01OverviewDefinition, clinical context and the essential points that orientate the chapter.
ART succeeds when every component contributes to one fully suppressive strategy. Combining classes blocks successive steps in viral replication and makes it harder for a resistant variant to escape. A convenient single tablet may contain the whole regimen, but tablet count alone says nothing about whether it remains active against that patient’s virus.
Initial selection is a constraint-solving exercise. Genotype and treatment history define viral susceptibility; HBV status determines whether HBV-active drugs must remain; kidney, liver, bone and cardiovascular health shape tolerability; pregnancy and tuberculosis may alter agent or dose; and the complete medicines list reveals induction, inhibition, chelation or absorption problems.
Viral load provides the earliest practical verdict on the regimen. A falling value after initiation shows effective suppression. One low detectable value can be a transient blip, whereas a confirmed trajectory prompts a structured check of access, dosing, food, vomiting and interactions before resistance is assumed or therapy is altered.
Switching a suppressed patient still demands resistance reasoning. Archived mutations can remain clinically relevant after they disappear from circulating plasma, and simplification can accidentally expose functional monotherapy. The proposed combination must be fully active, preserve HBV treatment, and receive early post-switch virological review.
Long-term ART care combines virology with the patient’s life. Adverse effects, reproductive goals, mental health, stigma, pharmacy access and cardiovascular prevention all influence durable adherence. The best regimen is one the person can take consistently and safely while retaining full antiviral activity.
Key points
- Treat HIV with a complete combination acting at two or more replication steps; a single antiretroviral drug is not HIV therapy.
- An integrase inhibitor plus two nucleoside or nucleotide agents is a frequent starting framework, but resistance, HBV, pregnancy, kidney function and interactions decide the actual regimen.
- Obtain baseline viral load and genotype, while allowing prompt complete treatment to begin before every result is back when clinically appropriate.
- At initiation, teach the real tablet schedule, food instructions, missed-dose action and any required separation from antacids or mineral products.
- Check prescriptions, non-prescription medicines, supplements and recreational substances against a current HIV interaction resource at every transition.
- Use viral load after starting or changing ART to demonstrate response and repeat until suppression; it is the central efficacy measure.
- In chronic HBV, do not remove two active HBV agents unless an effective alternative and liver and virological monitoring plan is in place.
- For confirmed rebound, investigate adherence and interactions and obtain genotype while the failing regimen still exerts interpretable drug pressure; never add one active drug alone.
02AetiologyUnderlying causes, associations and risk factors, with why each one matters.
Starting treatment before resistance is known
Newly diagnosed infection may carry transmitted mutations, so baseline genotype is drawn while a robust complete regimen is chosen for prompt initiation.
Insufficient drug exposure
Missed tablets, delayed supply, vomiting, food errors or malabsorption can turn a prescribed combination into uneven intracellular coverage and permit replication.
Pharmacological loss of activity
Enzyme induction, gastric pH effects and integrase-inhibitor chelation can lower concentration even when the patient follows the printed dose exactly.
Resistance accumulated over treatment history
Replication under partial pressure selects variants suited to the drugs present; each unsuccessful regimen can add mutations that constrain future combinations.
03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.
- 1Stopping the viral DNA copy
Nucleoside or nucleotide analogues terminate the growing DNA chain, while non-nucleoside agents alter reverse transcriptase so RNA cannot be copied efficiently.
- 2Blocking proviral establishment
Integrase strand-transfer inhibitors prevent viral DNA from being inserted into the host chromosome, sharply reducing successful new cell infection.
- 3Producing non-infectious particles
Protease inhibition prevents cleavage of viral polyproteins, so virions released from the cell do not mature into efficiently infectious particles.
- 4Why combinations prevent escape
Simultaneous pressure at separate stages makes it much less likely that one replicating variant can overcome the whole regimen; low exposure erodes this protection.
04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.
Viral load declines after a fully active regimen begins and reaches assay undetectability while tolerability and adherence remain acceptable.
Headache, nausea, sleep change or gastrointestinal symptoms may improve, but review is needed before they cause missed treatment.
Fever, rash, respiratory or gastrointestinal features after abacavir, or mucosal and organ involvement with any agent, requires urgent expert action.
Repeat detectable viraemia after previous suppression directs attention to supply, dosing, absorption, interaction and resistance rather than an automatic empiric add-on.
Clinical deterioration despite a falling viral load can reveal immune restoration around an occult or recently treated infection and needs syndrome-specific review.
Kidney, bone, liver, lipid, weight or neuropsychiatric changes may emerge over time and justify a planned fully active switch.
05InvestigationsWhat to request, why it matters and how to interpret it.
Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.
- 01
Serial HIV viral loadFirst step - Why
- Determine whether a new regimen suppresses replication and whether control remains durable.
- Interpretation and limitations
- Confirm an unexpected low result before changing stable treatment; persistent or rising viraemia launches adherence, interaction and resistance assessment.
- 02
CD4 count with percentage - Why
- Follow immune restoration and decide whether opportunistic-infection prophylaxis is still required.
- Interpretation and limitations
- Viral load remains the primary efficacy marker; after sustained suppression and immune recovery, CD4 measurement can occur less often.
- 03
Historical and current resistance genotype - Why
- Estimate activity of every component before initiation, switch or rescue treatment.
- Interpretation and limitations
- Genotype during failure is most informative while selective drug pressure remains; archived mutations in old results still count even when absent from plasma.
- 04
Kidney function and urinalysis - Why
- Detect renal disease or tubular injury that affects tenofovir-containing treatment.
- Interpretation and limitations
- Interpret creatinine, eGFR, urine protein and glucose with the regimen: cobicistat may raise serum creatinine by inhibiting secretion without true filtration loss.
- 05
Liver tests and complete HBV markers - Why
- Identify hepatotoxicity and ensure that an ART change will not withdraw necessary hepatitis B treatment.
- Interpretation and limitations
- HBsAg, anti-HBc and anti-HBs are reviewed before backbone changes; ALT rise after withdrawal may signal HBV reactivation.
- 06
Metabolic and cardiovascular assessment - Why
- Track weight, blood pressure, glucose, lipids, smoking and cumulative cardiovascular risk.
- Interpretation and limitations
- Address standard modifiable factors and consider regimen effects without weakening virological activity.
- 07
Regimen-specific interaction check - Why
- Detect enzyme effects, chelation, food dependence and altered acidity that change drug exposure.
- Interpretation and limitations
- Use a current HIV checker with exact formulations and include contraception, antacids, minerals, herbal products and recreational drugs.
06Differential diagnosisRealistic alternatives and the features that help distinguish them.
Transient low-level viraemia
A brief detectable result followed by renewed suppression without a regimen change is a blip, unlike reproducible upward viral load.
Pre-analytical or assay variation
Collection, processing and analytical variation can produce an unexpected value, which is why a clinically stable low result is repeated before treatment is changed.
Adherence barrier without resistance
Cost, supply, disclosure concerns, depression, schedule or food requirements can reduce exposure while the virus remains susceptible and the regimen remains salvageable.
Interaction or malabsorption
Cations, induction, altered acidity, vomiting, diarrhoea or bariatric surgery can explain viraemia despite apparently complete tablet-taking.
Immune reconstitution rather than failure
A patient may worsen from inflammation around an occult infection while viral load is falling, so clinical deterioration and virological failure are not interchangeable.
07ManagementImmediate care, first-line treatment, alternatives and escalation.
01StartConstruct a regimen the virus cannot escapeFirst stepA person with confirmed HIV is ready to begin ART.+
- 1Gather genotype, viral load, CD4, HBV status, HLA-B*57:01, organ function, pregnancy context, prior ART and tuberculosis treatment.
- 2Select a complete guideline-supported combination whose components remain active, using a high resistance barrier when uncertainty is material.
- 3Reconcile every medicine and supplement, then provide exact food, cation and missed-dose instructions for the chosen products.
- 4Agree supply, adherence support and early safety and viral-load follow-up before the patient leaves.
02ResponseUse viral load to test the planART has recently started or the regimen has changed.+
- 1Review symptoms, adherence and access early enough to solve problems before tablets are stopped.
- 2Measure viral load at the treatment-guideline interval and repeat until undetectability is established.
- 3Use targeted renal, liver, blood-count or metabolic tests for the specific agents and clinical risks.
- 4Confirm sustained suppression before individual U=U counselling and continue broader sexual-health and prevention care.
03Detectable resultAssess detectable viral loadViral load appears after prior suppression or does not fall as expected.+
- 1Repeat promptly when assay variation or a transient low-level value is plausible, and compare the full trajectory.
- 2Ask without blame about supply, timing, food, vomiting, antacids, cations, acid suppressants, rifamycins, anticonvulsants and supplements.
- 3Send resistance testing while the patient is still taking the regimen and the viral level supports reliable genotyping.
- 4If failure is confirmed, design a new complete suppressive regimen with resistance specialists instead of adding a solitary active drug.
04Planned switchPreserve hepatitis B-active therapyToxicity, interaction, pregnancy, comorbidity or simplification makes a switch desirable during suppression.+
- 1Review all prior genotypes and treatment exposures, not just the current plasma result, and confirm current suppression.
- 2AlternativeEnsure the proposed regimen remains fully active and retain two HBV-active drugs in chronic HBV or provide expert alternative therapy.
- 3Apply every eligibility condition before choosing a two-drug option, including resistance, HBV, viral-load and pregnancy context.
- 4Repeat viral load and relevant safety tests soon after the switch so loss of control is identified early.
Key medicines and prescribing safety4 treatments · regimens, roles and cautions+
Bictegravir/emtricitabine/tenofovir alafenamide
Take one tablet containing 50 mg/200 mg/25 mg by mouth once daily when selected as the complete regimen.Review genotype, HBV, kidney and pregnancy context, rifamycins, anticonvulsants and polyvalent-cation instructions before prescribing or stopping.
Dolutegravir with tenofovir disoproxil/emtricitabine
Take dolutegravir 50 mg by mouth once daily plus tenofovir disoproxil 245 mg/emtricitabine 200 mg once daily when specialist selected.Rifampicin can require a dolutegravir dose adjustment; address cation timing and renal or bone risk, and do not interrupt HBV-active cover casually.
Dolutegravir/lamivudine
Take one tablet containing dolutegravir 50 mg and lamivudine 300 mg by mouth once daily only after every two-drug eligibility criterion is met.Exclude chronic HBV, relevant or uncertain resistance and an unsuitable high baseline viral-load setting; check pregnancy guidance and cation exposure.
Darunavir boosted with ritonavir
Outside pregnancy, take darunavir 800 mg with ritonavir 100 mg by mouth once daily with food when selected. When initiating during pregnancy, use darunavir 600 mg with ritonavir 100 mg twice daily; once-daily treatment begun before conception may continue after specialist review if suppression is maintained.Pregnancy changes exposure and dosing. Check major CYP interactions, liver disease, lipids and sulfonamide history, and never omit the prescribed booster or active companion drugs.
08ComplicationsImportant consequences, why they occur and why they matter clinically.
Persistent viraemia
Failure to suppress prevents full immune recovery, maintains transmission potential and gives resistance further opportunity to evolve.
Narrowed future treatment options
Accumulated mutations across drug classes can leave too few tolerable fully active agents for an ordinary regimen and require specialist rescue therapy.
Return of opportunistic disease
Ongoing replication and falling CD4 reserve can restore susceptibility to serious infection and HIV-associated malignancy despite tablets remaining on the medication list.
Treatment-related organ morbidity
Renal, hepatic, metabolic, skeletal or neuropsychiatric adverse effects can undermine health and adherence unless trends are recognised and a fully active alternative is planned.
HBV reactivation during an ART change
With chronic coinfection, removing effective HBV-active agents permits rapid HBV replication and potentially severe hepatic inflammation.
09Monitoring and follow-upTreatment response, safety checks and longer-term review.
- Check viral load after initiation or switch and repeat at the recommended intervals until undetectability is clear.
- Use CD4 recovery to review opportunistic-infection prophylaxis while keeping viral load as the main treatment-effect measure.
- Monitor eGFR and urine findings when tenofovir disoproxil or another renal risk is present.
- Follow liver enzymes and HBV virology closely whenever HBV-active components change.
- Track weight, blood pressure, glucose, lipids, smoking and cardiovascular risk, then treat modifiable factors.
- At every prescribing transition, confirm supply, adherence, food instructions and all newly introduced interacting products.
- Record sustained suppression, U=U discussion, reproductive goals, contraception interactions, vaccinations, STI testing and appropriate cancer screening.
10Special situationsVariants, exceptions and circumstances that change the usual approach.
Complete means fully active
A multi-tablet prescription can still be functionally incomplete if resistance or an interaction removes the activity of one component.
Viral load judges efficacy
CD4 recovery describes immune benefit, while serial viraemia most directly shows whether the regimen is stopping replication.
One detectable value needs context
Confirm the trend and examine access, absorption and interactions before labelling a stable patient as virologically failing.
Cations matter at the bedside
Calcium, iron, magnesium and aluminium can chelate integrase inhibitors, making ordinary supplements clinically relevant to viral control.
Old mutations remain relevant
A mutation selected years earlier may be archived below present plasma detection yet re-emerge when a switch relies on the affected drug.
HBV changes every backbone switch
Lamivudine alone is insufficient HBV treatment, and withdrawal of tenofovir-based suppression can precipitate serious rebound hepatitis.
11Common pitfallsFrequent interpretation and management errors.
- 01
Do not equate a single tablet with a regimen that is necessarily active against this patient’s virus.
- 02
Do not use HIV monotherapy or add one active agent to a failing combination.
- 03
Do not make a switch from the current genotype alone when archived resistance records exist.
- 04
Do not diagnose resistance from one low detectable result before repeating viral load and reviewing exposure.
- 05
Do not omit antacids, minerals, herbal products, contraception or recreational drugs from interaction review.
- 06
Do not interrupt treatment at care transitions without reconciling the regimen and preserving HBV therapy.