New HIV diagnosis and baseline assessment

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

HIV infects CD4 T lymphocytes, macrophages and dendritic cells through CD4 and chemokine coreceptors. Untreated replication progressively impairs cellular immunity, enabling opportunistic infection, malignancy and chronic inflammatory organ injury.

Fourth-generation laboratory tests detect p24 antigen and HIV-1/2 antibodies, shortening the diagnostic window. A reactive screen is preliminary until the confirmatory laboratory algorithm distinguishes HIV-1, HIV-2 and false reactivity.

Baseline assessment is broader than CD4 count. It establishes viral burden, resistance, organ safety, coinfection, vaccination need, pregnancy, cardiovascular and bone risk, mental health, medication interaction and practical barriers to care.

Modern ART permits normal life expectancy and prevents sexual transmission when viral suppression is sustained. Rapid linkage and a person-centred explanation reduce anxiety, loss to follow-up and onward transmission.

Key points

Use a laboratory fourth-generation HIV-1/2 antigen–antibody assay as the standard screening test and follow the national confirmatory algorithm after a reactive result.
During very early infection, antigen, antibody and rapid tests may be negative; request HIV RNA when acute HIV is strongly suspected.
Communicate a new diagnosis privately, non-judgmentally and with a clear same-day linkage plan; assess immediate mental-health and safeguarding needs.
Obtain baseline HIV viral load, CD4 count, resistance genotype, full blood count, renal, liver, bone and metabolic profile before or at ART initiation.
Test hepatitis B and C, syphilis and exposure-site STIs; assess tuberculosis, toxoplasma and other infections according to history and CD4 count.
Check HLA-B*57:01 before abacavir and never use abacavir in a positive patient.
Start ART rapidly for nearly everyone, but coordinate timing with treatment of cryptococcal meningitis, TB meningitis and selected unstable opportunistic infections.
Explain that sustained undetectable viral load on treatment prevents sexual transmission: undetectable equals untransmittable.

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

Sexual transmission

HIV crosses genital or rectal mucosa through infected blood, semen, vaginal or rectal fluid during exposure.

Blood exposure

Shared injecting equipment, a contaminated needlestick or unscreened blood can introduce infected cells or free virus directly into the bloodstream.

Vertical transmission

Untreated maternal virus passes during pregnancy, birth or breastfeeding, while effective ART greatly reduces each route.

Acute high-viraemia transmission

Early infection produces very high viral load before antibody tests become fully reactive, increasing transmission probability during this often undiagnosed phase.

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

1
CD4-cell entry
Viral envelope binds CD4 and CCR5 or CXCR4 coreceptors, enabling fusion and RNA entry into susceptible cells.
2
Proviral integration
Reverse-transcribed viral DNA integrates into the host genome, establishing long-lived cellular reservoirs that persist despite otherwise fully suppressive antiretroviral therapy.
3
Progressive immune loss
Ongoing viral replication and inflammation progressively deplete or dysregulate CD4 cells, weakening pathogen-specific immunity and permitting opportunistic disease.
4
Chronic systemic inflammation
Microbial translocation and immune activation contribute to cardiovascular, renal, bone, neurological and malignant complications despite partial control.

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

Acute retroviral syndromeRed flag

Fever, rash, sore throat, lymphadenopathy, myalgia, diarrhoea, headache or aseptic meningitis occurs weeks after some acquisitions.

Asymptomatic diagnosis

Screening during sexual-health care, pregnancy, blood testing or indicator-condition assessment identifies many people before immune symptoms.

Indicator conditions

Recurrent shingles, oral candidiasis, unexplained cytopenia, weight loss, persistent lymphadenopathy, TB, lymphoma or severe bacterial infection prompts testing.

Advanced immune deficiencyRed flag

Wasting, oesophageal candidiasis, chronic diarrhoea, dyspnoea, neurological disease and unusual skin lesions suggest low CD4 count.

HIV-2 possibility

West African epidemiology, indeterminate differentiation or low viral load despite advanced immune deficiency should prompt HIV-2 expertise.

Psychosocial crisisRed flag

Acute distress, self-harm thoughts, coercion, insecure housing, immigration concern or partner violence requires immediate supportive assessment.

Red flags requiring action

Breathlessness, dry cough and hypoxia with advanced HIV suggests Pneumocystis pneumonia and needs urgent blood gas and imaging.
Headache, confusion or meningism can represent cryptococcal, tuberculous or other CNS infection and requires urgent lumbar-puncture planning.
Visual floaters, field loss or reduced acuity in severe immune suppression requires same-day retinal examination for CMV.
Acute fever, rash, pharyngitis and lymphadenopathy after recent exposure may be primary HIV despite an initially negative antibody test.
Severe weight loss, chronic diarrhoea, oral or oesophageal candidiasis and recurrent infections suggest advanced immune deficiency.
A reactive antenatal or blood-donor screen needs urgent confirmatory testing and supportive specialist communication, not delayed or casual disclosure.

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 HIV antigen–antibody assayFirst step
Why
Screen for established and many early HIV-1 or HIV-2 infections using venous laboratory testing.
Interpretation and limitations
A reactive result enters the confirmatory algorithm; a negative result may be too early after exposure and requires window-period or RNA assessment.
02
HIV differentiation and nucleic-acid confirmation
Why
Confirm HIV and distinguish HIV-1, HIV-2 or acute infection when serology is incomplete.
Interpretation and limitations
HIV RNA detects early infection, but some treated or HIV-2 cases need specialist assays; never report one reactive screen as final alone.
03
CD4 count and percentage
Why
Quantify immune impairment and determine urgency, prophylaxis and opportunistic-infection risk.
Interpretation and limitations
CD4 below 200 cells/µL increases PCP risk; acute illness can transiently alter count, so interpret with the clinical picture.
04
HIV viral load
Why
Establish baseline replication and later measure ART response and transmission suppression.
Interpretation and limitations
Very high load supports acute or untreated infection; an unexpectedly undetectable result requires treatment history, HIV-2 and assay review.
05
Genotypic resistance test
Why
Detect transmitted resistance before selecting or modifying the initial regimen.
Interpretation and limitations
Send before ART when possible, but do not delay urgent treatment; integrase testing follows national and exposure-specific recommendations.
06
Baseline safety and HLA-B*57:01
Why
Assess blood count, kidney, liver, glucose, lipids, bone and abacavir hypersensitivity risk.
Interpretation and limitations
HLA-B*57:01 positivity permanently excludes abacavir; renal and hepatitis results materially affect tenofovir and backbone choice.
07
Coinfection and prevention screen
Why
Identify hepatitis, TB, toxoplasma, STI, cervical disease and vaccination needs.
Interpretation and limitations
Use exposure, country and CD4 count to choose tests; hepatitis B status must be known before selecting or stopping HBV-active ART.

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

Infectious mononucleosis

EBV and CMV cause fever, pharyngitis, rash and lymphadenopathy that overlap acute HIV; fourth-generation testing plus HIV RNA resolves early uncertainty.

Secondary syphilis

Secondary syphilis causes generalised rash, lymphadenopathy and systemic symptoms, so parallel treponemal testing is required because mimicry and coinfection are common.

Viral hepatitis

Acute hepatitis produces malaise, nausea, rash and abnormal liver tests after some shared blood or sexual exposures.

Malignancy

Lymphoma and other cancers cause weight loss, nodes and cytopenias and can coexist with advanced HIV.

Medication or autoimmune disease

Drug eruptions, lupus and inflammatory disorders can mimic acute HIV rash or cytopenia, but diagnosis requires HIV-specific antigen, antibody or RNA evidence.

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

01CONFIRMVerify and communicate diagnosisFirst stepAn HIV screen is reactive or acute infection remains likely despite negative screening.

1ConfirmatorySend the national confirmatory differentiation and nucleic-acid tests and urgently request HIV RNA when acute infection is suspected.
2Explain that a screening result needs confirmation, maintain privacy and assess immediate emotional safety and support preferences.
3Take a focused exposure, previous test, PrEP or PEP, ART, pregnancy and symptom history without assigning blame.
4Link directly to an HIV specialist team and ensure the patient knows exactly when, where and how follow-up will occur.

02BASELINEMap immune, viral and organ statusHIV is confirmed or specialist assessment proceeds while confirmation is being resolved.

1Obtain CD4 count, viral load and resistance genotype before or at treatment initiation.
2Check full blood count, renal and liver profile, urine, glucose or HbA1c, lipids and bone risk and perform HLA-B*57:01 if abacavir may be used.
3Test hepatitis A, B and C, syphilis and exposed STI sites and assess TB, toxoplasma and pregnancy.
4Examine for oral, skin, lymph-node, neurological, respiratory and retinal evidence of advanced disease.

03STARTBegin ART rapidly and safelyBaseline specimens are taken and no untreated opportunistic infection requires a different timing plan.

1Select a potent integrase-inhibitor-based regimen with the HIV team, accounting for resistance, HBV, pregnancy, renal function and interactions.
2Start as soon as practical rather than waiting for every routine result, while retaining a route to modify when genotype returns.
3Provide a written dosing and interaction plan, adherence support and access for early adverse effects.
4Measure viral load after starting and continue until suppression is documented and sustained.

04ADVANCEDProtect severe immune deficiencyCD4 is below 200 cells/µL or symptoms suggest an opportunistic infection.

1Investigate each acute syndrome before attributing it to HIV alone and start time-critical infection treatment.
2Begin co-trimoxazole prophylaxis when current CD4 and clinical criteria are met after checking allergy, renal function and G6PD context.
3Coordinate ART timing with the identified infection, delaying only when evidence supports reduction of immune-reconstitution harm.
4Provide vaccination, nutrition, malignancy, eye and mental-health assessment within an advanced-HIV care plan.

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

Suppresses viral replication, restores immune function and prevents morbidity and sexual transmission.

Rapid-start antiretroviral regimen

Use the exact specialist-selected once-daily integrase-inhibitor-based combination after baseline specimens, adjusted for resistance, hepatitis B, pregnancy, kidney function and interactions.

Do not improvise a partial regimen; check polyvalent cations, rifamycins, anticonvulsants, acid suppressants and whether HBV-active agents must be maintained.

Provides a potent single-tablet integrase-based option for suitable HIV-1 infection.

Bictegravir, emtricitabine and tenofovir alafenamide

Give one 50 mg/200 mg/25 mg tablet orally once daily when the HIV specialist selects this complete regimen.

Not suitable for every renal, pregnancy, resistance or interaction context; review rifamycins, anticonvulsants, polyvalent cations and hepatitis B before stopping.

Prevents Pneumocystis pneumonia and adds protection against toxoplasmosis and selected bacterial infection in advanced immune deficiency.

Co-trimoxazole prophylaxis

Give 960 mg orally once daily when PCP prophylaxis is indicated, using a specialist alternative if severe sulfonamide allergy or toxicity prevents it.

Check rash history, blood count, renal function, potassium, interacting renin–angiotensin medicines and pregnancy; stop only after guideline-defined immune recovery.

Provides an alternative nucleoside backbone component for selected patients.

Abacavir only after HLA testing

Use only within a complete specialist antiretroviral regimen after documented HLA-B*57:01 negativity.

Never prescribe when HLA-B*57:01 positive or rechallenge after suspected hypersensitivity; review cardiovascular, hepatitis B and resistance considerations.

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

Opportunistic infection

Falling CD4 count permits Pneumocystis, tuberculosis, cryptococcus, toxoplasma, CMV and other pathogens to cause invasive disease.

HIV-associated malignancy

Immune dysfunction and oncogenic viruses increase lymphoma, Kaposi sarcoma, cervical, anal and other cancer risk, particularly with prolonged uncontrolled viraemia.

Neurological disease

Direct viral injury, opportunistic infection and vascular or malignant complications cause cognitive, peripheral and focal neurological syndromes.

Chronic organ disease

Untreated replication and chronic inflammation accelerate cardiovascular, renal, liver, bone and metabolic morbidity alongside conventional age-related and behavioural risk factors.

Vertical and sexual transmission

Detectable untreated viraemia permits transmission, while sustained suppression on ART prevents sexual transmission and markedly reduces perinatal risk.

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

Confirm attendance with the HIV specialist service and resolve every outstanding confirmatory result.
Review viral load after ART initiation and at intervals until undetectable, then according to stable-care guidance.
Repeat CD4 to document immune recovery, especially when baseline count determines prophylaxis or opportunistic-infection risk.
Monitor renal, hepatic, metabolic and haematological safety according to the chosen regimen and comorbidities.
Review adherence, pharmacy access, interactions, mood, stigma, housing, immigration and partner or family support at early visits.
Complete vaccines and cervical, anal, liver, cardiovascular, renal, bone and cancer prevention appropriate to age and risk.
Explain U=U only after viral suppression is confirmed and sustained, while maintaining shared decisions on STI prevention and conception.

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

A screen is preliminary

False-reactive results occur, so definitive communication follows the confirmatory algorithm while support begins immediately.

Acute infection can escape serology

HIV RNA becomes detectable before a fourth-generation assay and is requested when recent exposure and syndrome are convincing.

CD4 guides infection risk

Viral load measures replication and transmission response, while CD4 count more directly maps opportunistic-infection susceptibility.

HBV changes backbone decisions

Stopping tenofovir plus emtricitabine or lamivudine in hepatitis B can trigger severe hepatic flare.

U equals U is evidence based

Sustained undetectable viral load on effective treatment prevents sexual HIV transmission and should be communicated clearly.

CNS infection changes timing

Immediate ART is usual, but cryptococcal and TB meningitis require specialist sequencing to reduce dangerous intracranial inflammation.

11Common pitfallsFrequent interpretation and management errors.

01
Do not communicate one reactive screening assay as a final diagnosis without confirmation.
02
Do not exclude acute HIV after an early negative antibody or antigen test.
03
Do not delay urgent linkage while waiting for every baseline result.
04
Do not start abacavir before documented HLA-B*57:01 negativity.
05
Do not choose or stop tenofovir-based ART without hepatitis B status.
06
Do not start ART blindly in suspected cryptococcal or TB meningitis without urgent specialist sequencing.