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Abstract

Emerging evidence from the REPRIEVE study cohort has further clarified the association between abacavir use and cardiovascular risk. This analysis, along with previous findings, demonstrates a significant elevation in time to first major adverse cardiovascular events (MACE) among adults living with HIV with current or past abacavir exposure. Given the availability of safer, equally effective alternative ART regimens with fewer cardiovascular risks, the continued clinical relevance of abacavir in adults living with HIV should be critically reassessed. Considering these findings, abacavir should be considered an obsolete option for most, if not all, adults living with HIV. This perspective shift emphasizes the importance of selecting ART regimens that optimize long-term cardiovascular health while achieving durable virologic suppression in the modern era of HIV treatment.

Keywords

abacavir antiretrovirals cardiovascular disease HIV

The intersection of HIV and cardiovascular disease

People living with HIV (PWH) are at an increased risk of cardiovascular disease (CVD), driven by persistent inflammation and immune activation.¹ This risk may be further exacerbated by comorbidities, modifiable lifestyle choices such as smoking, and adverse effects of select antiretroviral medications. Moreover, recent data indicate that biological sex influences immune response and inflammatory markers in PWH. For instance, women initiating antiretroviral therapy (ART) early have demonstrated a protective effect against CVD not observed in men.²

The link between CVD and HIV is further complicated as, despite transformative advancements in HIV management, many modern ART regimens have been implicated, or are hypothesized to contribute, to cardiometabolic disease.³ While ART achieves virologic suppression and immunologic restoration in most PWH, HIV itself can induce permanent alterations in inflammatory mediators and hyperimmune activation, perpetuating the risk of CVD, even after virologic control is achieved.

Notably, PWH have an approximately two-fold increased risk of experiencing cardiovascular events, indicating the critical need for primary prevention of atherosclerotic CVD (ASCVD) in this population.⁴ The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) trial demonstrated the efficacy of primary cardiovascular prevention with pitavastatin, achieving a 35% reduction in major adverse cardiovascular events (MACE) over a median of 5.1 years in PWH with low to moderate traditional cardiovascular risk.⁵ Notably, this reduction exceeded expectations based solely on low-density lipoprotein cholesterol (LDL-C) lowering, suggesting additional pleiotropic benefits of statin therapy.⁶

While no ART regimen has definitively demonstrated direct cardiovascular benefit, certain antiretrovirals, such as abacavir, have been associated with an increased risk of CVD events. This association has been consistently demonstrated across multiple studies and diverse patient populations,^7
–14 rendering the continued use of abacavir in modern ART regimens indefensible, particularly given the availability of safer and equally effective alternatives.

The global “expiration” of abacavir in adult PWH and the subsequent shift away from its use emphasize the critical importance of ART selection that prioritizes CVD risk mitigation and optimizes long-term health outcomes for this population.

Abacavir: Historical context and evolving clinical utility

Abacavir, a nucleoside reverse transcriptase inhibitor (NRTI) approved in 1998, was initially released as a single agent and later incorporated into fixed-dose combinations.¹⁵ Its initial widespread use and incorporation into clinical guidelines were driven by favorable drug attributes, including good tolerability, few adverse effects, and non-renal elimination via alcohol dehydrogenase. These features made abacavir particularly attractive for patients with impaired renal function, including those requiring hemodialysis.

However, the introduction of tenofovir alafenamide (TAF)-containing regimens, which are now indicated for use in patients requiring hemodialysis without dose adjustment, and other two-drug ART regimens, has significantly diminished the role of abacavir in adult populations.¹⁶ Its clinical utility is further constrained by the risk of severe hypersensitivity reactions, necessitating HLA-B*5701 screening prior to initiation.¹⁷ This requirement poses a significant barrier in settings where delayed test turnaround times hinder its use in rapid ART initiation programs.

This review aims to critically examine the clinical evidence demonstrating increased cardiovascular risks and suboptimal virologic outcomes associated with abacavir compared to alternatives, providing actionable recommendations for clinical practice.

Reconsidering abacavir initiation in adults with HIV

Presentation of a brief case

A cisgender man in his late 50s presented for ART initiation following a recent HIV diagnosis. His medical history includes a 40-pack-year smoking history, type 2 diabetes, dyslipidemia with elevated serum LDL-C, and obesity, with a body mass index (BMI) of 35 kg/m².

Baseline laboratory investigations revealed a CD4 count of 470 cells/mm³ and a plasma HIV-1 RNA viral load of 750,680 copies/mL. Genotypic resistance testing did not identify any known drug resistance mutations. HLA-B*5701 screening was negative. Hepatitis B surface antigen (HBsAg) testing was negative. He expressed a strong preference for a once-daily single-tablet regimen to simplify his treatment and was initiated on dolutegravir/lamivudine/abacavir.

Clinical evidence elucidating the complicated role of abacavir-containing ART

The clinical utility of abacavir-containing ART has been extensively scrutinized due to efficacy concerns in specific populations, its durability in the presence of antiretroviral mutations, and evolving therapeutic alternatives.

In 2011, the AIDS Clinical Trials Group (ACTG) 5202 study demonstrated that abacavir/lamivudine was less effective as an NRTI backbone than tenofovir disoproxil fumarate/emtricitabine in PWH with high baseline viral loads (HIV-1 RNA ⩾ 100,000 copies/mL) when combined with efavirenz or atazanavir/ritonavir.¹⁸ These findings suggested the need for caution when considering an abacavir-containing regimen in patients with elevated baseline viremia.

The introduction of a single-tablet regimen combining abacavir with dolutegravir and lamivudine in 2014 partially addressed concerns about the efficacy of abacavir.¹⁹ The high potency of dolutegravir and lack of widespread integrase strand transfer inhibitor resistance mutations mitigated fears of suboptimal virologic suppression.²⁰ Moreover, the STRIIVING study demonstrated non-inferiority of switching to abacavir/lamivudine/dolutegravir, temporarily overshadowing previously acknowledged concerns about the inferior virologic outcomes associated with abacavir.²¹

However, the impact of resistance mutations, particularly the M184V/I mutation, further complicates the role of abacavir in ART. The M184V/I mutation confers more than a 200-fold reduction in susceptibility to lamivudine and emtricitabine and approximately a threefold reduction to abacavir.^22,23 While M184V/I alone does not significantly compromise in vivo virologic response,²⁴ its coexistence with thymidine analogue mutations (TAMs) further reduces abacavir susceptibility. In contrast, tenofovir retains partial efficacy despite the presence of TAMs and exhibits enhanced activity in the presence of M184V, making it the preferred NRTI in regimens to treat virus harboring M184V and additional TAMs.^25,26 Furthermore, there is a growing body of evidence that despite the presence of M184V, dual therapy with lamivudine and dolutegravir maintains viral suppression, further minimizing the clinical benefit of abacavir-containing single tablet regimens.²⁷

Unlike tenofovir formulations, which have potent antiviral activity against both HIV and hepatitis B virus (HBV), abacavir lacks significant hepatitis B viral suppression capacity. Consequently, abacavir is not recommended for patients with HIV/HBV coinfection, necessitating documented HBV immunity or exclusion of HBV infection prior to its initiation. Historically, abacavir was also an attractive option for PWH with decreased bone mineral density (BMD), as it was available in fixed-dose combinations and associated with fewer bone-related adverse effects compared to tenofovir disoproxil fumarate.²⁸ However, the availability of tenofovir alafenamide has sufficiently addressed concerns, as tenofovir alafenamide demonstrates similar bone safety as other NRTIs, effectively relegating abacavir to a lesser role in this population.

Based on these findings, the role of abacavir in modern ART continues to diminish, particularly in the presence of superior backbone NRTIs such as tenofovir disoproxil fumarate or tenofovir alafenamide, which offer better resistance profiles, broader applicability, and enhanced utility across diverse patient populations.^26,29,30

Proposed mechanisms of cardiovascular toxicity associated with abacavir

The potential association between abacavir use and increased cardiovascular risk has been a topic of ongoing debate since its initial emergence in observational studies. Several investigations have suggested an elevated risk of myocardial infarction (MI) among PWH receiving abacavir-containing ART.^7,9
–12 However, these findings remain controversial due to conflicting evidence and methodological concerns, including selection or channeling bias, where individuals at higher baseline cardiovascular risk may have been more likely to receive abacavir-containing regimens.

Despite the lack of consensus regarding a causal link, several mechanistic hypotheses have been proposed to explain a potential relationship between abacavir and increased cardiovascular risk. These include increased platelet activation,³¹ hyperlipidemia,³² T-lymphocyte activation,³³ endothelial dysfunction,^34,35 increased pro-inflammatory biomarkers,³⁶ impaired monocyte-derived macrophage proliferation with increased reactive oxygen species (ROS) and inflammatory cytokine production,³⁷ and endoplasmic reticulum stress and activation of the unfolded protein response in human astrocytes.³⁸ Another hypothesis implicates the structural similarity of abacavir to endogenous purines in triggering prothrombotic and proinflammatory signaling.³⁹ Of these, abacavir-induced platelet aggregation, hyperreactivity, and leukocyte recruitment promoting noncalcified atherosclerotic plaque formation have been demonstrated in several in vivo studies.^40
–43 While these hypotheses provide plausible mechanisms linking abacavir to cardiovascular events, definitive evidence remains elusive, further compounded by conflicting data and limitations in available studies.

Clinical evidence of cardiovascular disease in PWH treated with abacavir

Evidence supporting the cardiovascular risks of abacavir has been inconsistent, with early analyses such as a 2012 meta-analysis conducted by the U.S. Food and Drug Administration (FDA) aggregating data from 26 clinical trials and reporting no statistically significant association between abacavir use and MI (odds ratio 1.02, 95% CI: 0.56–1.84).⁴⁴ However, additional investigations have provided more robust evidence supporting concerns about the role of abacavir in cardiovascular risk (Table 1).^7
–14

Table 1.

Overview of select studies showing the association of abacavir with cardiovascular toxicity.

Study citation	Intervention (study design, sample size, outcome, exposure to abacavir, reference group)	Clinical findings, relevance
Sabin et al.⁷	International, prospective cohortN = 33,347MIRecent, cumulativeOther ARV agents*People with prior CVD were allowed into the study	Recent use of abacavir: RR 1.90 (1.47–2.45)Cumulative use of abacavir: RR 1.14 (1.08–1.21)Increased risk of MI in patients exposed to abacavir within the preceding 6 months.
Martin et al.⁸	Australia, randomized controlled trialN = 357CVDRecentTenofovir disoproxil fumarate/emtricitabine*People with prior CVD were allowed into the study	HR 0.12 (0.02–0.98)Lower rate of CV events among participants who received tenofovir, compared to abacavir.
Obel et al.⁹	Denmark, prospective cohortN = 2952MICurrentUnexposed to abacavir*People with prior MI were included in the study	RR adjusted for confounders 2.00 (1.10–3.64)Abacavir is associated with an increased risk of MI.
Lang et al.¹⁰	France, Case–controlN = 1173MIRecent, cumulativeUnexposed to abacavir*People with prior MI were included in the study	Recent use of abacavir: OR 1.62 (0.93–2.81)Cumulative use of abacavir: OR 0.97 (0.86–1.10)Patients with recent use of abacavir had a significantly increased risk of MI, whereas cumulative exposure to abacavir was not.
Durand et al.¹¹	Quebec, Case–controlN = 1209MIRecentUnexposed to abacavir*People with prior MI or stroke were included in the study	Adjusted OR for any exposure 1.79 (1.16–2.76)Adjusted OR for recent exposure 1.72 (1.10–2.71) Abacavir is associated with increased OR for MI with either any or current exposure.
Choi et al.¹²	USA Veterans Health Administration, Retrospective cohortN = 10,931CVD, MIRecent, cumulativeARVs other than tenofovir and abacavir*People with prior CVD were allowed into the study	Recent use of abacavir and CVD: HR 1.48 (1.08–2.04)Cumulative use of abacavir and CVD: HR 0.93 (0.79–1.10)Recent use of abacavir and MI: HR 1.64 (0.88–3.08)Recent abacavir use was significantly associated with incident cardiovascular events.
Young et al.¹³	Switzerland, Prospective cohortN = 11,856CVDRecent, cumulativeUn-exposed to abacavir*People with prior CVD were allowed into the study	Recent use of abacavir: HR 1.63 (1.14–2.32)Cumulative use of abacavir: 1.22 (0.98–1.52)Recent, but not cumulative, exposure to abacavir increased the risk of a CVD event. In a new marginal structural Cox model, continued exposure to abacavir during the past 4 years increased the risk of a CVD event (HR 2.06 (1.43–2.98)).
Jaschinski et al.¹⁴	Europe/Australia, Prospective cohortN = 29,340CVDRecentNo recent abacavir use*People with prior CVD were allowed into the study	Adjusted HR 1.40 (1.20–1.64)Recent abacavir use was associated with increased CVD incidence independent of other risk factors.

*The asterisk denotes a key point regarding which comorbidities were allowed or included in the referenced studies whereas this was not true in all studies described.

CVD, cardiovascular disease, HR, hazard ratio, MI, myocardial infarction, OR, odds ratio, RR, relative risk.

A retrospective analysis of the REPRIEVE trial evaluated prior and current exposure to abacavir and tenofovir-containing regimens and their association with subsequent CVD events.⁴⁵ The primary endpoint for this analysis was similar to that of the seminal study, which evaluated time to first major adverse cardiovascular events (MACE), including cardiovascular death, MI, hospitalization for unstable angina, stroke, transient ischemic attack, peripheral arterial ischemia, revascularization, or death of indeterminate cause. Secondary endpoints included time to first hard MACE and its components, which consisted of cardiovascular death, stroke, and MI.

To assess differential risk based on regimen exposure, the investigators conducted sensitivity analyses stratified by participants from high-income countries, with additional adjustment for race, and by duration of current NRTI use (<1 year). Inverse probability of censoring weighting (IPCW) was employed to account for treatment switching over time and to better estimate relative exposure effects.

Of those randomized in REPRIEVE, 6114 participants were eligible for evaluation. The majority were receiving TDF (n = 4,274), followed by TAF (n = 957) and abacavir (n = 883). Participants with abacavir or TAF exposure were more likely to be older males (>50 years), have a higher ASCVD risk score, lower estimated glomerular filtration rate (eGFR), and a history of substance use. Other baseline characteristics, including CD4 count, pre-existing hypertension, and smoking status, were similar between those with and without abacavir exposure.

The analysis revealed a significant association between abacavir use and an elevated risk of MACE. Although not statistically significant, baseline-adjusted hazard ratios indicated a 40% increased risk of first MACE for abacavir versus TDF (HR 1.4, 95% CI: 0.9–2.1) and a 50% increase versus TAF (HR 1.5, 95% CI: 0.9–2.3). The authors acknowledged the lack of statistical significance but posit that the confidence intervals remained compatible with a harmful association. The largest effect estimates were observed in comparisons of individual MACE components: the risk of MI was notably higher with abacavir versus TDF (IPCW HR 3.5, 95% CI: 1.3–9.4), and stroke risk was elevated with abacavir versus TAF (IPCW HR 2.9, 95% CI: 0.9–9.8).

The majority of individuals receiving abacavir (n = 751, 84%) resided in high-income global burden of disease (GBD) regions. Sensitivity analyses limited to high-income GBD regions revealed similar trends: abacavir was associated with increased MACE risk compared to TAF (HR 1.6, 95% CI: 1.0–2.5) and TDF (HR 1.3, 95% CI: 0.8–2.1), while no difference was observed between TAF and TDF (HR 0.8, 95% CI: 0.5–1.4). Notably, adjustment for race did not result in a difference in the findings, despite prior evidence suggesting higher CVD risk among Black or African American individuals.⁴⁶ Additional analyses limited to participants with < 1 year of current NRTI use (abacavir, n = 334) also demonstrated elevated MACE risk for abacavir compared to TAF (HR 1.5, 95% CI: 0.7–3.2) and TDF (HR 1.5, 95% CI: 0.7–3.5), with no difference between TAF and TDF (HR 1.0, 95% CI: 0.5–2.1).

Similarly, findings from the REPRIEVE study, presented at the 25th International AIDS Conference in July 2024, offer compelling additional evidence regarding the cardiovascular safety of abacavir.⁴⁷ This analysis evaluated prior and current exposure to abacavir at study entry compared to no exposure and risk of CVD events. At baseline, 22% reported prior abacavir exposure, and 13% were receiving abacavir, with a median duration of 1.47 years. Baseline characteristics, including age, CD4 count, rates of virologic suppression, and hypertension rates, were similar between those with and without abacavir exposure. However, individuals with abacavir exposure were more likely to be male, White, and from higher-income regions. The median ASCVD risk score was slightly higher in the abacavir-exposed group (5.4% vs 4.2%).

The analysis found a significantly higher incidence of MACE over 96 months of follow-up among individuals with prior (9.74%) and current (7.63%) abacavir exposure compared to those with no exposure (3.74%). After adjusting for potential confounders, including age, sex, race, CVD risk factors, and baseline ART regimen, individuals with a history of abacavir use had a 50% increased risk of MACE, and those with current use had a 42% increased risk compared to those with no abacavir exposure.

Interestingly, no significant differences were observed between groups in the individual components of cardiovascular death, MI, or stroke after adjustment, suggesting that the elevated MACE risk may be driven by nonfatal or less severe cardiovascular events. Importantly, the increased cardiovascular risk observed with abacavir was not replicated with other antiretrovirals, including protease inhibitors, thymidine analogs (zidovudine or stavudine), or TDF. This specificity strengthens the argument that the cardiovascular effects of abacavir are distinct and potentially related to idiosyncratic mechanisms.

These findings, when considered alongside prior data comparing NRTI backbones, indicate that abacavir is associated with an increased risk of MACE, even in individuals with low to moderate baseline cardiovascular risk.⁴⁵ Notably, although MACE risk was elevated, the lack of significant differences in cardiovascular death, MI, or stroke in this analysis contrasts with other studies reporting increased risk for these outcomes. Several factors may contribute to the observed discrepancy between increased MACE and similar rates of fatal cardiovascular events, including competing risks, survival biases, and potential discrepancies in outcome measurement or categorization may also contribute to the observed findings. Despite these complexities, abacavir use was associated with a markedly increased risk of MACE, highlighting its potential impact even in individuals with minimal traditional cardiovascular risk factors.

Follow-up to the brief case

The presented case of a cisgender man in his late 50s initiating ART with dolutegravir/lamivudine/abacavir raises important considerations regarding modern ART selection. While the patient’s preference for a single-tablet regimen is understandable to promote adherence, his significant cardiovascular risk factors, including a substantial smoking history, type 2 diabetes, dyslipidemia with elevated LDL-C, and obesity, alongside the availability of alternative, potentially safer and equally efficacious agents, warrant a critical re-evaluation of the chosen regimen.

Mounting evidence has associated abacavir use with an increased risk of cardiovascular events, particularly in individuals with pre-existing cardiovascular disease or risk factors. This association, while debated in its exact mechanism and magnitude across various studies, necessitates caution, especially in patients like the one described.

Furthermore, the efficacy of TDF and, more recently, TAF as components of first-line ART regimens is well established. These agents, often combined with other effective drugs in single-tablet formulations, offer comparable or even superior virologic suppression in many patient populations without the same level of concern regarding cardiovascular safety. TAF, in particular, demonstrates improved renal and bone safety profiles compared to TDF, making it an attractive option for many individuals.

Given the patient’s considerable cardiovascular risk profile and the availability of highly effective and potentially safer alternatives like TDF or TAF-based regimens, the initiation of abacavir in this context appears suboptimal and potentially exposes the patient to unnecessary cardiovascular risk.

We argue that abacavir should no longer be considered for initial ART in adults with HIV, especially those with pre-existing cardiovascular risk factors. The potential for increased cardiovascular toxicity, coupled with the proven efficacy and generally favorable safety profiles of tenofovir-based options, strongly supports a paradigm shift away from routine abacavir initiation.

This case reinforces the critical need for clinicians to carefully weigh individual patient characteristics, including cardiovascular risk, alongside patient preferences when selecting ART. While single-tablet regimens are valuable for adherence, this benefit should not outweigh the potential for increased harm when safer and equally convenient alternatives exist. Future guidelines and clinical practice should emphasize the prioritization of tenofovir-based regimens (TDF or TAF, where appropriate) over abacavir for the majority of ART-naïve adults with HIV, particularly those with cardiovascular risk factors.

Modern role of abacavir in ART and strategies for transition

Presentation of a brief case

A cisgender woman in her early 40s presents to the clinic for a routine 6-month follow-up for HIV. She has been consistently virologically suppressed on abacavir/lamivudine/dolutegravir for the past 5 years, with no reported complaints or adverse events. Baseline genotypic resistance testing prior to initiating ART revealed no resistance mutations, and she has never experienced virologic failure. In addition, serologic testing confirmed immunity to HBV.

Despite achieving and maintaining virologic suppression and absence of clinically evident CVD, her 10-year ASCVD risk score was 5% (borderline risk). After a thorough discussion of the potential cardiovascular risks associated with continued abacavir use, a decision is made to switch her regimen to dolutegravir/lamivudine. This modification eliminates abacavir from her current ART, thereby potentially reducing her cardiovascular risk while maintaining virologic suppression. Statin therapy was initiated with atorvastatin 20 mg daily for the primary prevention of ASCVD.

Abacavir in modern ART

Due to the requirement for HLA-B*5701 screening, mounting data linking abacavir to increased cardiovascular risk, and the availability of safer, equally effective alternatives, abacavir use has become limited to select clinical scenarios. This shift is reflected in updated recommendations from the U.S. Department of Health and Human Services (HHS) and the International Antiviral Society-USA (IAS-USA) guidelines, both of which de-emphasize abacavir as a first-line option.^16,48 Similarly, the European AIDS Clinical Society (EACS) has also recently designated abacavir as an alternative NRTI.⁴⁹ These changes have prompted many clinicians, including the authors of this review, to actively transition patients off abacavir-containing regimens regardless of CVD risk.

Evidence supporting the transition away from abacavir

For individuals who are virologically suppressed (HIV RNA < 50 copies/mL) on abacavir-containing ART, switching to abacavir-free regimens maintains durable suppression.^50
–52 Options for non-abacavir-containing ART include the single-tablet regimen bictegravir/emtricitabine/tenofovir alafenamide, dual oral maintenance therapies such as dolutegravir/lamivudine, dolutegravir/rilpivirine, or ritonavir-boosted darunavir plus lamivudine, and the long-acting injectable regimen cabotegravir/rilpivirine.^50
–52

Among these, dolutegravir/lamivudine has demonstrated robust and durable efficacy in randomized controlled trials, establishing itself as a reliable option for treatment-naïve and treatment-experienced individuals.⁵³ The DOLCE study further evaluated dolutegravir/lamivudine in low- and middle-income countries (LMICs), including among “late presenters” with advanced HIV (CD4 count < 200 cells/mm³), and found it to be both highly effective and well-tolerated.⁵⁴ These findings further support the removal of abacavir from treatment recommendations in LMICs, where logistical challenges such as limited access to HLA-B*5701 testing, difficulties in screening and monitoring cardiovascular risk, high rates of presentation with advanced HIV, and the imperative of immediate treatment initiation often render abacavir-based regimens impractical.

By transitioning to abacavir-free regimens, clinicians can mitigate the risk of abacavir-associated hypersensitivity reactions and cardiovascular events, thereby simplifying patient care and reducing the need for ongoing cardiovascular risk assessments. This approach aligns with modern treatment priorities, emphasizing the optimization of both safety and convenience for individuals living with HIV. Furthermore, the availability of diverse treatment options allows for the personalization of ART regimens based on individual patient factors, such as treatment history, comorbidities, and personal preferences. This personalized approach not only enhances treatment adherence and improves patient quality of life but also contributes to the long-term success of HIV treatment and prevention efforts.

Abacavir in individuals who are pregnant

Although most guidelines no longer recommend abacavir as a preferred option for adults with HIV, HHS guidelines continue to endorse its use in individuals who are pregnant as part of a preferred ART regimen, typically in combination with dolutegravir and lamivudine.⁵⁵ However, this recommendation applies only to those who are HLA-B*5701 negative and do not have chronic HBV coinfection, further complicating its utility in rapid-start scenarios that are often critical during pregnancy. Conversely, EACS, World Health Organization (WHO), and several national guidelines from LMICs prioritize tenofovir-based regimens over abacavir due to their broader availability, superior safety profile, and lack of screening requirements.^49,56,57

Abacavir was previously classified by the FDA as pregnancy category C, based on animal studies indicating adverse effects on the fetus and limited human data. With the availability of safer and more practical alternatives, the role of abacavir in pregnancy is becoming increasingly limited.

Follow-up to the brief case

This case highlights a critical consideration in the long-term management of virologically suppressed individuals with HIV on abacavir-containing regimens. Despite 5 years of stable suppression on abacavir/lamivudine/dolutegravir and the absence of overt cardiovascular disease in this woman in her early 40s, her borderline 10-year ASCVD risk score (5%) prompted a proactive change in her ART.

The decision to switch her to dolutegravir/lamivudine, thereby discontinuing abacavir, demonstrates the evolving understanding of the potential long-term cardiovascular risks associated with this NRTI. While the absolute risk for an individual may be low, even a borderline risk score, in the context of ongoing exposure to a potentially contributing factor, warrants careful consideration and a proactive approach to risk mitigation. The initiation of atorvastatin 20 mg daily for primary ASCVD prevention further demonstrates a comprehensive approach to managing her cardiovascular risk.

This case supports the growing consensus that patients with well-controlled HIV on abacavir-containing ART should be switched to non-abacavir-containing regimens, particularly when cardiovascular risk factors are present or emerging. The availability of highly effective and well-tolerated alternative regimens, such as those based on tenofovir (TDF or TAF) or dual therapies like dolutegravir/lamivudine (as implemented in this case), allows for the maintenance of virologic suppression while potentially mitigating long-term cardiovascular risk.

This case reinforces the need for clinicians to remain vigilant about potential long-term toxicities of ART and to individualize treatment strategies based on a holistic assessment of each patient's virologic control, comorbidities, and risk factors. Given the potential association of abacavir with increased cardiovascular risk and the availability of safe and effective alternatives, a proactive strategy of transitioning virologically suppressed patients off abacavir, particularly those with any cardiovascular risk factors, should be prioritized.

Conclusion

The extensive body of evidence surrounding abacavir necessitates a critical reassessment of its continued use in adult PWH. The well-established association between abacavir use and increased cardiovascular risk, combined with the availability of safer and equally effective alternatives, leaves little justification for its inclusion in modern ART regimens. Indeed, there are virtually no clinical scenarios where abacavir remains indispensable. As the landscape of modern ART continues to evolve, the continued use of abacavir in adult PWH appears increasingly untenable. This shift reinforces the critical necessity of prioritizing ART regimens that achieve robust virologic suppression while minimizing long-term cardiovascular risk, ensuring optimal health outcomes for PWH.

Footnotes

Acknowledgements

None.

Declarations

ORCID iDs

David B. Cluck

Daniel B. Chastain

Diego Cecchini

Andrés F. Henao-Martínez

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Global “expiration” of abacavir in adults with HIV: a rapid review of safety and efficacy concerns challenging its role in modern ART

Abstract

Keywords

The intersection of HIV and cardiovascular disease

Abacavir: Historical context and evolving clinical utility

Reconsidering abacavir initiation in adults with HIV

Presentation of a brief case

Clinical evidence elucidating the complicated role of abacavir-containing ART

Proposed mechanisms of cardiovascular toxicity associated with abacavir

Clinical evidence of cardiovascular disease in PWH treated with abacavir

Follow-up to the brief case

Modern role of abacavir in ART and strategies for transition

Presentation of a brief case

Abacavir in modern ART

Evidence supporting the transition away from abacavir

Abacavir in individuals who are pregnant

Follow-up to the brief case

Conclusion

Footnotes

Acknowledgements

Declarations

ORCID iDs

References