from adults initiating ART at an independent HIV practice in southern India between 2000 and 2025, spanning both pre- and post-national ART program eras. Specifically, we examine long-term survival, treatment durability, and pragmatic drug class preservation strategies implemented under constrained diagnostic and therapeutic conditions, with outcomes explicitly conditional on sustained engagement in care.
Methods
Study Design and Setting
This study is a retrospective analysis of data derived from a prospective observational cohort of treatment-naïve adults living with HIV who initiated ART at an independent HIV care practice in southern India. The cohort was established in November 2000 and followed through November 2025. Consistent single-provider oversight was maintained throughout the 25-year period.
The cohort represents a dynamic, real-world population with continuous enrollment over time. Following the national scale-up of free ART services in 2005 (in the study area), many clinically stable patients transitioned to government programs for medication access and disability benefits. Treatment distributions reflect patients retained in care as of November 2025 (Table 1).
Baseline Characteristics of the Retained Cohort (N = 971).
Abbreviations: IQR, interquartile range; ART, antiretroviral therapy; WHO, World Health Organization; CD4, Cluster of Differentiation 4.
Baseline CD4 testing was performed only when financially feasible (n = 97) and was not a prerequisite for treatment initiation in this pragmatic cohort.
“Other” regimens include abacavir/lamivudine and didanosine/lamivudine, which were primarily utilized during the early program eras (2000-2010).
Care was delivered under routine outpatient conditions with simplified regimens and selective monitoring typical of resource-limited practice environments.
Cohort Assembly, Follow-up, and Censoring
A total of 7170 treatment-naïve adults initiated ART at the study center between November 2000 and November 2025. Of these, 5833 patients met eligibility criteria for inclusion in the dual- nucleoside reverse transcriptase inhibitor (NRTI) cohort (Figure 1). During longitudinal follow-up, 971 patients (16.7%) remained in continuous care at the study center through November 2025 and constituted the analytic cohort for long-term outcome assessment.
Cohort flow and follow-up status of patients initiating ART (2000-2025). Patients transferring to government ART programs were censored at the time of transfer, as post-transfer clinical outcomes were not available. Long-term survival and durability analyses were restricted to patients retained in continuous care at the study center. ART, antiretroviral therapy.
The remaining 4862 patients exited direct care at the study center. As detailed in Figure 1, this included 2236 patients (46.0%) who transferred to government-operated ART programs, 1751 patients (36.0%) who were lost to follow-up (LTFU), and 875 patients (18.0%) who died prior to transfer. Among the 971 patients retained in continuous care, an additional 103 deaths were documented and 11 patients were subsequently LTFU.
Clinical outcomes after transfer to government programs were not available to the investigators and could not be ascertained. Accordingly, patients who transferred out were censored at the time of transfer. All survival, treatment durability, and morbidity estimates presented in this analysis therefore apply exclusively to patients who remained engaged in continuous follow-up at the study center and should be interpreted as conditional on retention in care rather than population-level outcomes for all ART initiators.
Study Population
Adults aged ≥18 years with confirmed HIV-1 infection and no prior antiretroviral exposure were eligible if clinically stable for outpatient ART initiation. Clinical stability criteria were assessed to balance treatment initiation with available monitoring capacity in this RLS. Stability was defined pragmatically as the ability to take oral medication, absence of life-threatening opportunistic infections (such as severe respiratory failure or acute cryptococcal meningitis) requiring hospitalization, and willingness to attend monthly follow-up.
Patients were excluded if they presented with pregnancy, prior antiretroviral exposure, or advanced disease requiring initial three-drug therapy. These patients received standard three-drug ART when clinically feasible but were excluded from this specific analysis to evaluate the durability of simplified regimens. This restriction was intentional to evaluate long-term durability of simplified regimens under outpatient conditions and does not imply applicability to patients requiring urgent induction with three-drug therapy.
Antiretroviral Treatment Strategies
Antiretroviral strategies evolved across five program eras (2000-2025), shaped by drug affordability, availability, and the gradual expansion of national ART services.
Therapy was initiated using dual-NRTI combinations. As tenofovir became available (2008 onward), it progressively replaced older NRTIs, though stable patients on stavudine continued therapy to minimize costs. 3TC or FTC was sometimes continued for formulation availability and affordability, despite the possibility of little residual antiviral activity after prolonged prior exposure. Regimen sequencing nevertheless aimed to ensure that at least two agents with expected full activity were combined at each treatment stage. Upon failure, patients transitioned to a boosted protease inhibitor plus a new NRTI. Third-line regimens, established from 2016, utilized dolutegravir or alternative protease inhibitors. Complete regimen evolution and era-specific protocols are detailed in Table 2.
Regimen Evolution and Treatment Strategy.
Abbreviations: d4 T, stavudine; 3TC, lamivudine; AZT, zidovudine; ddI, didanosine; TDF, tenofovir disoproxil fumarate; ABC, abacavir; TAF, tenofovir alafenamide; FTC, emtricitabine; LPV/r, lopinavir/ritonavir; ATV/r, atazanavir/ritonavir; DTG, dolutegravir; DRV/r, darunavir/ritonavir; PI, protease inhibitor; ART, antiretroviral therapy; NRTI, nucleoside reverse transcriptase inhibitor.
Note. Percentages represent regimen distribution among patients receiving care during that era, not the full inception cohort.
Class preservation strategy: Dual-NRTI regimens were utilized to preserve protease inhibitors for second-line use. Percentages reflect the mix of regimens used by patients active in that specific era.
Second-line: Consistently utilized a boosted PI with a nucleoside backbone not previously used (eg, switching from d4 T to TDF). 3TC/FTC was continued in fixed-dose combinations to maintain affordability.
Third-line strategy: Suspected second-line failure based on clinical/immunologic criteria, with virologic confirmation when available. Third-line therapy was typically initiated after prolonged treatment exposure (total ART duration 12-18 years).
Regimen selection (in order of preference): 1. DTG (50 mg OD) + New NRTI: Prioritized for high-genetic barrier, once-daily dosing, tolerability, and lower cost than PIs; 2. Alternative PI + New NRTI: Used if DTG unavailable. Strategy involved switching PIs with different resistance profiles (eg, if LPV/r failed → switch to ATV/r, and vice versa); 3. Salvage (DRV/r): Darunavir/ritonavir + Unused NRTI reserved for extensively treated patients with multi-class resistance.
Adherence Support and Retention
Adherence support was the cornerstone of the care model, utilizing a “high-touch, low-tech” approach to ensure durability. The program employed a multimodal strategy representing feasible adherence infrastructure in outpatient settings with limited resources:
Measurement and Counseling: Pill counts were performed at every monthly visit as the primary adherence measure, supplemented by structured physician-led counseling. Every consultation addressed barriers to medication-taking, missed doses, and family support dynamics. Proactive Toxicity Management: To sustain adherence to older regimens (like stavudine or zidovudine), the program proactively managed anticipated toxicities. Interventions included prophylactic methylcobalamin for neuropathy, ferrous ascorbate for anemia, and nutritional support for wasting. This anticipatory care reduced treatment interruptions due to intolerance. Financial and Logistical Support: Recognizing economic barriers, the care center utilized generic sourcing and bulk purchasing to subsidize medication costs. Economically disadvantaged patients received sliding-scale fees. Missed appointments triggered immediate active follow-up via phone to prevent loss to follow-up.
Although pill counts and self-report have inherent limitations, they were sufficient for routine clinical decision-making in this setting and were reinforced by frequent provider contact and long-term continuity of care. While pill counts have recognized limitations and are subject to manipulation, they represented the most feasible adherence metric available in this RLS. Importantly, the clinical outcomes observed, including median first-line durability of 8.3 years and virologic suppression >90% among tested patients provide indirect clinical validation that the pill count-based adherence monitoring, when supplemented by frequent provider contact and longitudinal continuity, achieved its intended programmatic goal of sustaining treatment adherence.
Monitoring and Clinical Management
Baseline evaluation included WHO clinical staging, tuberculosis (TB) screening, and essential laboratory investigations. CD4 cell counts and viral load testing were performed selectively based on financial feasibility and clinical indication rather than routine scheduled monitoring. Routine hepatitis B testing was not performed as first-line regimens consistently included agents with anti-HBV activity (lamivudine, tenofovir).
Routine antimicrobial prophylaxis with cotrimoxazole or isoniazid preventive therapy was not systematically administered during the early program periods. This reflected prevailing local practice patterns and resource constraints at the time, with a programmatic emphasis on intensive clinical surveillance to detect and treat active disease promptly rather than routine prophylactic suppression. Under this model, TB was actively identified and managed on an outpatient basis, resulting in 1855 treated episodes, of which 68.8% occurred within the first year of ART initiation, without the need for hospitalization. This context-specific approach should not be interpreted as a recommendation against guideline-supported prophylaxis and may not be appropriate outside settings with close clinical follow-up and rapid access to diagnostic evaluation and treatment.
CD4 and viral load testing became progressively more available in later program eras; however, routine virologic testing remained largely unavailable in early eras (<5% of patients in Eras 1 and 2). We estimate that by Eras 4 and 5, approximately 30% of patients received at least annual CD4 monitoring and 10% received annual viral load monitoring. Accordingly, immunologic and virologic response data are more complete after 2010 but should be interpreted descriptively rather than as uniform cohort-wide measures.
Outcomes and Statistical Analysis
Primary outcomes were survival and treatment durability (time to failure). Treatment durability was defined as the time from ART initiation to discontinuation of the first-line regimen for any cause. Treatment failure was physician adjudicated based on available criteria: (1) Clinical failure (new or recurrent WHO Stage 3 or 4 condition after ≥6 months of therapy); (2) Immunologic failure (CD4 count fall to baseline or below, or a > 50% decline from on-treatment peak, requiring one confirmatory test); or (3) Virologic failure (viral load ≥1000 copies/mL, when testing was accessible). Regimen switches were not mandatory upon isolated laboratory abnormalities; rather, they were individualized clinical decisions weighing the risk of resistance against limited future sequencing options. Data were analyzed using SPSS Version 25.0 (IBM Corp, Armonk, NY). Time zero was defined as the date of ART initiation. The primary endpoints were survival and time to treatment failure. Survival probabilities were estimated using the Kaplan-Meier method. Censoring occurred at the date of the last clinic visit for patients who were LTFU or transferred to government centers. Patients who transferred out were censored at the time of transfer as their subsequent outcomes (death or survival) could not be reliably ascertained by the private clinic. Descriptive statistics (medians, IQRs) were used for continuous variables. A two-sided P-value <.05 was considered statistically significant where applicable. Given the pragmatic, retrospective nature of the cohort, missing CD4 or viral load data were not imputed; analyses relied on available case data.
Results
Between 2000 and 2025, a total of 7170 treatment-naïve adults initiated ART. Of these, 5833 met eligibility criteria for the dual-NRTI cohort (Figure 1). By November 2025, 971 patients (16.7%) remained in continuous follow-up with complete data, while 4862 exited direct care (2236 transferred to government programs, 1751 were LTFU, and 875 died) (Figure 1).
Survival and Treatment Durability
Among the 971 patients in the continuous care cohort, the mean duration of follow-up was 12.8 years (SD: 6.1). Baseline characteristics are summarized in Table 1. As of November 2025, 857 patients (88.3%) were alive and receiving ART, 103 (10.6%) had died, and 11 (1.1%) were LTFU. Kaplan-Meier estimates of survival were 95.8% at 5 years and 88.3% at 25 years (Figure 2). These estimates reflect outcomes among patients retained in continuous follow-up at the study center and do not include patients who transferred to government programs, whose outcomes could not be ascertained. These outcomes reflect patients who remained engaged in continuous care and do not capture outcomes following transfer or loss to follow-up.
Long-term survival probability. Kaplan-Meier estimate of overall survival among 971 patients retained in continuous care over 25 years. The solid line indicates survival probability (88.3% at 25 years); shaded areas represent 95% confidence intervals.
The median time to first-line treatment failure was 8.3 years (95% CI: 7.8-8.9). Notably, 650 patients, including patients enrolled in eras 3, 4, and 5 (75.9% of those alive), remain on their initial dual-NRTI first-line regimen. First-line durability was observed across all regimens based on sustained tolerability and economic feasibility. Durability varied by initial regimen: 8.1 years for stavudine/lamivudine, 9.8 years for zidovudine/lamivudine, and 11.4 years for tenofovir-based regimens (P < .001).
As of November 2025, 252 patients were receiving second-line therapy. Third-line therapy was initiated in 71 patients (7.3%), of whom 69 remain on active third-line or salvage treatment.
Morbidity and Opportunistic Infections
A total of 2753 opportunistic infection episodes were recorded. Incidence declined from 451.5 per 1000 patient-years (years 1-2) to 69.7 per 1000 patient-years (year 5+). TB was the most frequent infection (1855 episodes), peaking in the first year of ART. This pattern reflects the high burden of prevalent and subclinical disease at presentation in this endemic setting.15-19 All episodes were managed on an outpatient basis. TB remained the leading cause of mortality (39.8% of deaths). The concentration of TB mortality and early TB episodes (68.8% within year 1) reflects the burden of prevalent and subclinical disease at presentation in this high-endemic setting, consistent with immune reconstitution inflammatory syndrome and disease unmasking rather than failure of the ART strategy itself.15-19 The dramatic subsequent decline in overall opportunistic infection incidence (from 451.5 to 69.7 per 1000 patient-years beyond year 5) confirms effective long-term immune restoration despite the initial TB burden. Other infections included bacterial pneumonia (223), herpes zoster (134), and cryptococcal meningitis (28) (Table 3).
Long-Term Morbidity, Mortality, and Economic Outcomes (2000-2025).
Abbreviations: OI, opportunistic infection; TB, tuberculosis. *Virologic suppression (<50 copies/mL) rates are calculated from the subset of patients who underwent viral load testing upon clinical indication or availability (n = 124).
Projected costs are estimated based on standard private-sector pricing for guideline-recommended monitoring frequencies (quarterly viral load and CD4 counts) over the 25-year period.
Tuberculosis episodes include both pulmonary and extrapulmonary cases. All recorded episodes were managed on an outpatient basis.
OI incidence rates were calculated from 12,438 patient-years of observation.
CD4 change estimates are based on patients with available longitudinal CD4 measurements and should be interpreted as descriptive.
Adherence and Economics
Among all 5833 patients who received care, 4956 (85.0%) achieved ≥95% adherence. Within the continuous follow-up cohort (N = 971), mean adherence was 96.8% (SD: 4.2%). Mean total ART-related expenditure was US$ 5397 per patient over 25 years. Clinically driven monitoring resulted in estimated savings of US$ 7578 per patient compared with guideline-recommended laboratory surveillance (Table 3).
Discussion
Principal Findings
This 25-year cohort from a RLS in India demonstrates that durable HIV care is achievable when consistent implementation strategies are applied despite constraints in laboratory capacity and drug availability. Survival remained high, treatment durability was sustained, and morbidity declined markedly among patients retained in continuous care. These outcomes highlight the importance of implementation quality over intensive laboratory monitoring in RLS.
Evolution of Two-Drug Therapy in Context
The dual-NRTI regimens employed in this cohort (2000-2025) were initiated during an era when such approaches contradicted prevailing guidelines. A small cohort study on dual-NRTI therapy in treatment-naive patients was presented as early as 2004 at the International Symposium on HIV & Emerging Infectious Diseases, 20 demonstrating outcomes during an era when international guidelines universally recommended three-drug induction therapy for all treatment-naive adults.
The intervening two decades have witnessed a paradigm shift. Multiple randomized controlled trials have now validated the concept of two-drug maintenance therapy, though with critical differences from the approach used here. Contemporary two-drug regimens incorporate high-genetic barrier agents either boosted protease inhibitors (GARDEL, 2014 7 ) or integrase inhibitors (GEMINI, 2019 10 ; TANGO, 2020 12 ) combined with a single NRTI, typically lamivudine.
The dual-NRTI strategy documented here differs fundamentally: it preserved high-barrier agents for later treatment lines rather than incorporating them at initiation. Where companion drugs such as 3TC/FTC were retained for fixed-dose availability, sequencing aimed to ensure that at least two agents with expected full activity were combined at each treatment stage. This class preservation approach, necessitated by limited drug availability and absent routine viral load monitoring in the early 2000s, reflects a principle now recognized as essential in RLSs: strategic sequencing of antiretroviral classes to maximize long-term treatment options while preserving future therapeutic options.21-24 The continued use of stavudine in stable patients during middle eras requires clarification. Stavudine was maintained exclusively in patients who had tolerated it without significant toxicity for prolonged periods and for whom switching posed financial barriers. Anticipated toxicities were proactively managed with methylcobalamin supplementation and nutritional support. Patients developing significant lipodystrophy or neuropathy were switched to tenofovir when financially feasible. While stavudine's toxicity profile is well-established and its use is no longer recommended, its retention here reflects the real-world economic constraints that characterized HIV care in this era and setting.
Contemporary guidelines now endorse two-drug regimens in specific contexts,22-24 reflecting accumulated evidence that regimen simplification when appropriately designed can sustain virologic control. The durability observed in this cohort (median first-line duration 8.3 years) suggests that intensive adherence support and careful sequencing may contribute to prolonged treatment success, even in the absence of high-barrier agents at initiation. These findings underscore that in resource-constrained environments, implementation quality may be as influential as regimen composition in determining long-term outcomes. This has particular relevance for long-term HIV programs in RLS where laboratory capacity remains uneven.
Role of Implementation and Adherence Infrastructure
Adherence support proved decisive. The program's infrastructure including pill counts, proactive side effect management, subsidized medication access, and single-provider oversight enabled most patients to maintain high adherence. These low cost but labour-intensive interventions were arguably more influential than regimen composition in determining long-term outcomes. While pragmatic, manual pill counts are inherently susceptible to behavioral biases, including the “white-coat effect” or “pill dumping” prior to clinic visits. To mitigate this risk, pill counts were not used in isolation but were triangulated with high-touch, consistent physician continuity, and proactive management of side effects to foster an environment of honest patient reporting. Together, these findings suggest that continuity, adherence infrastructure, and strategic sequencing may compensate for technological constraints and sustain long-term treatment success.
Strengths, Limitations, and Policy Implications
This study provides rare program-level evidence spanning 25 years of HIV care in an independent practice in India, reflecting long-term outcomes under routine service conditions with constrained laboratory and therapeutic resources. Key strengths include the duration of follow-up, consistent single-provider oversight, pragmatic adherence infrastructure, and detailed documentation of treatment sequencing strategies across multiple program eras. However, several limitations should be noted. The 16.7% retention rate (971 of 5833 patients) represents a critical limitation requiring explicit acknowledgment. This low completion rate introduces substantial survivorship and selection bias, as outcomes are conditional exclusively on sustained retention rather than representative of all ART initiators. While baseline characteristics were similar between retained and exited patients, unmeasured factors influencing retention (treatment tolerance, social stability, economic capacity) likely also influenced survival, potentially inflating observed survival estimates. Importantly, the majority of exits (46%) were transfers to government programs following national ART scale-up rather than treatment failure or death, reflecting health system transitions rather than clinical outcomes. However, without post-transfer vital status data, we are unable to perform intent-to-treat survival analysis or sensitivity analyses incorporating alternative LTFU outcome scenarios. The reported 88.3% 25-year survival therefore represents the upper bound of achievable outcomes under optimal retention conditions and should not be extrapolated to population-level ART program survival. This methodological constraint underscores the importance of linked health information systems enabling cross-facility outcome ascertainment in settings with high patient mobility. Laboratory monitoring was selective and not uniformly available across the study period, limiting virologic confirmation of treatment failure. Consequently, the reliance on clinical and immunologic monitoring in early eras likely masked instances of silent virologic failure. The absence of routine viral load monitoring raises concerns about undetected virologic failure and accumulated drug resistance. In settings without universal VL access, asymptomatic resistance or virologic failure in clinically and immunologically stable patients can persist for extended periods until clinical failure becomes apparent, potentially compromising future treatment options and contributing to risk of transmitted resistance. This “low-tech” monitoring approach carries inherent risks: delayed recognition of treatment failure, prolonged exposure to failing regimens fostering resistance mutations, and reduced effectiveness of subsequent lines with shared patterns of class resistance. In the current era of rising pretreatment and acquired drug resistance globally, particularly to NRTIs and NNRTIs, reliance on clinical/immunologic monitoring alone is no longer considered safe or adequate. Our cohort reflects historical realities of the early-to-mid ART era (2000-2015) when VL testing was prohibitively expensive and unavailable in most RLSs. While this approach enabled treatment access for patients who would otherwise have received no therapy, we explicitly do not recommend this model for contemporary practice. Current WHO guidelines appropriately prioritize routine VL monitoring as the standard of care, and programs should invest in VL infrastructure even in resource-constrained settings. Point-of-care VL technologies and task-shifted sample collection models now make universal monitoring increasingly feasible and should be implemented to detect failure promptly, preserve treatment options, and minimize resistance amplification. Finally, as a single-center observational cohort, findings may not be fully generalizable to other settings, but they remain highly relevant for long-term HIV care delivery in resource-limited outpatient contexts. From a policy perspective, these findings imply that in settings where advanced diagnostic infrastructure is delayed or unavailable, investing heavily in clinic-level adherence infrastructure and provider continuity can still yield highly durable survival outcomes.
Conclusions
Among patients retained in continuous care over 25 years, adults in this Indian cohort achieved high survival and durable treatment under a pragmatic care model. Success rested on three pillars: reliable medication access, intensive adherence support, and strategic sequencing of drug classes. The evolution of global guidelines toward acceptance of simplified two-drug regimens, albeit with different drug combinations, reflects a similar underlying principle: that strategic treatment design, when paired with robust implementation, may sustain virologic control in appropriately selected patients. These findings offer a roadmap for sustaining HIV care in RLSs, demonstrating that durable outcomes depend not only on pharmacologic advances but fundamentally on implementation quality, including adherence infrastructure, provider continuity, and strategic treatment sequencing. These findings support the importance of adherence infrastructure, continuity, and feasible sequencing strategies for long-term ART delivery in settings where laboratory monitoring and regimen options remain constrained.
Footnotes
Acknowledgements
The author gratefully acknowledges the patients of Lakshmi Vaidyasala for their trust and resilience over 25 years. The author gratefully acknowledges the support of his wife, Mrs. Geetha Yanamadala, for her sustained personal support throughout the conduct of this work. The author also thanks the nursing and administrative staff who supported patient care and record-keeping throughout the study period. The author received language-editing assistance using ChatGPT 5.2 (OpenAI) and Claude Sonnet 4.5 (Anthropic) to improve clarity and formatting. All scientific content, analysis, and interpretations remain the author's responsibility.
Ethical Approval and Informed Consent
This study was a retrospective analysis of routinely collected clinical data that were fully anonymized prior to analysis. In accordance with the Indian Council of Medical Research (ICMR) National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (2017), specifically Section 5, Box 5.2 regarding anonymized retrospective data, formal institutional ethics committee approval and additional informed consent for research participation were not required. The study protocol was reviewed administratively by the Institutional Ethics Committee of Lakshmi Vaidyasala, Kakinada, India, and was granted exemption from full review (IEC Ref No: LV/IEC/2026/Pragmatic HIV care-02). All patients had previously provided written informed consent for HIV treatment and routine clinical data recording at the time of treatment initiation. The study adhered to the principles of the Declaration of Helsinki.
Consent for Publication
Not applicable. The manuscript contains no individual person's data, identifying details, images, or videos.
Author Contributions
MKY is the sole author. He conceived the study, provided clinical care to the cohort over the 25-year period, oversaw data collection, performed the statistical analysis, and drafted the manuscript. The author read and approved the final manuscript.
Funding
The author received no financial support for the research, authorship, and/or publication of this article.
Declaration of Conflicting Interests
The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Data Availability Statement
The datasets generated and/or analyzed during the current study are not publicly available due to the sensitive nature of HIV clinical data and the potential risk of participant identification within a single-center cohort. However, de-identified aggregate data supporting the findings of this study are available from the corresponding author upon reasonable request and subject to ethical considerations.