New HIV diagnosis and baseline assessment

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

A new HIV result creates three immediate questions. First, is infection confirmed or is the result still a reactive screen? Second, does the patient have acute HIV or advanced immune disease that changes today’s clinical priorities? Third, what information is needed to start a fully active and safe regimen? Keeping these questions separate prevents both premature disclosure and dangerous delay.

Fourth-generation laboratory testing detects p24 antigen as well as antibody, but early viraemia can still appear before either marker is conclusive. HIV RNA is therefore a problem-solving test when exposure timing and a compatible illness conflict with serology. Confirmation also identifies situations in which HIV-2 or specialist assays must be considered.

CD4 count and viral load answer different bedside questions. CD4 measures the immune reserve that helps predict opportunistic disease and prophylaxis need. Viral load records untreated replication and becomes the main marker of ART effect. Resistance genotype, HBV status, kidney and liver function then define which complete treatment options are safe.

The first assessment also maps the person’s practical route into long-term care. Medicines, pregnancy intentions, mental health, coercion, housing, confidentiality and pharmacy access can determine whether an excellent prescription is usable. Clear same-day linkage and a named contact reduce loss between diagnosis and treatment.

Rapid ART is the usual direction, but acute organ disease takes precedence over a generic timetable. Pulmonary, CNS and retinal syndromes require their own investigations and treatment, and the diagnosed infection’s guideline governs ART sequencing. This is a clinical decision, not a reason to postpone all treatment planning.

Key points

Screen with a laboratory fourth-generation HIV-1/2 antigen–antibody assay, and submit every reactive result to the national confirmation pathway before calling it a definitive diagnosis.
Very early infection may precede antigen, antibody or rapid-test reactivity, so request HIV RNA when the exposure and illness suggest acute HIV; hypoxia, neurological change or visual loss also triggers immediate syndrome-directed specialist care.
Discuss the result privately and without blame, arrange same-day HIV-service linkage, and before or at ART initiation obtain CD4, viral load, genotype, blood count, renal and liver tests, hepatitis B and C, exposure-site STI tests and pregnancy assessment when relevant.
Use CD4 count to estimate current opportunistic-infection risk and viral load to establish replication, follow treatment response and later confirm transmission suppression.
Complete baseline resistance testing, hepatitis status, medication and interaction history, vaccination review and psychosocial assessment without allowing the checklist to delay urgent care.
Document HLA-B*57:01 negativity before any abacavir prescription; a positive result rules out abacavir and suspected hypersensitivity must never be rechallenged.
Offer ART promptly to nearly everyone, while coordinating infection therapy and the start date through the matched guideline when an opportunistic syndrome is being diagnosed or treated.
Explain that sustained viral suppression on treatment prevents sexual transmission, and verify suppression before using U=U in individual counselling.

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

Sexual acquisition

Transmission follows contact between infectious blood or genital or rectal secretions and susceptible mucosa; probability varies with anatomy, tissue disruption and source viral load.

Injecting or occupational acquisition

Shared injecting equipment and contaminated percutaneous injuries can deliver infected blood beneath the skin barrier, while screened blood supply makes transfusion acquisition uncommon in the UK.

Perinatal acquisition

Without effective care, viraemia can expose an infant before birth, during delivery or through breastfeeding; maternal treatment and the matched pregnancy pathway sharply reduce this risk.

Transmission during undiagnosed early infection

Viral load rises rapidly before full antibody development, so a person may be highly infectious while conventional symptoms are nonspecific and screening remains early.

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

1
Entry into susceptible immune cells
Envelope interaction with CD4 and a chemokine coreceptor permits fusion with T cells and other target cells, starting intracellular replication.
2
Creation of persistent provirus
Reverse-transcribed viral DNA is inserted into cellular DNA, allowing infected long-lived cells to retain the genome even when ART stops active replication.
3
Loss of immune coordination
Repeated infection, cell death and immune activation erode CD4-mediated control, so the spectrum of infection and malignancy broadens as immune reserve falls.
4
Inflammation beyond opportunistic infection
Ongoing viraemia drives systemic immune activation that contributes to vascular, kidney, bone and neurological morbidity, strengthening the rationale for prompt suppression.

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

Acute seroconversion presentationRed flag

Fever, diffuse rash, sore throat, lymphadenopathy, diarrhoea, myalgia, headache or aseptic meningitic symptoms after recent risk should prompt RNA testing when serology is early.

Diagnosis through routine screening

Sexual-health, antenatal, blood-donor or indicator-condition testing often identifies infection before the person has symptoms of immune loss.

Clinical indicator condition

Tuberculosis, recurrent shingles, oral candidiasis, unexplained cytopenia, lymphoma, persistent nodes or severe recurrent bacterial disease should trigger HIV testing.

Advanced immune presentationRed flag

Dyspnoea, wasting, chronic diarrhoea, oesophageal pain, neurological features or atypical skin disease suggests major CD4 depletion and demands same-day assessment.

Result pattern needing HIV-2 expertise

Relevant West African epidemiology, unresolved differentiation or unexpectedly low HIV-1 RNA despite immune deficiency should lead to specialist HIV-2 testing.

Immediate psychosocial riskRed flag

Self-harm thoughts, overwhelming distress, partner violence, coercion, housing insecurity or confidentiality danger need active support during diagnostic care.

Red flags requiring action

Breathlessness with dry cough and hypoxia in advanced HIV raises concern for Pneumocystis pneumonia and requires urgent oxygenation assessment, blood gas and chest imaging.
Headache, confusion, meningism, a focal deficit or reduced consciousness needs urgent specialist CNS investigation; safe sampling and ART sequencing depend on the syndrome found.
New floaters, reduced acuity or a field defect during severe immune suppression requires same-day HIV and ophthalmology review with dilated retinal examination.
A febrile rash illness with pharyngitis or lymphadenopathy after recent exposure may be primary HIV even when an early antigen–antibody result is negative.
Severe weight loss, prolonged diarrhoea, oesophageal symptoms, oral candidiasis or recurrent infection makes advanced immune deficiency clinically likely before the CD4 result returns.
A person receiving a reactive antenatal or donor screen needs prompt confirmation, privacy, support and specialist linkage before the preliminary result is framed as final.

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
Fourth-generation laboratory HIV-1/2 assayFirst step
Why
Detect p24 antigen and antibody as the standard screening step for many established and early infections.
Interpretation and limitations
Reactive is not synonymous with confirmed; an early negative may require repeat or RNA testing according to exposure, symptoms and antiretroviral use.
02
Confirmatory differentiation with nucleic-acid testingConfirmatory
Why
Establish infection type and resolve suspected acute HIV or incomplete serological evolution.
Interpretation and limitations
Use HIV RNA for a convincing early syndrome, while treated infection and HIV-2 can need additional specialist assays and interpretation.
03
CD4 count and percentage
Why
Estimate immune reserve and direct opportunistic-infection assessment and prophylaxis.
Interpretation and limitations
A CD4 count below 200 cells/µL increases PCP concern, but symptoms and acute illness remain part of interpretation rather than being replaced by the number.
04
Baseline HIV viral load
Why
Measure pretreatment replication and provide the reference against which ART response is judged.
Interpretation and limitations
A high value supports acute or uncontrolled infection; later sustained suppression is required before individual U=U advice.
05
Resistance genotype
Why
Reveal transmitted mutations that may reduce activity of a proposed regimen.
Interpretation and limitations
Draw before treatment where possible, begin rapid complete ART when appropriate, and revise the combination if genotype results show reduced activity.
06
Blood count, renal, liver, urine and metabolic profile
Why
Find HIV complications, organ disease and safety constraints before or at treatment initiation.
Interpretation and limitations
Cytopenia or organ dysfunction may reflect HIV, opportunistic illness, coinfection or comorbidity and must be assessed in the clinical context.
07
Hepatitis, STI and infection-risk screen
Why
Identify HBV/HCV, syphilis, site-specific bacterial STI and exposure-driven tuberculosis or toxoplasma issues.
Interpretation and limitations
HBV determines ART-backbone continuity; other tests are selected from history, examination, CD4 count and local epidemiology rather than ordered as an undirected panel.
08
HLA-B*57:01
Why
Prevent abacavir hypersensitivity if an abacavir-containing regimen is under consideration.
Interpretation and limitations
Abacavir is excluded by a positive result, and a patient with suspected previous hypersensitivity must not be exposed again.

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

EBV or CMV mononucleosis

Fever, nodes, sore throat and fatigue can closely resemble seroconversion; exposure timing plus fourth-generation testing and HIV RNA decide whether HIV is present.

Secondary syphilis

Generalised rash and lymphadenopathy may be indistinguishable clinically and coinfection is possible, so treponemal testing belongs in the same evaluation.

Acute viral hepatitis

Malaise, nausea, rash or abnormal liver enzymes after shared sexual or blood exposure requires hepatitis markers alongside HIV testing.

Malignancy or chronic inflammatory disease

Lymphoma, autoimmune disease and drug reactions can explain rash, nodes, weight loss or cytopenias, but they do not remove the need for HIV-specific confirmation.

False-reactive screening result

Screening prioritises sensitivity, so the differentiation and confirmatory pathway must establish whether reactivity represents HIV-1, HIV-2 or no infection.

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

01Reactive resultVerify and communicate diagnosisFirst stepA screening laboratory or point-of-care result has returned reactive.

1Clarify that the result is preliminary, protect privacy and assess immediate emotional safety before giving more technical detail.
2ConfirmatorySend the required confirmatory samples and check whether recent exposure, PrEP or PEP makes HIV RNA particularly important.
3Arrange direct same-day contact with an HIV service and give the patient a named route for results and urgent questions.
4Avoid starting an incomplete antiretroviral regimen while diagnostic status is unresolved.

02First visitMap immune, viral and organ statusHIV has been confirmed and no organ-threatening syndrome is apparent.

1Record symptoms, exposure history, examination, medicines, pregnancy intentions, prior prophylaxis and practical barriers to taking treatment.
2Obtain viral load, CD4, genotype, HLA-B*57:01, blood count, kidney, liver, HBV/HCV and relevant STI or infection tests.
3Select prompt complete ART with the HIV team using resistance, HBV, organ function, pregnancy and interaction information.
4Agree how results, adherence, pharmacy supply, vaccinations, partner care and U=U counselling will be followed.

03Acute illnessLet the organ syndrome leadHypoxia, CNS features, visual symptoms or shock accompanies suspected advanced HIV.

1Stabilise first and involve the appropriate respiratory, neurology, infection or ophthalmology service alongside HIV specialists.
2Use targeted imaging and microbiological or pathological sampling so infection, malignancy and inflammatory causes are distinguished.
3Begin time-critical treatment for the identified syndrome and derive ART sequencing from its matched current guidance.
4Continue baseline HIV work without transferring a treatment interval from a different opportunistic disease.

04CD4 below 200Reduce PCP risk safelySevere immune depletion is confirmed or PCP risk is clinically high.

1Actively ask about breathlessness and dry cough, measure oxygenation and investigate possible active pneumonia before treating the number alone.
2Start co-trimoxazole prophylaxis when the current CD4 and clinical criteria are satisfied, after allergy, renal function and G6PD context are reviewed.
3Use specialist alternatives for serious sulfonamide allergy or toxicity and link stopping to guideline-defined immune recovery.
4Integrate vaccinations, nutrition, eye symptoms, malignancy review and mental-health support into advanced-HIV follow-up.

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

Early full suppression preserves immune function, prevents HIV morbidity and leads to prevention of sexual transmission once undetectability is sustained.

Specialist-selected rapid-start ART

Prescribe a complete approved regimen, commonly once daily and integrase inhibitor based, after baseline samples with adjustment for resistance, HBV, pregnancy, kidney function and interactions.

Never assemble partial treatment; reconcile cations, rifamycins, anticonvulsants and other interacting products, and maintain the HBV-active components required by coinfection.

Provides integrase inhibition with a two-agent nucleoside or nucleotide backbone in one tablet.

Bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg

Take one combined tablet by mouth once daily when the HIV specialist confirms that this complete regimen fits the patient.

Check resistance, HBV, kidney and pregnancy context plus rifamycins, anticonvulsants and polyvalent cations; it is not an automatic choice for every new diagnosis.

Lowers the risk of Pneumocystis pneumonia and also provides activity against toxoplasmosis and selected bacterial infections during severe immune deficiency.

Co-trimoxazole for PCP prophylaxis

Take 960 mg by mouth once daily when prophylaxis is indicated; 480 mg once daily is another guideline-listed dose, with a specialist alternative if allergy or toxicity prevents use.

Review sulfonamide reactions, full blood count, kidney function, potassium, interacting renin–angiotensin drugs and pregnancy; discontinue only after the relevant immune-recovery criteria are met.

Offers a nucleoside option for selected people when virological, HBV and cardiovascular considerations permit.

Abacavir within complete ART

Use only as part of a specialist-designed combination after HLA-B*57:01 negativity has been documented.

Do not prescribe after a positive HLA result and never rechallenge suspected hypersensitivity; it does not supply the HBV activity required in chronic coinfection.

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

Opportunistic infection

Profound CD4 depletion permits pulmonary, neurological, retinal and disseminated pathogens; the organ presentation determines urgent investigation and treatment.

HIV-related malignancy

Immune dysregulation and oncogenic coinfections increase risks including lymphoma, Kaposi sarcoma and anogenital cancers, especially after prolonged uncontrolled infection.

Neurological morbidity

Direct viral effects, vascular disease, malignancy and opportunistic infection can produce cognitive change, neuropathy, focal deficits or altered consciousness.

Chronic non-infectious disease

Persistent replication and inflammation add to conventional cardiovascular, renal, hepatic, metabolic and bone risks over the life course.

Transmission before suppression

Untreated viraemia sustains sexual and perinatal transmission potential; complete ART that achieves durable undetectability removes sexual transmission risk.

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

Close the loop on confirmatory testing and verify that the person has attended or spoken with the receiving HIV team.
Measure viral load after ART begins and continue at treatment-guideline intervals until suppression is documented.
Repeat CD4 according to baseline immune impairment and use recovery to revisit prophylaxis and opportunistic-infection risk.
Track renal, hepatic, haematological and metabolic safety according to the chosen regimen and identified comorbidities.
Ask directly about doses, pharmacy access, interactions, mood, stigma, confidentiality, housing and relationship safety at early reviews.
Complete indicated vaccination, sexual-health, cervical or anal, liver, cardiovascular, renal, bone and malignancy prevention.
Use confirmed sustained viral suppression when explaining U=U, alongside patient-led decisions about contraception, conception and STI prevention.

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

Confirmation and care can coexist

The clinician can offer support and urgent linkage after a reactive screen while remaining precise that laboratory confirmation is still required.

RNA answers an early question

When a convincing seroconversion illness appears before serological closure, direct detection of viraemia can resolve the mismatch.

CD4 and viral load are complementary

One estimates vulnerability to opportunistic disease; the other measures replication and becomes the principal readout of treatment effect.

Baseline tests shape a regimen

Resistance, HBV, kidney, liver, pregnancy and interaction findings prevent rapid ART from becoming poorly matched ART.

U equals U needs a measured state

Explain the prevention benefit early, then anchor individual reassurance to documented sustained viral suppression on treatment.

The diagnosed syndrome sets timing

Pulmonary, CNS and retinal opportunistic disease cannot share one borrowed ART interval; the matched guideline and specialist team direct sequencing.

11Common pitfallsFrequent interpretation and management errors.

01
Do not present a solitary reactive screening result as confirmed HIV.
02
Do not let early negative serology overrule a convincing acute syndrome without RNA assessment.
03
Do not use a normal-looking patient or a pending CD4 count to dismiss organ-specific warning symptoms.
04
Do not delay linkage while waiting for every baseline result, or choose a partial regimen to appear faster.
05
Do not prescribe abacavir without documented HLA-B*57:01 negativity or remove HBV-active ART casually.
06
Do not copy an ART-start interval from one opportunistic infection to another; obtain diagnosis-specific advice.

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