Approaches to the Management of Virologic Failure on Dolutegravir-Based Antiretroviral Therapy in the 50 Countries With the Highest Adult HIV Prevalence

Abstract

Expanded access to dolutegravir as part of a fixed-dose combination with tenofovir disoproxil fumarate and lamivudine (TLD) has revolutionized global human immunodeficiency virus (HIV) treatment, with more than 25 million people prescribed this regimen in 2024. We reviewed national clinical guidelines for management of virologic failure on first-line TLD in the 50 countries with the highest prevalence of HIV among adults; recent guidelines were not available online for four. Among the remaining 46 country guidelines, we identified four distinct approaches: (1) empiric switch to a protease inhibitor (PI)-based regimen without genotypic resistance testing (GRT) (n = 28; 61%); (2) GRT to guide antiretroviral therapy selection (n = 14; 30%); (3) continuation of TLD without GRT (n = 3; 7%); and (4) empiric switch to a PI-based regimen with concurrent GRT (n = 1; 2%). The diversity of guideline-endorsed approaches underscores the critical need for additional data to inform policy regarding this important clinical scenario.

Most people with HIV worldwide are currently prescribed tenofovir/lamivudine/dolutegravir (TLD). We reviewed national guidelines for the management of virologic failure on TLD and identified four distinct approaches. Additional evidence is needed to inform updated policies.

Since 2018, access to integrase strand transfer inhibitors (INSTIs) for HIV treatment has rapidly expanded worldwide with the availability of a generic fixed-dose combination of tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD). The World Health Organization (WHO) recommends TLD as the preferred antiretroviral therapy (ART) regimen for adults and adolescents worldwide, regardless of gender, family planning considerations, or coinfection with hepatitis B virus [1, 2]. As of early 2024, more than 25 million people with human immunodeficiency virus (PWH) were being prescribed dolutegravir-based ART, making TLD the most widely used regimen globally [3]. As several clinical trials have shown that TLD remains effective in the setting of mutations that confer resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs), TLD is also recommended as a second-line regimen in many settings [4–6].

The WHO defines virologic failure (VF) as two consecutive HIV viral load measurements ≥1000 copies/mL with 3 months of interval adherence support between measurements [7]. Although VF among PWH taking TLD is less common than among people taking NNRTI-based ART, VF has been reported among people on TLD for a range of reasons, including incomplete adherence, drug–drug interactions, and/or drug resistance mutations [8]. Recent cohort studies from settings with high HIV prevalence have reported that between 0.6% and 3.2% of participants switched from NNRTI-based regimens to TLD were virologically nonsuppressed through 1 year of follow-up [9–15]. Most instances of VF on first-line TLD are likely related to incomplete adherence alone, as many participants in the aforementioned studies later achieved resuppression; adherence support strategies and improved treatment literacy are needed to improve viral suppression for this group.

Still, despite the drug's high genetic barrier to resistance, treatment-emergent resistance to dolutegravir has been increasingly observed in studies among populations of PWH with VF on TLD [3, 5, 16–18]. A recent review of clinical trials found that ≤0.1% of ART-naive pediatric and adult participants initiated on TLD and ART-experienced participants who were virologically suppressed at switch to dolutegravir-based ART had emergent dolutegravir resistance mutations [17]. This proportion rose to 1.5% among participants with prior VF on NNRTI-based regimens, although prior VF may be inconsistently documented, especially in resource-limited settings [17].

Subsequent surveillance reports have indicated that real-world levels of resistance may be higher, with cross-sectional studies reporting mutations associated with dolutegravir resistance among 3.9%–22.0% of nonsuppressed individuals with successful genotypic resistance testing (GRT) [3, 14, 19]. Notably, these data precede the local introduction of long-acting cabotegravir for HIV preexposure prophylaxis or treatment.

In high-income countries, GRT guides regimen choice when VF is first diagnosed; in the absence of INSTI resistance, individuals are usually continued on their current regimen and provided adherence support. The detection of INSTI resistance by GRT usually prompts switching to an appropriate individualized regimen inclusive of a boosted protease inhibitor (PI) [20–22]. To improve treatment outcomes, GRT results must be reliable, timely, and acted upon by clinicians. However, many countries with high HIV prevalence, where a large proportion of people prescribed dolutegravir-based ART live, do not currently use GRT to guide ART regimen selection for VF on first-line TLD [7]. Commodity and capital cost challenges have limited wide scale-up of routine GRT, which recent global health funding cuts may exacerbate [23, 24]. In this setting, we sought to review national guidelines and describe the current policy landscape related to management strategies for VF on first-line TLD.

REVIEW OF NATIONAL GUIDELINES

Search and Categorization

We reviewed publicly available national HIV treatment guidelines published by governmental health authorities in the 50 countries with the highest adult HIV prevalence [25]. Complete citations are listed in the Supplementary Appendix. Guideline documents were obtained by searching the websites of each country's Ministry of Health, development partners, and global health policy organizations. Approaches to the management of VF on first-line TLD (defined as individuals without known history of previous VF) were categorized into four prespecified groups based on knowledge of typical strategies: empiric switch to a PI-based ART regimen without GRT, GRT to guide ART selection, continuation of TLD without GRT, and other. Two authors (C. T. N. and L. S. J.) independently reviewed each document and categorized each country's approach to VF on first-line TLD as of 1 August 2024. Eight initial discrepancies were reviewed with the senior author (S. M. M.), and the full text of the guideline document in question was reviewed to make a unanimous final determination.

Data Summarization

Our review confirmed a total of four distinct approaches to the management of VF on first-line TLD. We were unable to find recently published guidelines online or peer-reviewed sources referencing the current national approach for management of VF on first-line TLD for the Bahamas, Barbados, Gambia, and Guinea-Bissau (n = 4; 8%). Guidelines for the remaining 46 countries were classified as follows: (1) empiric switch to a PI-based ART regimen without GRT (n = 28; 61%); (2) GRT to guide ART selection (n = 14; 30%); (3) continuation of TLD without GRT (n = 3; 7%); and (4) other: empiric switch to PI-based ART with concurrent GRT followed by subsequent regimen change if indicated by GRT results (n = 1; 2%) (Figure 1). The 50 countries included in our review are listed in Table 1 in order of adult HIV prevalence according to UNAIDS alongside World Bank income grouping, the publication year of the Ministry of Health's most recent publicly available ART guideline, and the clinical approach recommended in that guideline.

Figure 1.

Approaches to the management of virologic failure on first-line TLD in the 50 countries with the highest adult HIV prevalence per national guidelines as of 1 August 2024. Abbreviations: ART, antiretroviral therapy; GRT, genotypic resistance testing; HIV, human immunodeficiency virus; PI, protease inhibitor; TLD, tenofovir disoproxil fumarate + lamivudine + dolutegravir.

Table 1.

Approaches to the Management of Virologic Failure on First-Line TLD in the 50 Countries With the Highest Adult HIV Prevalence Per UNAIDS

Country	Adult HIV Prevalence (%, 15–49 y)	World Bank Income Group	Year of ART Guideline Update	Approach to Virologic Failure on First-Line TLD
Mozambique	11.6	Low	2023	1
Zimbabwe	11.0	Lower middle	2022	1
Equatorial Guinea	6.7	Upper middle	2019a	1
Tanzania	4.3	Lower middle	2019	1
Republic of Congo	4.1	Lower middle	2023	1
Central African Republic	3.4	Low	2018	1
Gabon	2.9	Upper middle	2014	1
Cameroon	2.6	Lower middle	2021	1
Rwanda	2.3	Low	2022	1
South Sudan	1.9	Low	2017	1
Côte d'Ivoire	1.8	Lower middle	2019	1
Haiti	1.7	Lower middle	2016	1
Ghana	1.7	Lower middle	2022	1
Suriname	1.6	Upper middle	2018	1
Guyana	1.5	High	2010	1
Guinea	1.4	Lower middle	2020	1
Nigeria	1.4	Lower middle	2020	1
Sierra Leone	1.4	Low	2020	1
Trinidad and Tobago	1.0	High	2019b	1
Chad	1.0	Low	2019	1
Papua New Guinea	1.0	Lower middle	2019	1
Ukraine	0.9	Lower middle	2022	1
Cabo Verde	0.9	Lower middle	2017	1
Myanmar	0.9	Lower middle	2019	1
Burundi	0.9	Lower middle	2020	1
Mali	0.9	Low	2020	1
Moldova	0.9	Upper middle	2018	1
Ethiopia	0.8	Low	2022	1
Eswatini	25.9	Lower middle	2022	2
Botswana	16.4	Upper middle	2023	2
Malawi	7.1	Low	2022	2
Uganda	5.1	Low	2022	2
Kenya	3.7	Lower middle	2022	2
Togo	1.7	Low	2019	2
Angola	1.5	Lower middle	2015	2
Jamaica	1.3	Upper middle	2017	2
Belize	1.3	Upper middle	2021	2
Thailand	1.1	Upper middle	2022	2
Dominican Republic	1.0	Upper middle	2021	2
Liberia	1.0	Low	2022	2
Panama	1.0	High	2023	2
Russia	0.9c	Upper middle	2020	2
Lesotho	19.3	Lower middle	2022	3
South Africa	17.8	Upper middle	2023	3
Namibia	11.0	Upper middle	2021	3
Zambia	10.8	Lower middle	2022	4
Guinea-Bissau	2.4	Low	—	N/A
Gambia	1.4	Low	—	N/A
Barbados	1.0	High	—	N/A
Bahamas	0.9	High	—	N/A

Recommendations in National Ministry of Health Guidelines as of 1 August 2024.

Recommendations: 1, empiric switch to PI-based second-line ART regimen; 2, GRT to guide ART regimen selection; 3, continue TLD without GRT; 4, empiric switch to PI-based second-line ART regimen with concurrent GRT; N/A, guideline not available online.

Abbreviations: ART, antiretroviral therapy; GRT, genotypic resistance testing; HIV, human immunodeficiency virus; PI, protease inhibitor; TLD, tenofovir disoproxil fumarate + lamivudine + dolutegravir.

^aAn updated ART guideline published by the Equatorial Guinea MOH was not available online as of 1 August 2024. However, a 2022 journal article by HIV researchers working in Equatorial Guinea references national guidelines published in 2019 that recommend approach 1 (empiric switch to PI-based second-line ART): Rodríguez-Galet et al [26].

^bAn updated ART guideline published by the Trinidad and Tobago MOH was not available online as of 1 August 2024. However, a 2024 journal article by HIV researchers working in Trinidad and Tobago cited references national guidelines published in 2019 that recommend approach 1 (empiric switch to PI-based second-line ART): Gbadamosi et al [27].

^cEstimates for adult HIV prevalence in Russia are not available via UNAIDS as of 1 August 2024. However, a recent peer-reviewed article cites a general population prevalence of 0.9% (including all age ranges) based on estimates from Russian health authorities: Nikoloski et al [28]. Russian Federal Scientific and Methodological Center for AIDS Prevention and Control. HIV infection in the Russian Federation as of 31 December 2021. No longer online.

Approach 1: Empiric Switch to Protease Inhibitor–based Antiretroviral Therapy Without Genotypic Resistance Testing

The most common approach to the clinical management of VF on first-line TLD in the published guidelines was the strategy recommended by the 2013, 2016, and 2021 WHO HIV treatment guidelines: empiric switch from the first-line regimen to PI-based second-line ART without use of GRT [7]. Among the 46 countries with the highest adult HIV prevalence and guidelines available for review, 28 (61%), including 20 in Africa, three in South America, two in Asia, two in Europe, and one in North America, utilize this approach. While some of the national programs in this group recommend GRT for PWH experiencing VF on second-line or third-line regimens, GRT is not currently recommended for VF on first-line TLD.

Of these 28 countries, 22 (79%) last updated their guidelines prior to the WHO's latest 2021 HIV guidelines, and seven (25%) have not updated their guidelines since the WHO's 2018 global endorsement of TLD use for all adults. One country, Rwanda, included “specialist consultation and genotyping” as an alternative approach for PWH experiencing VF on dolutegravir-based regimens in its 2022 guidelines, although the primary recommendation remained empiric switch to a PI-based regimen without GRT [29].

Approach 2: Genotypic Resistance Testing to Guide Antiretroviral Therapy Selection

In contrast to the empiric switch strategy, some government health agencies now recommend GRT to guide ART selection. Among the 46 high-prevalence countries in our review, 14 (30%), including eight in Africa, four in North America, and two in Asia, recommended GRT at the time of VF on first-line TLD. Ten of these 14 countries (71%) had last updated their guidelines in 2021 or later, while two (14%) have not updated their guidelines since the WHO's 2018 endorsement of TLD use for all PWH.

Language in Malawi's 2022 HIV guidelines is representative of this approach: “Patients on dolutegravir- and PI-based regimens who don't re-suppress below 1000 copies/mL after an initial high viral load despite good adherence need a genotype sample for resistance testing… to confirm the presence of drug-resistant virus before switching to second- or third-line ART” [30].

Most countries in this group recommend GRT at VF using the WHO definition of VF described previously. One notable exception is Botswana, where the Ministry of Health's 2023 HIV guidelines recommend a 30-day period of directly observed therapy on TLD after two viral load measurements >200 copies/mL without at least a one-log decline in VL in the interim, followed by GRT if the viral load is persistently elevated >200 copies/mL after the period of directly observed therapy [31].

Approach 3: Continue Tenofovir, Lamivudine, and Dolutegravir

Guidelines for three countries with adult HIV prevalence ≥11.0%, Namibia, Lesotho, and South Africa, recommend long-term continuation of first-line TLD in the setting of VF without either GRT or empiric switch to PI-based ART [32–34 ]. Namibia's 2021 HIV guidelines recommend continuation of TLD at VF for at least one full year and then empiric switch to a PI-based regimen if the viral load remains elevated [32]. Lesotho's 2022 HIV guidelines require an individual take TLD for at least two full years prior to consideration of GRT at VF unless there is documented prior VF on an earlier INSTI-based regimen, documented NRTI resistance from prior GRT, known exposure to HIV preexposure prophylaxis at the time of HIV acquisition, or a documented drug–drug interaction [33].

South Africa's 2023 HIV guidelines state that “as a rule, resistance testing is not indicated for clients on TLD1 [first-line TLD].” Listed exceptions to this rule for adult PWH include concern for prior VF on a prior regimen before transition to TLD (“'incorrect classification as TLD1”) and a recent prolonged drug–drug interaction between once-daily dolutegravir and a rifamycin, certain antiepileptics, or divalent cation supplements [34]. Clinicians are advised to attempt objective assessment of adherence to TLD by reviewing clinic attendance and pharmacy records or by performing a pharmacologic assessment of blood or urine drug levels of a component of TLD if a validated assay is available. However, there is no explicit guidance beyond “discussion with an expert” for scenarios where an individual remains nonsuppressed on first-line TLD and where a pharmacologic assessment indicates adherence levels that should facilitate re-suppression in the absence of resistance to dolutegravir.

Approach 4: Empiric Switch to Protease Inhibitor–based Antiretroviral Therapy With Concurrent Genotypic Resistance Testing

As a fourth approach, Zambia's 2022 HIV guidelines recommend that PWH diagnosed with VF on first-line TLD undergo GRT and that their ART should immediately be changed from TLD to a darunavir-based second-line regimen:

“HIV genotype resistance testing will be done on all patients after treatment failure who have completed enhanced adherence counseling with a repeat [elevated] viral load…. Patients failing first-line treatment must be switched to the standard second-line according to the guidelines without waiting for the genotype results. The second-line regimen can be modified once the genotype results are out…. Darunavir/ritonavir is recommended for use by patients failing first-line dolutegravir-based regimens” [35].

Recency of Update and Recommendation for Genotypic Resistance Testing

Associations between guideline recency and recommendation for GRT at VF on TLD were evaluated by χ² test. Countries that published their latest HIV guidelines in 2020 or earlier were less likely to recommend GRT at VF on TLD (P = .02) (Figure 2).

Figure 2.

Evolution of recommended approaches to management of virologic failure on first-line TLD by year of most recent published national HIV guidelines. Abbreviations: ART, antiretroviral therapy; GRT, genotypic resistance testing; HIV, human immunodeficiency virus; PI, protease inhibitor; TLD, tenofovir disoproxil fumarate + lamivudine + dolutegravir.

DISCUSSION

A heterogeneous global policy landscape guides management of VF among PWH who are on TLD for first-line ART. The longstanding WHO-recommended strategy of empiric switch to PI-based second-line ART without GRT remains most common, but an increasing number of national programs are opting for different approaches, particularly among countries that have updated their guidelines more recently.

Considerations and Tradeoffs for Each Approach

Each of the four identified strategies reflects national assessments of key considerations and tradeoffs (Table 2). The WHO-recommended algorithm employed for Approach 1 prioritizes discontinuation of failing regimens, relying on persistent viral nonsuppression as a proxy for drug resistance in the absence of GRT, and assumes an increased likelihood of virologic suppression on a PI-based regimen at VF on first-line ART [7]. This approach was developed in the era when NNRTI-based ART regimens with low barriers to resistance were the only first-line regimens available in most low- and middle-income countries. It was supported by surveillance studies showing high proportions of NNRTI resistance at the time of VF, by trials demonstrating lack of benefit from the addition of GRT at VF on NNRTI-based ART, and by studies demonstrating preservation of ART effectiveness with PI-based empiric second-line regimens containing NRTIs [5, 36–38 ]. However, the 2021 WHO guidelines state that “the role of drug resistance testing is unclear in a treatment failure algorithm for PWH receiving dolutegravir-based treatment,” citing this as an important research gap for which additional data are needed [7]. As new evidence emerges, the WHO may update its treatment guidelines and recommendations.

Table 2.

Descriptions of Four Approaches to the Management of Virologic Failure on First-Line TLD

Approach	Rationale	Advantages	Disadvantages	Proportion of Countries Using This Approacha
1. Empiric switch to PI-based second-line regimen	Avoid continuation of failing regimen where GRT is not available; avoid costs of GRT	PWH with unconfirmed INSTI resistance and underlying VF are changed to PI-based second-line therapy and are likely to re-suppress with adequate adherence	PWH with incomplete adherence and no INSTI resistance face higher pill burden and possibility of more adverse effects on more expensive PI-based ART, potentially adding new adherence challenges	28/46 (61%)
2. GRT to guide regimen selection	Optimize individual treatment outcomes	When present, INSTI resistance is detected, and the ART regimen can be individualized. When absent, interventions to promote adherence to TLD can be prioritized	Costs and complexity of incorporating and maintaining GRT as part of a public health approach to HIV treatment monitoring	14/46 (30%)
3. Continue TLD without GRT	Avoid unnecessary switch to PI-based regimen (assumes low prevalence of INSTI resistance among PWH with VF on first-line TLD, and acknowledges data gaps on clinical significance of some integrase mutations); avoid costs of GRT	PWH with incomplete adherence and no INSTI resistance are continued on a simple and effective regimen, and are likely to resuppress with improved adherence, while PIs are reserved for those with a high likelihood of INSTI resistance	PWH with undetected INSTI resistance underlying VF are continued on a failing regimen, with possible individual risks of poor clinical outcome and public health implications of potential transmitted resistance	3/46 (7%)
4. Empiric switch to PI-based second-line regimen with concurrent GRT	Balance rapid transition to effective second-line regimen for PWH with INSTI resistance underlying VF while returning to ease of TLD if GRT demonstrates no INSTI resistance	PWH with INSTI resistance underlying VF are changed to PI-based second-line therapy earlier than in approach 3, and are likely to re-suppress with adequate adherence	PWH with incomplete adherence and no INSTI resistance face higher pill burden and possibility of more adverse effects on PI-based ART, then later changed back to TLD after GRT results are available, introducing potential confusion	1/46 (2%)

Abbreviations: ART, antiretroviral therapy; GRT, genotypic resistance testing; HIV, immunodeficiency virus; INSTI, integrase strand transfer inhibitors; PI, protease inhibitor; PWH, people with human immunodeficiency virus; TLD, tenofovir disoproxil fumarate + lamivudine + dolutegravir; VF, virologic failure.

^aAmong the 50 countries with the highest adult HIV prevalence that were included in this review, national HIV treatment guidelines were not available online for four.

Approach 2, which involves GRT at diagnosis of VF on first-line TLD to guide subsequent regimen selection, prioritizes optimizing individual clinical outcomes, although it requires investments in health systems to incorporate and maintain GRT as part of an HIV treatment monitoring algorithm, as well as to support clinicians attempting to interpret and act upon GRT results. Meaningful clinical action also requires the availability of additional classes of antiretrovirals for inclusion in second-line or salvage regimens. Prior to global health funding reductions in 2025, most countries updating their guidelines after 2020 were incorporating GRT.

Several forthcoming developments may help to address barriers to expanding access to GRT in low- and middle-income countries. Costs of implementing GRT for routine HIV care in resource-limited settings may decrease with adoption of advance market commitments, pooled procurement mechanisms, and implementation of programmatic strategies regarding use of stored remnant viral load samples for reflex GRT among eligible PWH, and if lower-cost near point-of-care GRT assays advance in development [23, 39–43]. Novel adherence monitoring tools such as a point-of-care urine tenofovir lateral flow assay or laboratory-based drug level testing may also enable more targeted use of GRT among PWH most likely to have INSTI resistance. Objective evidence of recent exposure to TLD in the setting of VF may suggest that resistance to INSTIs and/or NRTIs in the setting of selective drug pressure, rather than incomplete adherence alone, underlies VF [44].

Approach 3, which entails continuation of TLD without GRT at VF on first-line TLD, represents a modified public health approach that prioritizes avoidance of unnecessary switches to PI-based second-line ART, and assumes a low proportion of INSTI resistance underlies VF. The full text of the guidelines for South Africa, Lesotho, and Namibia, which inform the care of nearly one-quarter of all PWH, indicates three primary considerations underlie the strategy to continue TLD for those with first-line TLD failure [25, 32–34]. First, acquired INSTI resistance was expected to be less likely than NNRTI resistance, particularly for those on first-line TLD, given dolutegravir's high genetic barrier to resistance. Lesotho's 2022 HIV guidelines state that:

“To date, less than five cases of dolutegravir resistance have been described [when dolutegravir is paired with at least one active NRTI in INSTI-naïve patients]. Thus, although a high viral load has traditionally been a marker of possible resistance, this paradigm no longer applies for the most part in patients receiving a dolutegravir-based regimen… [and] should not be assumed to reflect possible resistance. Rather, it can be assumed that the detectable viral load represents poor adherence” [33].

Second, this strategy elevates concerns about the potential harms of an unnecessary empiric switch to PI-based ART, including greater pill burden with higher risk of adverse effects, more frequent drug–drug interactions, and higher costs. While darunavir is a more effective and better-tolerated PI than atazanavir and lopinavir, this agent is not yet widely available in most low- and middle-income countries [6, 39 ].

Thirdly, GRT is costly to implement at scale, particularly compared with the $45 per person per year cost for TLD itself [24, 45, 46]. As an example, Namibia's 2021 HIV guidelines state that “although management of patients would be easier if resistance testing was done prior to selection of a second-line regimen, this is costly and should not be done routinely” [32].

Lastly, Approach 4 in Zambia illustrates the challenges in reconciling the tradeoffs described above, balancing the complexities of multiple treatment switches for the same person against the desire to avoid continuing failing regimens. Notably, Zambia's inclusion of ritonavir-boosted darunavir (separate tablets as of 2024) as the recommended PI for second-line regimens in its guidelines may render second-line regimens more tolerable there than in countries recommending ritonavir-boosted atazanavir or lopinavir [35].

Evaluating Strategies for Addressing Virologic Failure on Tenofovir/Lamivudine/Dolutegravir

The evolving policy landscape and current diversity of approaches signal that outcome data are needed to guide decision-making regarding the most effective, sustainable, and cost-effective strategy for managing VF on TLD in each setting. Clinical trials and prospective cohort studies investigating this topic are challenging to design and conduct, as dolutegravir resistance is currently relatively rare, though disruptions in routine HIV care caused by funding cuts initiated in 2025 may imperil consistent access to TLD for many individuals and raise the incidence of VF and acquired INSTI resistance in many countries. At least three studies are currently underway to evaluate the efficacy of GRT, point-of-care pharmacologic adherence measures, and other tools in this setting.

For example, the RESOLVE study, a randomized clinical trial in South Africa and Uganda, compares three clinical approaches: national standard of care, individualized management guided by GRT and urine tenofovir screening, and immediate switch to a PI-based regimen without GRT [47]. The Ndovu study, a multinational cohort study, follows nonsuppressed PWH on TLD with an embedded randomized clinical trial to evaluate continuation of TLD vs switch to a darunavir-based regimen for those with at least one major INSTI resistance mutation [48]. In addition, the DTG RESIST study, nested within the International epidemiology Databases to Evaluate AIDS (IeDEA) collaboration, is enrolling PWH with VF on TLD and other dolutegravir-based ART regimens in 17 countries across four continents to identify factors associated with emergent INSTI resistance [49].

Limitations

An important limitation of our review is that the most recent update to guidelines published online by seven countries preceded the 2018 WHO endorsement of TLD use for all adults; we assumed that older guidelines are still in effect in the TLD era and did not directly contact Ministries of Health to verify that guideline documents available online reflected the version currently in use.

Summary and Conclusions

There is currently broad variability in the management of VF among PWH receiving TLD across countries with a high prevalence of HIV. A data-driven approach in the era of universal access to integrase inhibitors is warranted to advance the complementary public health and clinical goals of protecting the durability of TLD and optimizing individual treatment outcomes in an era beset for funding cuts. Evidence from ongoing studies is needed to fill critical research gaps and help inform updated policy recommendations and investments in the next phase of the global HIV response.

Supplementary Data

Supplementary materials are available at Clinical Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.