Dolutegravir

HIV integrase inhibitor (strand transfer inhibitor)

Also sold as Tivicay, Tivicay PD.

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Findings for this medication

Research about this medication, graded for how strongly each finding can be attributed to it. Nothing here describes your own levels.

Dolutegravir has almost no classical depletion machinery. It is cleared mainly by glucuronidation (UGT1A1, with some CYP3A), did not inhibit the CYP enzymes tested in vitro (IC50 above 50 micromol/L) and did not induce CYP1A2, CYP2B6 or CYP3A4 in vitro; 53% of an oral dose is recovered unchanged in feces and less than 1% is excreted unchanged in urine [1]. The one mechanism with a measured human effect runs in the opposite direction to depletion: polyvalent cations (calcium, iron, magnesium, aluminum, and the metals in cation-containing antacids and laxatives) lower dolutegravir absorption when swallowed together on an empty stomach. In the label's single-dose studies, simultaneous calcium carbonate fasted gave an AUC ratio of 0.61 (90% CI 0.47 to 0.80) and ferrous fumarate fasted 0.46 (0.38 to 0.56), while taking either with food, or dolutegravir 2 hours before the iron, left exposure unchanged [2][3]. Under Hard Rule 4 this is a nutrient-to-drug timing interaction, graded yellow at most, and it is not a mineral deficiency.

HIV integrase inhibitor (strand transfer inhibitor) · ATC J05AJ03 (WHO ATC/DDD Index [4]) · also sold as Tivicay and Tivicay PD; in Triumeq and Dovato and Juluca · reviewed 2026-10-09. This describes research about the medication. It does not say anything about your own levels or health.

How to read the evidence grades

These colours describe how strongly a finding can be attributed to the medication in the research. They are not a severity score and they say nothing about your own health.

Grades describe how strongly a finding can be attributed to Dolutegravir in the research — not how common it is, how serious it would be, and not anything about you personally.

Red — Severe: Two or more independent Tier A sources, this drug in the cohort, the nutrient directly measured, consistent direction, clinically meaningful magnitude, a named mechanism, no substantial contradicting Tier A evidence.
Orange — Moderate: At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit.
Yellow — Low: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction.
Not graded — disclosed evidence gap: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result.Source definition: Not gradeable under the rules above because nothing has been measured. Published as a documented gap, never as reassurance that there is no effect.

What the research found

Polyvalent cations (calcium, iron, magnesium, aluminum, zinc): nutrient-to-drug timing interaction, not a depletion

Yellow — Low

Evidence: low (timing)

Direction: nutrient affects the drug (Hard Rule 4). Divalent and trivalent cations taken with dolutegravir on an empty stomach lower dolutegravir exposure; the mineral is not depleted and the interaction is managed by taking the tablet with food or by separation in time.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow, low (timing)

Limits on what this shows

Key null findings: With a meal, calcium carbonate (1.09) and ferrous fumarate (0.98) did not change dolutegravir exposure; dolutegravir given 2 hours before ferrous fumarate left exposure unchanged (0.95) [2][3].
At-risk subgroups: People taking antacids, calcium or iron supplements, or multivitamins while fasting, including those who take dolutegravir at bedtime with a mineral product.
Counter-evidence on record: In zebrafish embryos (Tier B), magnesium partially rescued dolutegravir developmental toxicity and calcium had no effect [9]; this is a nutrient-modifies-drug-toxicity finding in an animal model, not a human depletion finding.

Regulatory status

Table 8: cation-containing antacids or laxatives, sucralfate and buffered medicines, give dolutegravir 2 hours before or 6 hours after. Oral calcium or iron supplements and multivitamins can be taken at the same time with food; under fasting conditions take dolutegravir 2 hours before or 6 hours after [1].

Population evidence

Single 50 mg dolutegravir doses, n = 11 to 16 per condition, geometric mean AUC ratios (90% CI): calcium carbonate 1,200 mg simultaneous fasted 0.61 (0.47 to 0.80), fed 1.09 (0.84 to 1.43) [2]; Maalox simultaneous 0.26 (0.22 to 0.32), 2 hours after dolutegravir 0.74 (0.62 to 0.90) [2]; ferrous fumarate 324 mg simultaneous fasted 0.46 (0.38 to 0.56), fed 0.98 (0.81 to 1.20), 2 hours after dolutegravir 0.95 (0.77 to 1.15) [3]; One-A-Day multivitamin simultaneous 0.67 (0.55 to 0.81) [3]. The iron and multivitamin rows come from the Dovato label table (same dolutegravir component, same single-dose studies as presented there); they were not found in the portion of the Tivicay label read. Magnesium-only, zinc-only and aluminum-only rows were not retrieved; magnesium and aluminum are covered by the antacid row.

Mechanism

Reduced absorption when taken together with polyvalent cations; the label groups these products as cation-containing. The label's own mechanistic sentence was not in the portions read.

Cohort test

Dolutegravir was the drug in every pharmacokinetic study cited here. No study measured mineral status.

Why yellow

The Tier A evidence is strong for the interaction but its direction is nutrient to drug, so Hard Rule 4 caps it at yellow and files it as a timing interaction with a separation interval.

Counter-evidence held on record

Framing caution for the consumer surface Not a mineral deficiency and not a reason to stop calcium, iron or magnesium. The point is timing relative to the dolutegravir dose; ask a pharmacist before changing the schedule.

Folate (circulating folate not lower; receptor antagonism preclinical; neural tube defect is an outcome)

Yellow — Low

Evidence: low

Direction: neutral to reverse. In randomized-trial datasets that included dolutegravir, serum, plasma and red blood cell folate were higher than or similar to comparator regimens. Folate receptor antagonism is shown in binding assays, cell lines and zebrafish, and the neural tube defect signal is a pregnancy outcome, not a folate measurement.

Full detail and limits

Limits on what this shows

Key null findings: No human study retrieved found lower folate or B12 with dolutegravir. In ADVANCE the "rise" is relative to an efavirenz arm in which folate fell, so it is not evidence that dolutegravir raises folate against no treatment [5].
At-risk subgroups: Women around conception and in the first trimester (the label notes missing folic acid use data) [1]. Folate fortification context was not retrieved from an opened source.
Counter-evidence on record: The same preclinical group reports dolutegravir antagonism of the receptor, so a neural tube mechanism has not been excluded by the human circulating-folate data. Mouse studies listed on PubMed by title (PMIDs 37382903, 37586112) and placental transporter work (34954655) were not opened [24].

Regulatory status

Sec 8.1: neural tube defect prevalence with dolutegravir at conception was 0.11% (95% CI 0.05 to 0.19%) in Botswana versus 0.11% (0.07 to 0.16%) with non-dolutegravir regimens and 0.06% (0.05 to 0.08%) in HIV-negative women; in Eswatini 0.08% (0.04 to 0.16%) versus 0.22% (0.06 to 0.56%) and 0.08% (0.06 to 0.12%). A first interim Botswana analysis had identified an association. The surveillance studies lacked data on folic acid use before conception or in the first trimester [1].

Population evidence

ADVANCE substudy, Chandiwana 2021 [5]: 406 women; serum folate change over 12 weeks +4.0 +/- 8.1 nmol/L (tenofovir alafenamide/emtricitabine + dolutegravir), -1.8 +/- 8.9 (tenofovir disoproxil/emtricitabine + dolutegravir), -5.9 +/- 8.1 (efavirenz arm); efavirenz-arm women had low folate at weeks 12 and 24; 26 women who became pregnant: folate rose in both dolutegravir arms, -3.3 +/- 8.1 in efavirenz. ODYSSEY substudy, Barlow-Mosha 2023 [6]: 229 Ugandan children, median age 12.3 years; plasma folate higher on dolutegravir at week 4 (+1.6 ng/mL, 95% CI 0.8 to 2.3) and week 96 or later (+2.7, 1.7 to 3.7); red blood cell folate +73 ng/mL (3 to 143) at week 96 or later; vitamin B12 and mean corpuscular volume did not differ. VESTED, Jacobson 2024 [7]: 340 pregnant women and 310 infants; red blood cell folate at delivery (geometric mean) 830, 743 and 694 nmol/L for dolutegravir + FTC/TAF, dolutegravir + FTC/TDF and efavirenz/FTC/TDF; adjusted maternal trajectory ratios versus efavirenz 1.028 (0.995 to 1.062) and 1.008 (0.975 to 1.042); infant ratios 1.075 (0.932 to 1.240) and 1.055 (0.915 to 1.217); authors: no clinically meaningful differences; at entry 6% were folate deficient (below 305 nmol/L).

Mechanism

Binding assays and a human placental cell line: dolutegravir acts as a noncompetitive (partial) antagonist of folate receptor 1 at therapeutic concentrations; it did not inhibit dihydrofolate reductase; folic acid reduced zebrafish embryo toxicity [8]. Magnesium raised folate binding to purified receptor by 30% in the presence of dolutegravir and partly rescued embryos [9]. No human folate transport measurement was found.

Cohort test

Dolutegravir was in the cohort in [5][6][7]; the ADVANCE and VESTED comparators were efavirenz-based, ODYSSEY compared dolutegravir with standard non-dolutegravir ART.

Why yellow

Tier B mechanistic plausibility plus reverse-direction Tier A findings. No directly measured deficit exists, so orange is not met.

Counter-evidence held on record

Framing caution for the consumer surface Not evidence that dolutegravir lowers folate. A neural tube defect is a birth outcome, not a nutrient deficiency. Folic acid decisions before or during pregnancy belong with the prescriber; no dose is given here.

Vitamin D (25-hydroxyvitamin D fell slightly in both arms; bone density is an outcome)

Yellow — Low

Evidence: low

Direction: neutral to small decrease, not separable from the effect of starting ART. No dolutegravir-specific vitamin D deficit was found; bone mineral density findings are clinical outcomes and are not filed as vitamin D or calcium deficiency.

Full detail and limits

Limits on what this shows

Key null findings: No significant difference in vitamin D change between dolutegravir and efavirenz arms [10]; lumbar spine BMD did not fall [11].
At-risk subgroups: People starting ART with low baseline vitamin D, dark skin or low sun exposure; none stratified in the records read.
Counter-evidence on record: Both arms fell, there was no untreated or non-ART control, and ART initiation, immune recovery, season and efavirenz exposure are competing explanations (Hard Rule 6). Full-text vitamin D data beyond percent change were not available in the PMC article [10].

Regulatory status

No vitamin D statement in the label text read [1].

Population evidence

SINGLE bone substudy, Tebas 2015 [10]: 833 ART-naive adults randomized to dolutegravir + abacavir/lamivudine or efavirenz/emtricitabine/tenofovir disoproxil; percentage change in vitamin D from baseline at weeks 48, 96 and 144: -7%, -5%, -2% (dolutegravir arm) versus -10%, -10%, -4% (efavirenz arm); the authors state no significant difference between arms in vitamin D change (no p-values, absolute values or per-arm n in the record read). Bone turnover markers (CTx, osteocalcin, BSAP, P1NP) rose in both arms and rose significantly less on dolutegravir. SCOLTA real-world cohort, Bonfanti 2020 [11]: 160 people with HIV on dolutegravir; lumbar spine BMD +13.1 mg/cm3 (95% CI 1.7 to 24.6), +1.6% (0.3 to 2.8%) after a median 102 weeks; femoral neck increase not significant. Outcome only; 25-hydroxyvitamin D was not the exposure. ADVANCE [12]: the abstract states bone density effects were less pronounced on dolutegravir regimens than on the efavirenz regimen (figures not in the record read).

Mechanism

None identified for dolutegravir. The label reports no in vitro induction of CYP1A2, CYP2B6 or CYP3A4 [1].

Cohort test

Dolutegravir (with abacavir/lamivudine) was in the cohort in [10]; dolutegravir-containing regimens in [11].

Why yellow

Context flag: a measured small decrease with no drug-specific attribution and no mechanism. Bone density is an outcome entry under Hard Rule 2.

Counter-evidence held on record

Framing caution for the consumer surface Not a finding of vitamin D deficiency caused by dolutegravir. Bone density is not vitamin D status. No supplement recommendation.

Weight gain and metabolic change (clinical outcome, not a nutrient deficiency)

Yellow — Low

Evidence: low (outcome)

Direction: outcome entry, no nutrient measured. Weight gain and lipid change are documented with dolutegravir-containing regimens; they are clinical or metabolic outcomes and are not filed as a deficiency of any nutrient (Hard Rule 2).

Full detail and limits

Limits on what this shows

Counter-evidence on record: Competing explanations the sources read do not exclude: weight recovery after starting any effective ART, and differing weight effects of the efavirenz comparator, so the absolute attribution to dolutegravir is uncertain.

Regulatory status

Sec 6.2 postmarketing: "weight increased." Sec 6.1 includes lipid change tables (Table 7) and Grade 3 to 4 laboratory abnormalities including hyperglycemia under 1% (SPRING-2) [1]. The arm labelling of the Table 7 values was ambiguous in the summarized text, so numbers are not reproduced.

Population evidence

ADVANCE, Venter 2019 [12]: 1,053 treatment-naive adults in South Africa randomized to FTC + dolutegravir with TAF, FTC + dolutegravir with TDF, or TDF-FTC-efavirenz; abstract: weight gain was greatest among women on the TAF-based regimen, mean increase 6.4 kg versus 3.2 kg (TDF-based) and 1.7 kg (standard care); confidence intervals and timepoint-specific values were not in the record read (the report covers 48-week data).

Mechanism

Not defined in the sources read. A cross-sectional microbiome study links weight change on dolutegravir or bictegravir to specific taxa (see Gut microbiome risk) [23].

Cohort test

Dolutegravir was in the cohort in [12].

Why yellow

Outcome entry. Printed so a reader does not mistake weight change for a nutrient signal.

Counter-evidence held on record

Framing caution for the consumer surface A clinical outcome. It does not show that any vitamin or mineral is low and is not a basis for supplementation.

The five body-system areas

Each finding is counted once, in a single area. Where a study is mentioned in a second area it is context only.

Mitochondrial Burden

Each finding below is counted once, in this area only.

Mitochondrial burden (reversible in vitro stress; human adipose respiration not lower)

Yellow — Low

Evidence: low

Direction: mixed, drug toxicity pathway rather than a nutrient deficiency. Dolutegravir-containing regimens raised mitochondrial ROS, mass and fragmentation in cultured human cells and reversed on washout; one human adipose-tissue study found complex I respiration higher, not lower, in women on tenofovir/lamivudine/dolutegravir.

Full detail and limits

Limits on what this shows

Counter-evidence on record: The human study found higher respiration and has no HIV-positive untreated or non-dolutegravir comparator; the cell work cannot attribute effects to dolutegravir alone.

Regulatory status

No mitochondrial statement in the label text read; sections 12.4 and 13 were not read [1].

Population evidence

Ajaykumar 2023 [13]: WI-38 fibroblasts (with and without hTERT) and PBMC exposed to 7 regimens (3 containing dolutegravir) for 9 days, then 6 days off drug; dolutegravir-containing regimens increased apoptosis, mitochondrial ROS and mitochondrial mass and fragmented mitochondrial networks more than a raltegravir regimen; fully reversible. Single-drug contrasts and concentrations were not in the record read. Madlala 2025 [14]: 67 pregnant women with HIV on tenofovir/lamivudine/dolutegravir and 31 HIV-negative women; gluteal adipose biopsies at first and third trimester; at third trimester HIV infection was associated with higher complex I-linked respiration (beta 0.13, P = 0.02), stronger in those on the regimen 6 months or less (beta 0.16, P = 0.02). HIV status and regimen are not separable.

Mechanism

No nutrient mechanism. Stress phenotype in vitro only; in vivo direction not lower respiration [14].

Cohort test

Dolutegravir was in the exposure of [13] (as part of three regimens) and in the cohort of [14] (as a fixed three-drug regimen).

Why yellow

Tier B in vitro plus one human study with mixed direction.

Counter-evidence held on record

Framing caution for the consumer surface Not evidence of mitochondrial damage in people, and not a reason to take mitochondrial supplements.

Oxidative Stress

Each finding below is counted once, in this area only.

Oxidative stress (in vitro ROS rise; no clinical antioxidant marker shown to move)

Yellow — Low

Evidence: low

Direction: drug-associated ROS rise in vitro; in people, the one study retrieved links redox markers to dolutegravir concentration rather than showing dolutegravir changing them. No antioxidant nutrient depletion measured.

Full detail and limits

Limits on what this shows

Counter-evidence on record: No malondialdehyde, glutathione or antioxidant enzyme comparison of dolutegravir users with a matched control was found. A PubMed listing also shows N-acetylcysteine and antiretroviral microglial activation work (PMID 33013619) that was not opened [24].

Regulatory status

No oxidative stress statement in the label text read [1].

Population evidence

Ajaykumar 2023 [13]: mitochondrial ROS rose with dolutegravir-containing regimens in fibroblasts and PBMC. Bhuyan 2016 [17]: DCFDA fluorescence (ROS) rose at 19.1 micromol/L in erythrocytes. Cusato 2025 [16]: 30 people with HIV assessed on triple therapy and 6 months after switching to dolutegravir-containing dual therapy; plasma dolutegravir correlated with cytoplasmic N-acetylcysteine (S = -0.419, p = 0.033) and with white blood cells (S = 0.480, p = 0.011); the question was whether oxidative stress affects dolutegravir concentrations, so the direction is redox to drug.

Mechanism

ROS generation from mitochondria and erythrocyte calcium and ceramide signaling in vitro [13][17].

Cohort test

Dolutegravir was in the exposure in [13][17] and the cohort in [16].

Why yellow

Tier B only for causation; the human study does not show the drug moving a redox marker.

Counter-evidence held on record

Framing caution for the consumer surface Not evidence of antioxidant depletion and not a reason to take antioxidants.

Copper and Iron Balance

Copper and iron are assessed separately. Nothing here is counted twice.

Iron (iron rose and ferritin fell after start; no deficit shown)

Yellow — Low

Evidence: low

Direction: neutral to reverse. In a prospective cohort starting dolutegravir, serum iron rose and ferritin and C-reactive protein fell by 6 months. Rare sideroblastic anemia is a labeled outcome, not an iron-status finding.

Full detail and limits

Limits on what this shows

Counter-evidence on record: No comparator ART and no untreated arm (Hard Rule 6): the change tracks control of HIV and inflammation. Baseline iron and ferritin differed by co-infection status in the same cohort [18].

Regulatory status

No iron indices in the label text read; sideroblastic anemia is listed under postmarketing events [1][2]. Separate timing interaction with oral iron: see the polyvalent cation entry.

Population evidence

Kamurai 2024, Harare [18]: 100 people with HIV (51 women) starting or restarting dolutegravir-based ART, prospective, iron, ferritin and C-reactive protein at baseline and 6 months; at baseline those with co-infections had higher ferritin and CRP and lower iron (P below 0.001); at 6 months CRP and ferritin decreased and iron increased regardless of co-infection; numeric values and 6-month p-values were not in the record read.

Mechanism

None named. The direction is consistent with resolution of inflammation as viral load falls.

Cohort test

All participants started dolutegravir-based ART; the regimen partners were not given in the record read.

Why yellow

Tier B case-level plausibility via the labeled sideroblastic anemia, with Tier A data showing no deficit. Not ungraded because sources exist; not orange because no deficit was measured.

Counter-evidence held on record

Framing caution for the consumer surface Not a finding of iron deficiency or iron overload from dolutegravir. No iron supplement recommendation.

Copper

Not graded — disclosed evidence gap

See study details

No copper measurement or copper claim was found for dolutegravir.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

Why no grade: Both conditions of the dual test hold: no Tier B or C evidence for copper was found for this drug or for integrase inhibitors, and no circulating claim was found to rebut as white. This is a disclosed evidence gap, not a finding of safety.

Channels tried

(1) Tivicay and Dovato label text via DailyMed and Drugs.com (summarizing fetch tools): no copper statement in the portions read (sections 12.4 and 13 and the end of the Tivicay page were not read). (2) PubMed listing "dolutegravir copper": a result page of zero records marked invalid-form, then a reCAPTCHA page on a retry. (3) PubMed "dolutegravir serum zinc" and "dolutegravir magnesium": zero records, invalid-form. (4) PubMed boolean query with copper, zinc, selenium, magnesium and ceruloplasmin: invalid-form, zero records. (5) PubMed listing dolutegravir with anemia, hemoglobin, ferritin or sideroblastic: 47 results, 15 shown, none about copper. (6) Crossref bibliographic search "dolutegravir serum copper zinc selenium": ten records, none about dolutegravir. (7) Crossref search "dolutegravir copper deficiency ceruloplasmin": eight records, none about dolutegravir. (8) WebSearch: shared budget exhausted for the turn.

Gap type

Probable genuine literature gap with a residual tooling limit: every query that returned records returned nothing specific to dolutegravir and copper, but PubMed searches were throttled or blocked and WebSearch was unavailable, so the gap is not proven. The case reports of sideroblastic anemia [20][21] did not have copper or vitamin B6 values in the text retrieved, which is a reason to re-check this entry when access allows.

Gut Microbiome Risk

Each finding below is counted once, in this area only.

Gut microbiome risk (richness rose versus darunavir; taxa linked to weight gain; reverse or mixed direction)

Yellow — Low

Evidence: low

Direction: reverse or mixed. In a randomized trial in advanced HIV, dolutegravir increased gut microbial richness and diversity relative to ritonavir-boosted darunavir; a cross-sectional study found specific bacterial groups, not overall diversity, associated with weight gain on dolutegravir or bictegravir. No microbiome-linked loss of an endogenously synthesized nutrient was found.

Full detail and limits

Limits on what this shows

Counter-evidence on record: The comparator was an active drug (darunavir/ritonavir), not non-use, and untreated advanced HIV causes dysbiosis; PubMed also lists a scoping review of raltegravir, dolutegravir and bictegravir (PMID 40650144) and an efavirenz versus dolutegravir comparison (PMID 40521525), which were not opened [24].

Regulatory status

No gut microbiome statement in the label text read [1].

Population evidence

Randomized trial, Catala-Moll 2026 [22]: 88 antiretroviral-naive adults with advanced HIV-1 (median CD4 34 cells/mm3) randomized 1:1 to abacavir/lamivudine + dolutegravir or + darunavir/ritonavir, 2 years follow-up; dolutegravir increased gut microbial richness and diversity and enriched taxa and metabolic pathways, linked to reduced inflammation and immune activation; by 2 years the dolutegravir group resembled people without HIV. p values, diversity metrics and per-arm n were not in the record read (abstract-level, PubMed). Cross-sectional, De Greef 2025 [23]: 79 on dolutegravir, 32 on bictegravir, 10 on non-integrase regimens; weight gain was not associated with overall diversity but with specific taxa (FDR q below 0.01); a model predicted 15.9% of weight change variability.

Mechanism

Not defined; the trial authors attribute the change to treatment of late HIV with a dolutegravir regimen, not to a direct drug-microbe action. Mechanism class G (microbiome disruption affecting endogenous synthesis) was screened: no synthesis outcome was measured.

Cohort test

Dolutegravir was in the cohort in [22][23].

Why yellow

Tier A data exist but show a favorable or non-diversity change, so the entry is a reverse-direction or mixed finding, not a risk of deficiency.

Counter-evidence held on record

Framing caution for the consumer surface Not evidence of harm to gut bacteria or of nutrient loss. Probiotic or dietary advice is not supported by these data.

Oxygen and ATP Output

Oxygen delivery and ATP production are assessed separately. Nothing here is counted twice.

Oxygen delivery/utilization (hemoglobin rose after start; sideroblastic anemia a rare labeled outcome)

Yellow — Low

Evidence: low

Direction: reverse or neutral for hemoglobin; the rare sideroblastic anemia is a labeled clinical outcome and is not filed as an iron, B6 or copper deficiency (Hard Rule 2). Erythrocyte membrane effects are in vitro only.

Full detail and limits

Limits on what this shows

Counter-evidence on record: The study has only a pre-treatment baseline as comparator, so a hemoglobin change cannot be separated from the effect of starting effective ART and cannot be credited to the drug. The in vitro concentrations were not compared with free plasma concentrations (protein binding at least 98.9% [1]).

Regulatory status

Sec 6.2 postmarketing, Blood and lymphatic: sideroblastic anemia [1][2]. No hemoglobin or oxygen-delivery statement in the other label text read.

Population evidence

Gudina 2024, Addis Ababa [19]: 422 adults on dolutegravir/lamivudine/tenofovir disoproxil for at least 3 months, paired before-after comparison; hemoglobin and red cell count increased significantly (P below 0.05; magnitudes not in the record read); after treatment 12.1% had anemia, associated with female sex (adjusted OR 7.8, 95% CI 1.9 to 32.2) and WHO stage III or IV (adjusted OR 16, 95% CI 10.63 to 66.46). No non-dolutegravir comparator. Case reports [20][21]: dolutegravir-induced sideroblastic anemia, AIDS 2024 (no abstract in the record) and Clinical Case Reports 2023 (35-year-old man; iron indices, vitamin B6, copper, marrow findings and course were not retrieved). In vitro eryptosis, Bhuyan 2016 [17]: human erythrocytes, 48 hours; phosphatidylserine exposure increased from 4.8 micromol/L, hemolysis at 19.1 micromol/L, with calcium entry, ceramide and oxidative stress implicated.

Mechanism

Erythrocyte death signaling in vitro [17]; no mechanism for sideroblastic anemia was in the sources read.

Cohort test

Dolutegravir was in the cohort in [19] (as dolutegravir/lamivudine/TDF), [20], [21] (case level) and [17] (in vitro).

Why yellow

Tier B case-level and in vitro plausibility plus a labeled outcome; no directly measured oxygen-delivery deficit. Hemoglobin is not an iron measurement.

Counter-evidence held on record

Framing caution for the consumer surface Not evidence of impaired oxygen delivery or of a deficiency. Unexplained anemia on any ART warrants clinician review; this page makes no supplement recommendation.

ATP production (in vitro redox activity reduced; no in vivo ATP measure)

Yellow — Low

Evidence: low

Direction: unclear. Dolutegravir lowered mitochondrial redox activity in galactose-grown HeLa cells; the abstract summary attributes impaired ATP generation to efavirenz, not dolutegravir. Human adipose respiration was not lower.

Full detail and limits

Limits on what this shows

Counter-evidence on record: No ATP reduction was reported for dolutegravir in the summary read; no in vivo energy output measure was found. Crossref bibliographic search for dolutegravir with ATP and oxidative phosphorylation returned no dolutegravir records.

Regulatory status

No ATP or energy statement in the label text read [1].

Population evidence

George 2021 [15]: HeLa cells forced onto oxidative phosphorylation (glucose replaced by galactose) and BV2 microglia exposed for 24 hours to dolutegravir, emtricitabine or efavirenz at clinically approximating doses; ATP, resazurin redox activity, membrane potential and respiration measured; drug exposure decreased redox activity in HeLa, efavirenz impaired ATP and redox, and BV2 responses differed (quantities not in the record read). Madlala 2025 [14]: complex I and II-linked respiration higher with HIV on the dolutegravir regimen, a respiration not an ATP measurement.

Mechanism

Mitochondrial redox activity reduction in vitro; cell-type dependent [15].

Cohort test

Dolutegravir was tested directly in [15]; in the cohort of [14] as part of a three-drug regimen.

Why yellow

Tier B only, partly tooling-limited: PubMed searches for dolutegravir with ATP and respiration returned invalid-form pages.

Counter-evidence held on record

Framing caution for the consumer surface Not evidence of low cellular energy in people, and not a reason to take energy supplements.

Claims checked and not supported

These circulate online for this medication. They are listed here only so they can be answered, never as findings, and they are not graded.

A claim with no supporting evidence is not necessarily disproven. Where evidence actually argues against a claim, that is stated below.

Folate deficiency caused by dolutegravir (lower circulating folate)
Where it comes from: Extension of the folate receptor antagonism literature and the neural tube defect signal to the whole treated population. The consumer-page version was not traced (WebSearch budget exhausted).
Why it fails: Three trial datasets with dolutegravir in the cohort found folate higher or similar to comparators: ADVANCE women +4.0 and -1.8 nmol/L versus -5.9 on efavirenz [5]; ODYSSEY plasma folate +2.7 ng/mL at week 96 or later, 95% CI 1.7 to 3.7 [6]; VESTED red blood cell folate ratios with CIs crossing 1 [7]. The receptor mechanism is graded yellow under Folate.
Neural tube defects as proof of a dolutegravir-induced folate deficiency
Where it comes from: The first interim Botswana analysis, described in label sec 8.1 [1]. Consumer origin not traced.
Why it fails: Later label data: prevalence at conception 0.11% on dolutegravir versus 0.11% on other regimens (Botswana) and 0.08% versus 0.22% (Eswatini) [1]. A birth defect is an outcome, not a nutrient measurement (Hard Rule 2), and no folate deficit was found in treated women [5][7].
Vitamin D deficiency and bone loss caused by dolutegravir
Where it comes from: Extrapolation from tenofovir disoproxil and efavirenz regimens. Consumer origin not traced.
Why it fails: 25-hydroxyvitamin D change on dolutegravir plus abacavir/lamivudine (-7%, -5%, -2%) did not differ significantly from the efavirenz/emtricitabine/tenofovir arm [10]; lumbar spine density rose 1.6% (0.3 to 2.8%) in a real-world cohort [11]. Bone density is an outcome, not vitamin D status.
Kidney injury or nutrient wasting from the creatinine rise
Where it comes from: Reading the label's creatinine increase as renal damage. Consumer origin not traced.
Why it fails: The label attributes the mean 0.15 mg/dL rise to inhibition of tubular secretion of creatinine (OCT2, and potentially MATE1) [1]. No phosphate, potassium or other tubular nutrient wasting finding appears in the label text read.
Dolutegravir depletes calcium, iron or magnesium
Where it comes from: Reading the cation interaction in the wrong direction. Consumer origin not traced.
Why it fails: The label interaction is the mineral lowering dolutegravir absorption when taken together fasting (AUC 0.61 with calcium carbonate, 0.46 with ferrous fumarate) and not the reverse [2][3]. No study measured mineral status. Hard Rule 4.

How the body handles this medication

Metabolism and enzymes: Dolutegravir is "primarily metabolized via UGT1A1 with some contribution from CYP3A." It is an in vitro substrate of UGT1A3, UGT1A9, BCRP and P-glycoprotein. It did not inhibit the CYP enzymes tested (IC50 above 50 micromol/L) and did not induce CYP1A2, CYP2B6 or CYP3A4 in vitro.[1] Tivicay label sec 7.1, 7.2, 12.3, via summarizing fetch tool
Elimination: After a 14C dose, 53% was excreted unchanged in feces and 31% in urine, mostly as an ether glucuronide (18.9%); renal elimination of unchanged drug was under 1% of the dose. Terminal half-life is about 14 hours; apparent clearance 1.0 L/h; plasma protein binding at least 98.9%.[1] sec 12.3
Absorption and food: Peak concentrations occur 1 to 3 hours after a dose. Low-, moderate- and high-fat meals raised AUC by 33%, 41% and 66% (Cmax by 46%, 52% and 67%) and delayed Tmax to 3, 4 and 5 hours versus 2 hours fasted. The label allows tablets with or without food.[1] sec 2.2, 12.3
Renal tubular handling: Dolutegravir inhibits OCT2 (IC50 1.93 micromol/L) and MATE1 (6.34 micromol/L). The label states it "increase[s] serum creatinine due to inhibition of tubular secretion of creatinine" (mean change 0.15 mg/dL at 96 weeks in treatment-naive adults). Metformin exposure rises: AUC ratio 1.79 at 50 mg once daily and 2.45 at 50 mg twice daily.[1][2] sec 6.1, 7.1, Table 11
Mineral and antacid interactions: Cation-containing antacids, laxatives, sucralfate and buffered medicines: give dolutegravir 2 hours before or 6 hours after. Oral calcium or iron supplements and multivitamins may be taken together with food; fasting, take dolutegravir 2 hours before or 6 hours after. Single-dose AUC ratios: calcium carbonate 1,200 mg fasted 0.61, fed 1.09; ferrous fumarate 324 mg fasted 0.46, fed 0.98, 2 hours after dolutegravir 0.95; Maalox simultaneous 0.26, 2 hours after dolutegravir 0.74; One-A-Day multivitamin simultaneous 0.67.[1] Table 8; [2] Table 12; [3] Table 10
Pregnancy and label postmarketing events: Sec 8.1 reports neural tube defect prevalence in Botswana and Eswatini surveillance (see the Folate entry) and notes those studies lacked data on folic acid use. Postmarketing events listed include weight increased, sideroblastic anemia, acute liver failure, arthralgia, myalgia and anxiety. Sections 12.4 and 13 were not in the text read.[1][2] sec 6.2, 8.1

What the research says is worth watching

General information from the medication label and the studies above. It is not personal medical advice, and any change belongs with your prescriber.

Timing / minerals
Separate dolutegravir from cation products
Cation-containing antacids and laxatives, sucralfate and buffered medicines: dolutegravir 2 hours before or 6 hours after. Oral calcium or iron supplements and multivitamins: together with food, or 2 hours before or 6 hours after when fasting [1]. This is a pharmacist or prescriber conversation, not a reason to stop a mineral.
Pregnancy / folate
Preconception and first trimester
The label gives neural tube defect prevalence data and notes missing folic acid use information in surveillance [1]. Circulating folate was not lower with dolutegravir in three datasets [5][6][7]. Whether and how to supplement folic acid is a prescriber decision; no dose is given here.
Labs / metabolic
Weight, glucose and lipids
Weight gain, lipid change and hyperglycemia are labeled outcomes [1][12]. Monitoring them is routine ART care and says nothing about nutrient status.
Labs / kidney
Interpreting creatinine
Expect a small early rise (label mean 0.15 mg/dL at 96 weeks) from reduced tubular secretion of creatinine [1]. Metformin exposure rises with dolutegravir (AUC ratio 1.79 at 50 mg daily), so the metformin label should be consulted [1][2].
Labs / hematology
Anemia work-up
Sideroblastic anemia is a rare postmarketing event [1][2]. Hemoglobin rose on average after starting dolutegravir in one Ethiopian cohort, with 12.1% anemia at follow-up [19]. Ferritin and iron move with inflammation [18], so interpret them with C-reactive protein.
Symptoms
Sleep and mood
Label sec 6.1: insomnia 3% on dolutegravir + abacavir/lamivudine versus 3% on efavirenz/emtricitabine/tenofovir in SINGLE; suicidal ideation is listed mainly in people with pre-existing depression or psychiatric illness [1]. These are clinical outcomes and no nutrient link was retrieved.

Overlap map, to prevent double counting

Entries that rest on the same underlying source or mechanism. Do not count these as independent confirmation.

Mitochondrial burden
Shares evidence with: Oxidative stress; ATP production
Note: Ajaykumar 2023 [13] (mitochondrial ROS and mass) and Madlala 2025 [14] (adipose respiration) support the first two; George 2021 [15] supports ATP production and mitochondrial redox activity. One body of in vitro mitochondrial work, not three lines of evidence.
Oxidative stress
Shares evidence with: Oxygen delivery/utilization
Note: The Bhuyan 2016 erythrocyte study [17] supplies both the ROS finding and the eryptosis finding.
Oxygen delivery/utilization
Shares evidence with: Iron
Note: The label sideroblastic anemia event [1][2] and case reports [20][21] appear in both entries; they are one signal.
Iron
Shares evidence with: Polyvalent cations
Note: Ferrous fumarate row of the label interaction table [3] is the timing interaction; the Iron entry is about measured iron status [18]. Different questions, one label table.
Folate
Shares evidence with: Polyvalent cations
Note: The zebrafish study [9] (magnesium rescue, calcium no effect) and the cell work [8] (calcium alters receptor interaction) are cited in both entries as mechanistic context only.
Weight gain and metabolic change
Shares evidence with: Gut microbiome risk
Note: De Greef 2025 [23] links taxa to weight change; the weight outcome in the Weight entry is from ADVANCE [12] and the label [1].
Vitamin D
Shares evidence with: (none)
Note: SINGLE [10] and SCOLTA [11] are used only here and in the Fails verification table.

All references used above

Dolutegravir

Findings for this medication

What the research found

Polyvalent cations (calcium, iron, magnesium, aluminum, zinc): nutrient-to-drug timing interaction, not a depletion

Folate (circulating folate not lower; receptor antagonism preclinical; neural tube defect is an outcome)

Vitamin D (25-hydroxyvitamin D fell slightly in both arms; bone density is an outcome)

Weight gain and metabolic change (clinical outcome, not a nutrient deficiency)

The five body-system areas

⚡Mitochondrial Burden

Mitochondrial burden (reversible in vitro stress; human adipose respiration not lower)

💥Oxidative Stress

Oxidative stress (in vitro ROS rise; no clinical antioxidant marker shown to move)

⚖️Copper and Iron Balance

Iron (iron rose and ferritin fell after start; no deficit shown)

Copper

🌿Gut Microbiome Risk

Gut microbiome risk (richness rose versus darunavir; taxa linked to weight gain; reverse or mixed direction)

💨Oxygen and ATP Output

Oxygen delivery/utilization (hemoglobin rose after start; sideroblastic anemia a rare labeled outcome)

ATP production (in vitro redox activity reduced; no in vivo ATP measure)

Claims checked and not supported

Folate deficiency caused by dolutegravir (lower circulating folate)

Neural tube defects as proof of a dolutegravir-induced folate deficiency

Vitamin D deficiency and bone loss caused by dolutegravir

Kidney injury or nutrient wasting from the creatinine rise

Dolutegravir depletes calcium, iron or magnesium

How the body handles this medication

What the research says is worth watching

Overlap map, to prevent double counting

Mitochondrial Burden

Oxidative Stress

Copper and Iron Balance

Gut Microbiome Risk

Oxygen and ATP Output