Antiretroviral treatment and monitoring

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Antiretroviral therapy combines agents from different classes to suppress HIV replication below assay detection, permit CD4 recovery, prevent illness and eliminate sexual transmission when suppression is sustained.

Modern regimens are potent and often contained in one daily tablet, but no product suits every patient. Resistance, HIV-2, hepatitis B, pregnancy, renal and bone health, cardiovascular risk, tuberculosis treatment and drug interactions determine selection.

Viral load is the principal efficacy measure. A transient low-level blip may resolve, while confirmed rebound suggests missed doses, impaired absorption, interaction or resistance and demands a structured response.

Long-term care integrates organ safety, metabolic and cardiovascular prevention, vaccination, cancer screening, sexual health, reproductive goals and mental wellbeing. Regimen simplicity is valuable only when it remains fully active and safe.

Key points

ART uses a complete combination that blocks at least two viral replication targets; never prescribe HIV monotherapy.
An integrase inhibitor with two nucleoside or nucleotide agents is a common initial strategy, but resistance, hepatitis B, pregnancy, renal function and interactions determine the exact regimen.
Take a baseline resistance genotype and viral load, but rapid treatment usually begins before every result returns and is modified if necessary.
Explain the exact tablet schedule, food requirement, missed-dose plan and interaction separation before the first dose.
Check all prescribed, over-the-counter, recreational and complementary substances through a current HIV interaction resource.
Measure viral load after starting or changing ART and continue until suppression; viral load is the main marker of treatment success.
Do not switch away from two active hepatitis B agents without a deliberate HBV treatment and liver-monitoring plan.
Investigate confirmed rebound with adherence and resistance testing while the failing regimen still provides interpretable selective pressure.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Treatment-naive infection

Initial therapy addresses actively replicating virus before drug selection has imposed resistance, using baseline genotype and host factors.

Adherence interruption

Missed doses, supply gaps, vomiting or unstable circumstances lower effective exposure and permit replication under partial pressure.

Drug interaction

Enzyme induction, polyvalent-cation chelation or altered gastric acidity can reduce antiretroviral exposure despite correct prescribed dosing and reported adherence.

Transmitted or acquired resistance

Viral mutations present before treatment or selected during incomplete suppression reduce activity of one or more regimen components.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Reverse-transcriptase blockade
Nucleoside and non-nucleoside agents prevent conversion of viral RNA into DNA through chain termination or allosteric reverse-transcriptase inhibition.
2
Integrase inhibition
Integrase strand-transfer inhibitors prevent insertion of viral DNA into host chromosomes and rapidly reduce new infection cycles.
3
Protease inhibition
Protease inhibitors prevent cleavage of viral polyproteins, so released virions remain structurally immature and unable to establish efficient new infection.
4
Resistance selection
Viral replication during subtherapeutic drug exposure favours resistant variants, and sequential incomplete regimens can accumulate mutations across several drug classes.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Successful suppression

Viral load falls rapidly after initiation and becomes undetectable while adherence, tolerability and CD4 recovery remain satisfactory.

Early intolerance

Nausea, headache, insomnia or mild gastrointestinal effects may settle, but severity and adherence impact require active review.

Drug hypersensitivityRed flag

Fever, rash, gastrointestinal or respiratory symptoms after abacavir or systemic mucosal disease with another agent needs urgent cessation planning.

Virological reboundRed flag

A confirmed rising viral load after previous suppression suggests adherence interruption, interaction, absorption problem or resistance.

Immune reconstitutionRed flag

Inflammatory deterioration after starting ART may unmask tuberculosis, cryptococcus or another infection despite virological improvement.

Long-term toxicity

Renal, bone, lipid, weight, liver or neuropsychiatric change may emerge gradually and prompt risk-based switching.

Red flags requiring action

Never rechallenge abacavir after suspected hypersensitivity because recurrence can be rapidly fatal.
Stopping tenofovir plus emtricitabine or lamivudine in hepatitis B can precipitate a severe hepatic flare.
A newly detectable viral load requires adherence, interaction and resistance assessment before empirically adding one drug.
Rifampicin, anticonvulsants, polyvalent cations and acid suppressants can make an otherwise potent regimen fail.
Pregnancy with detectable viral load, vomiting or missed treatment needs same-day HIV maternity review.
Severe rash with mucosal, liver or systemic involvement requires urgent drug-reaction assessment.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

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
HIV viral loadFirst step
Why
Quantify response after initiation or switch and detect loss of suppression.
Interpretation and limitations
Repeat an unexpected low detectable result; confirmed upward trend or above-threshold rebound triggers adherence, interaction and resistance review.
02
CD4 count and percentage
Why
Document immune recovery and determine need for opportunistic-infection prophylaxis.
Interpretation and limitations
Once stable above relevant thresholds with suppression, CD4 testing can be less frequent than viral-load monitoring.
03
Resistance genotype
Why
Identify mutations affecting nucleoside, non-nucleoside, protease or integrase activity before and during failure.
Interpretation and limitations
Obtain while the patient is taking the failing regimen or soon after stopping because resistant variants may become less detectable.
04
Renal and urine assessment
Why
Monitor tenofovir exposure, tubular function and comorbid renal disease.
Interpretation and limitations
Creatinine, eGFR, urine protein and glucose patterns guide TDF avoidance or switch; cobicistat can raise creatinine without reducing filtration.
05
Liver and hepatitis B assessment
Why
Detect hepatotoxicity and ensure continuous HBV-active treatment.
Interpretation and limitations
HBsAg, anti-HBc and anti-HBs status precedes backbone changes; ALT flare after withdrawal can indicate HBV reactivation.
06
Metabolic and cardiovascular profile
Why
Monitor lipids, glucose, weight, blood pressure and cumulative cardiovascular risk.
Interpretation and limitations
Treat standard risk factors and consider regimen contribution without compromising virological activity.
07
Medication-interaction review
Why
Identify induction, inhibition, chelation and absorption effects before prescribing or switching.
Interpretation and limitations
Use a current HIV interaction checker and include antacids, mineral supplements, herbal agents, contraception and recreational drugs.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Transient viral-load blip

A brief low detectable value returns to suppression without regimen change and differs from sustained upward rebound.

Laboratory or sample issue

Processing error, contamination or assay variation can create an unexpected viral-load result; repeat testing should confirm rebound before a stable regimen is changed.

Poor absorption

Vomiting, diarrhoea, bariatric surgery or failure to meet a medicine's food requirement can lower exposure despite adherence and no resistance mutation.

Drug toxicity

Renal, liver, metabolic or neuropsychiatric disease may arise from ART, comorbidity or another medicine and requires attribution.

Immune-reconstitution syndrome

Inflammatory worsening after effective viral suppression can reflect immune-reconstitution syndrome rather than virological failure, particularly around recently treated opportunistic infection.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01SELECTBuild a complete active regimenFirst stepART is starting or a planned switch is being considered.

1Review resistance, viral load, CD4, hepatitis B, HLA-B*57:01, kidney, liver, pregnancy, tuberculosis and previous ART.
2Choose an approved complete regimen with at least two fully active components and a high resistance barrier when uncertainty exists.
3Check every medicine and supplement for interactions and document food and polyvalent-cation instructions.
4Take baseline safety tests, agree adherence supports and prescribe enough supply to prevent avoidable interruption.

02MONITORConfirm suppression and safetyA new or modified antiretroviral regimen has begun.

1Review tolerability and adherence within the early weeks and measure viral load at the guideline interval after initiation.
2Repeat viral load until undetectable, then monitor at stable-care intervals with CD4 according to immune status.
3Check regimen-specific renal, liver, blood-count and metabolic markers and act on trends rather than isolated values.
4Reinforce U=U after sustained suppression and continue STI, vaccination and comorbidity prevention.

03REBOUNDInvestigate detectable viral loadViral load becomes newly detectable or fails to suppress as expected.

1Repeat viral load promptly when a laboratory blip is possible and confirm the trajectory.
2Use a non-judgmental adherence review covering supply, timing, food, vomiting, cations, acid suppression, rifamycins, anticonvulsants and supplements.
3Send resistance testing while the regimen is still being taken when the viral level permits reliable genotyping.
4Construct a new fully suppressive regimen with HIV resistance specialists rather than adding one active drug to a failing combination.

04SWITCHChange treatment without creating gapsToxicity, interaction, simplification, pregnancy or comorbidity justifies a regimen change despite suppression.

1Confirm viral suppression, full treatment and resistance history and the activity of every proposed component.
2AlternativePreserve two HBV-active agents in chronic hepatitis B or establish an alternative HBV treatment plan.
3Check that a two-drug regimen meets viral-load, resistance, hepatitis and pregnancy criteria before selection.
4Measure viral load and safety soon after switching and restore an active regimen urgently if rebound occurs.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Combines an integrase inhibitor with two nucleoside or nucleotide agents in a single daily tablet.

Bictegravir, emtricitabine and tenofovir alafenamide

Give one tablet containing 50 mg/200 mg/25 mg orally once daily when selected as a complete regimen.

Check resistance, renal and pregnancy context, hepatitis B, rifamycins, anticonvulsants and separation from polyvalent cations.

Provides a potent integrase-based three-drug regimen with two hepatitis B-active backbone agents.

Dolutegravir plus tenofovir disoproxil and emtricitabine

Give dolutegravir 50 mg orally once daily plus tenofovir disoproxil 245 mg and emtricitabine 200 mg orally once daily when specialist-selected.

Rifampicin may require dolutegravir dose adjustment; separate cations, assess renal and bone risk and never stop HBV-active agents casually.

Maintains or initiates suppression without tenofovir in selected patients with susceptible virus.

Dolutegravir and lamivudine

Give one tablet containing dolutegravir 50 mg and lamivudine 300 mg orally once daily only when all two-drug eligibility criteria are met.

Do not use with hepatitis B, relevant resistance, uncertain genotype or an unsuitable high baseline viral-load setting; check cations and pregnancy guidance.

Provides a high genetic barrier in selected resistance, adherence or pregnancy scenarios as part of complete ART.

Boosted darunavir regimen

Give darunavir 800 mg with ritonavir 100 mg orally once daily with food when a specialist selects a boosted-protease-inhibitor combination.

Major CYP interactions, lipid effects, liver disease and sulfonamide history require review; never use without the prescribed booster and active backbone.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Virological failure

Persistent viral replication prevents immune recovery, permits transmission and selects additional resistance mutations, progressively narrowing future treatment choices.

Opportunistic disease

Incomplete suppression with declining CD4 count restores susceptibility to opportunistic infections and HIV-associated malignancy despite apparent continuation of therapy.

Multiclass resistance

Sequential partially active regimens accumulate resistance mutations and can leave too few fully active, tolerable agents for a durable combination.

Organ toxicity

Renal, hepatic, metabolic, bone or neuropsychiatric adverse effects can cause morbidity and undermine adherence unless detected through symptom-led and scheduled monitoring.

Hepatitis B flare

Withdrawal of HBV-active tenofovir and companion agents permits abrupt hepatitis B replication and severe liver inflammation.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Measure viral load after initiation or switch and repeat until suppression is documented.
Use CD4 results to start or stop opportunistic-infection prophylaxis and then reduce frequency after durable immune recovery.
Check renal function and urinalysis for tenofovir disoproxil and other kidney-risk regimens.
Monitor liver enzymes and hepatitis B markers during any change in HBV-active drugs.
Track weight, blood pressure, lipids, glucose, smoking and cardiovascular risk and treat modifiable factors.
Review adherence, medicine supply, food requirements and interaction changes at every prescribing transition.
Document U=U, reproductive goals, contraception interactions, vaccines, STI testing and age-appropriate cancer screening.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Undetectable measures success

CD4 recovery is important, but viral load is the immediate and most sensitive indicator that the regimen is suppressing replication.

A blip is not automatic failure

One low detectable result can be transient; confirm the trend before changing a well-tolerated complete regimen.

Cations chelate integrase inhibitors

Calcium, iron, magnesium and aluminium can reduce absorption unless timing and food instructions are followed.

Cobicistat changes creatinine

Tubular creatinine secretion is inhibited, raising serum creatinine without necessarily reducing true glomerular filtration.

Resistance history never disappears

Archived mutations may be absent from a current plasma genotype but remain relevant to every future switch.

HBV needs continuous suppression

Lamivudine alone is inadequate HBV treatment and withdrawal of tenofovir-based cover can cause dangerous flare.

11Common pitfallsFrequent interpretation and management errors.

01
Do not prescribe a single antiretroviral agent as HIV treatment.
02
Do not switch a suppressed patient without reviewing archived resistance and hepatitis B.
03
Do not interpret one low viral-load blip as definite resistance.
04
Do not add one active drug to a failing regimen.
05
Do not ignore antacids, supplements, herbal products or recreational-drug interactions.
06
Do not interrupt ART because another clinician has not reconciled the regimen.