HIV is a retrovirus. There are two types: HIV-1 (responsible for the global pandemic) and HIV-2 (limited primarily to West Africa). ^[1]

Replication steps (directly from slides) ^[1]:

1. HIV enters the host most often through anogenital mucosa
2. HIV enters CD4+ T lymphocytes through binding of viral glycoproteins (gp120/gp41) to the CD4 receptor + a co-receptor (CCR5 or CXCR4)
3. Intracellularly, reverse transcriptase transcribes the RNA genome to DNA
4. Integration of HIV DNA into the host genome (by integrase)
5. HIV matures by proteases releasing individual HIV proteins

Why this matters: Each step is a drug target:

• Entry/fusion → fusion inhibitors, CCR5 antagonists
• Reverse transcription → NRTIs, NNRTIs
• Integration → INSTIs (integrase strand transfer inhibitors)
• Protease cleavage → PIs

Key structural proteins of the HIV virion (from slide diagram) ^[1]:

• Envelope: gp120 (surface), gp41 (transmembrane)
• Matrix: p17
• Capsid (core): p24 — this is the antigen detected in 4th-generation ELISA
• Nucleocapsid: p7, p6
• Enzymes within the core: reverse transcriptase, integrase, protease
• Accessory protein: Vpr

HIV causes immune destruction through CD4 T-cell depletion. The outcomes of immune dysfunction are infections and malignancy. ^[1]

Two mechanisms of CD4+ T-lymphocyte destruction ^[1]:

1. Direct virus-mediated destruction — HIV directly kills the CD4+ T cell it infects
2. Immune destruction — HIV-specific cytotoxic T lymphocytes (CTLs) kill HIV-infected CD4+ T cells

Both pathways contribute to the progressive CD4 depletion that defines HIV disease.

Why CD4 depletion matters: CD4+ T-helper cells orchestrate the adaptive immune response. As CD4 counts fall, the patient becomes progressively vulnerable to opportunistic infections (OIs) in a predictable, CD4-count-dependent hierarchy. This is the conceptual backbone of the entire lecture.

Three phases ^[1]:

Natural history graph landmarks (from the classic Pantaleo/Fauci curve shown in slides) ^[1]:

• Primary infection (weeks 0–12): CD4 drops from ~1000 to ~500; HIV RNA spikes to a sharp peak at ~6 weeks, then falls as immune response develops
• Clinical latency (years 1–8): CD4 gradually declines (~600 → 200); HIV RNA remains low but trends upward
• Constitutional symptoms appear around years 7–8 as CD4 approaches ~200
• Opportunistic diseases emerge around years 9–10 (CD4 < 100)
• Death occurs around year 11 without treatment, with near-zero CD4 and steeply rising viral load

Historical/untreated natural history: the curve is not a prognosis for a person receiving effective modern ART. Without treatment, about half of people in the historical cohorts progressed to AIDS within roughly 10 years; effective ART suppresses viral replication, permits immune recovery, and radically changes this trajectory. ^[1]

The slides deliberately move from a global view to Hong Kong, but their figures come from different reporting years and should not be quoted as current totals:

• 2020 UNAIDS snapshot: 37.7 million people living with HIV, 1.5 million new infections and 680,000 AIDS-related deaths. ^[1]
• 2010–2022 trend map: new infections fell globally by 38%, with the steepest falls in eastern/southern Africa (57%) and western/central Africa (49%), but increased in eastern Europe/central Asia (49%), the Middle East/north Africa (61%) and Latin America (8%). These regional trends explain why “global decline” can obscure expanding local epidemics. ^[1]
• Treatment-impact model: ART was estimated to have averted 20.8 million AIDS-related deaths from 1996–2022. ^[1]
• 2020 acquisition distribution: the pie charts compare sub-Saharan Africa with the rest of the world; proportions attributed to gay men/other MSM, people who inject drugs, sex workers, clients/partners and transgender women vary substantially by region. These are population-attribution estimates, not inherent risks attached to identities. Transmission biology depends on exposure, viral load and prevention access. ^[1]

HIV incidence in Hong Kong: the lecture poses "increasing or decreasing?" The slide graph is a 1984–2023 historical snapshot: annual diagnoses rose to a peak of 725 in 2015, then fell to 397 in 2023. Current official surveillance reports 331 new HIV diagnoses in 2025, the tenth consecutive annual decline; these are notifications, not a direct measure of incidence. ^[1][11]

Most commonly reported exposure category in the lecture/current HK data: sexual contact, with homosexual/bisexual contact the largest specified category. “MSM” describes a population, not a biological route; the route is sexual exposure. ^[1][11]

Lecture snapshot (through 2023) ^[1]:

• Cumulative notifications: 12,038 HIV / 2,483 AIDS (1984–2023)
• The graph shows 725 HIV notifications at the 2015 peak, then a decline to 397 in 2023; the contemporaneous AIDS count was 101 in 2023.
• HIV clinic services in HK: Princess Margaret Hospital (HA), Queen Elizabeth Hospital (HA), Kowloon Bay Integrated Centre (DH)
• 90-90-90 is the historical cascade target shown in the lecture. The current UNAIDS target referenced by Hong Kong's 2024 testing recommendations is 95-95-95. ^[24]

Current surveillance check (through 2025): Hong Kong recorded 331 HIV and 86 AIDS notifications in 2025, bringing the cumulative totals since 1984 to 12,734 HIV and 2,643 AIDS notifications. Among 2025 HIV notifications, 158 were attributed to homosexual/bisexual contact and 121 to heterosexual contact; 48 were undetermined. Use current DH figures for contemporary questions, but retain the slide values when a question explicitly asks about the lecture dataset. ^[11]

2021 HK demographic profile (CHP Factsheet) ^[1]:

• Male: 82.1% | Chinese: 70.7% | Age 20–49: 71.4%
• Route of transmission: sexual contact 80.8% (homosexual 43.6%, heterosexual 27.3%, bisexual 9.8%), IVDU 0.7%, blood contact/perinatal 0%

Three commonest AIDS-defining illnesses in HK (1985–2021, N = 2,280) ^[1]:

Clinical scenario: M/40, lorry driver. 1 week of fever, myalgia, malaise, faint rash over trunk and limbs. Examination: shotty cervical lymph nodes, maculopapular non-itchy rash. ^[1]

Investigations: NPA flu/COVID negative, WCC 5.6 with atypical lymphocytes, Monospot positive. History reviewed → commercial sex in China. ^[1]

Anti-HIV Ab: indeterminate. HIV RNA: positive. → Impression: Acute seroconversion of HIV ^[1]

Acute HIV infection (acute retroviral syndrome) key teaching points from the slide ^[1]:

• Usual onset 2-4 weeks after exposure
• Mononucleosis-like illness in 50-60%: fever, pharyngitis, lymphadenopathy, rash, headache
• Lasts 10-15 days
• Lab: mild anaemia, thrombocytopenia, raised ALT, atypical lymphocytes
• Clinical implications:
  1. Do not rely on a repeat antibody-only test when acute HIV is suspected: obtain a laboratory Ag/Ab test and HIV-1 NAT
  2. Initiation of ART recommended for confirmed infection
  3. Prevention of transmission (patient is highly infectious during acute phase due to massive viremia)

These are conditions that should prompt an HIV test ^[1]:

• Unexplained generalised lymphadenopathy
• Unexplained weight loss
• Idiopathic thrombocytopenia
• Herpes zoster (especially in young patients)
• Oral candidiasis
• Severe bacterial infections (e.g., invasive pneumococcal disease)

"Offer HIV test when you encounter these conditions" — direct slide quote. ^[1]

Full CDC list of AIDS-defining (Stage 3) illnesses (from slides) ^[1]:

• Bacterial infections, multiple or recurrent
• Candidiasis of bronchi, trachea, or lungs
• Candidiasis of oesophagus
• Cervical cancer, invasive
• Coccidioidomycosis, disseminated or extrapulmonary
• Cryptococcosis, extrapulmonary
• Cryptosporidiosis, chronic intestinal (> 1 month)
• CMV disease (other than liver, spleen, or nodes), onset age > 1 month
• CMV retinitis (with loss of vision)
• Encephalopathy attributed to HIV
• Herpes simplex: chronic ulcers (> 1 month) or bronchitis, pneumonitis, or oesophagitis
• Histoplasmosis, disseminated or extrapulmonary
• Isosporiasis, chronic intestinal (> 1 month)
• Kaposi sarcoma
• Lymphoma: Burkitt, immunoblastic, or primary CNS
• Mycobacterium avium complex or M. kansasii, disseminated or extrapulmonary
• Mycobacterium tuberculosis, any site (pulmonary, disseminated, or extrapulmonary)
• Pneumocystis jirovecii pneumonia
• Pneumonia, recurrent
• Progressive multifocal leukoencephalopathy
• Salmonella septicaemia, recurrent
• Toxoplasmosis of brain
• Wasting syndrome attributed to HIV

AIDS = CD4 < 200 cells/mm³ AND/OR presence of AIDS-defining conditions (CDC list) ^[1]

Prior to ART, median survival from AIDS diagnosis ≈ 20 months ^[1]

This is extremely high-yield for exams. The lecture figure correlates CD4 strata with typical OIs ^[1][2]:

Hong Kong practice (SCAS, November 2024) retains the two-step framework shown in the lecture ^[24]:

1. Screen with a laboratory assay; most Hong Kong laboratories use a fourth-generation HIV Ag/Ab combination assay.
2. Submit every positive or equivocal screen for confirmatory laboratory testing. The local guidance names either Western blot or an HIV-1/HIV-2 antibody differentiation immunoassay; the latter is increasingly used because it is faster and distinguishes HIV-2 more readily.
3. Use a molecular test when diagnostic uncertainty remains. Repeat testing after an indeterminate result, recent exposure within three months, or whenever clinically indicated.
4. If acute HIV is suspected despite a non-reactive or equivocal serological result, obtain HIV RNA/NAT urgently rather than waiting for antibody seroconversion.

International comparison: the CDC/APHL algorithm is more prescriptive: Ag/Ab assay → HIV-1/HIV-2 differentiation assay → HIV-1 NAT when the differentiation assay is non-reactive or indeterminate. In that algorithm, a reactive NAT identifies acute HIV-1, whereas a non-reactive NAT usually indicates a false-reactive screen. ^[12]

Practical window periods in the absence of antiretroviral drugs ^[13][24]:

The lecture references Sullivan et al. (PLoS One 2013) — certain indicator conditions should prompt routine HIV testing regardless of perceived risk. The slide highlights three conditions with the highest HIV prevalence in the study ^[1]:

Other indicator conditions tested: malignant lymphoma, cervical/anal dysplasia or cancer, herpes zoster, hepatitis B or C, seborrhoeic dermatitis. ^[1]

Scenario: M/35 with history of herpes zoster at age 28. 1 month low-grade fever, dry cough, decreased exercise tolerance, SOB on exertion. TOCC negative. ^[1]

Imaging pattern: The frontal/lateral radiographs show bilateral, relatively symmetrical perihilar/interstitial opacity without a pleural effusion or obvious cardiomegaly. The CT then reveals extensive ground-glass opacity plus multiple thin-walled cysts/pneumatoceles. Cystic PCP carries a pneumothorax risk; conversely, spontaneous pneumothorax in a person with HIV should raise suspicion for PCP. A normal early radiograph does not exclude PCP. ^[1][14]

Investigations: WCC 2.1, lymphocyte 0.3, CRP 9.8, sputum C/ST commensals, AFB smear negative. Given Augmentin + azithromycin → persistent fever, oxygen desaturation. ^[1]

Sputum induction → Pneumocystis jirovecii present. Anti-HIV positive. CD4: 45. ^[1]

PCP key facts ^[1]:

• Caused by Pneumocystis jirovecii, classified as fungus but shares biologic characteristics with protozoa
• 90% of cases occur when CD4 < 200 cells/mm³
• Clinical triad: chronic dry cough, SOB on exertion, fever
• CXR: diffuse, bilateral, symmetrical interstitial infiltrates from hila
• Diagnosis: induced sputum or BAL with specific staining/immunofluorescence or PCR; serum beta-D-glucan is sensitive supportive evidence but is not organism-specific
• Treatment: high-dose TMP-SMX for 21 days; add corticosteroids for room-air PaO₂ < 70 mmHg or A–a gradient ≥35 mmHg, ideally within 72 hours of starting PCP therapy ^[14]

Scenario: M/58, HT/DM, 1 month dysphagia, no vomiting, weight loss. WCC 4.5, lymphocyte 0.5. ^[1]

OGD: The endoscopic image shows widespread adherent white plaque-like lesions throughout the oesophagus; biopsy confirmed Candida. The accompanying oral photograph shows scrapable white plaques compatible with thrush. ^[1]

History reviewed: a remote commercial sexual exposure was elicited. Anti-HIV positive, CD4: 85. ^[1]

Treatment: systemic fluconazole plus ART ^[1]

Why this matters: Oesophageal candidiasis is an AIDS-defining illness (unlike oral candidiasis alone). It typically causes dysphagia and/or odynophagia at advanced immunosuppression. Oral thrush supports the diagnosis but can be absent. Empiric systemic fluconazole is often appropriate; endoscopy is especially useful when symptoms are atypical or fail to improve, when CMV/HSV ulceration or malignancy enter the differential. ^[15]

Scenario: M/36, Thai, 4 years in HK. 2 months of generalised non-itchy skin rash, fever, weight loss. ^[1]

Examination: Febrile, cervical and groin lymph nodes, erythematous papules over 4 limbs and face, some being 'umbilicated', liver edge palpable. ^[1]

Blood culture: Penicillium marneffei (now Talaromyces marneffei). The slide records prior injection drug use and an HIV diagnosis six years earlier followed by loss to follow-up and no treatment. ^[1]

Penicilliosis/Talaromycosis key facts ^[1]:

• Caused by dimorphic fungus Talaromyces marneffei (formerly Penicillium marneffei)
• Endemic in Southeast Asia (especially Northern Thailand and Vietnam) and southern China
• Clinical triad: fever, anaemia, weight loss
• Characteristic visual clue: generalised papules with central umbilication/necrosis resembling molluscum contagiosum; this is highly suggestive in the right epidemiological setting but not pathognomonic
• Diagnosis: blood fungal culture, bone marrow culture
• Treatment: liposomal amphotericin B IV for 2 weeks → itraconazole 200 mg twice daily for 10 weeks (consolidation) → itraconazole 200 mg daily (maintenance) until immune recovery ^[16]
• CD4 at presentation in this case: 14

At entry into care ^[1]:

• CD4 T-cell count
• Plasma HIV RNA (viral load)
• CBC, chemistry profile, ALT, BUN, creatinine, urinalysis
• Serologies for hepatitis A, B, and C
• Fasting blood glucose and serum lipids
• Genotypic resistance testing

Also assess pregnancy where relevant, TB and STI risk/testing, vaccination history, and medication interactions; obtain HLA-B*5701 only if abacavir is being considered. Baseline results guide regimen choice, but ART generally should not be delayed while every result is pending. ^[17]

Why each matters:

• CD4 + viral load = staging and treatment urgency
• Hep A/B/C = co-infection management (shared transmission routes); Hep B has overlapping NRTI therapy (tenofovir, lamivudine)
• Glucose/lipids = ART side effects (metabolic syndrome) and cardiovascular risk
• Resistance testing = guides initial regimen choice

“HAART” is the historical slide term. Modern guidance generally uses combination antiretroviral therapy (ART) because effective therapy is now standard, not a special “highly active” subset.

Six drug classes ^[1]:

The lecture walks through the evolution from 1981 (AIDS first reported) to modern single-tablet regimens ^[1]:

The paradigm shift: Potent ART → Less side effects → Simplified → Less frequent drug administration ^[1]

Pill burden evolution ^[1]:

Five goals ^[1]:

1. Maximally suppress plasma HIV viral load
2. Restore and preserve immunological function
3. Reduce HIV-related morbidity and mortality
4. Improve quality of life
5. Prevent vertical transmission in women of childbearing potential

U=U: A person taking ART who achieves and maintains viral suppression (HIV RNA < 200 copies/mL) has effectively no risk of sexually transmitting HIV. U=U does not prevent other STIs, and it should not be extrapolated to occupational blood exposures. ^[18]

ART is recommended for ALL persons with HIV to reduce morbidity and mortality (AI) and to prevent transmission (AI). ART should be initiated immediately (or as soon as possible) after HIV diagnosis to increase uptake, decrease time to viral suppression, and improve virologic suppression rates (AII). ^[1]

Evidence rating key: A = Strong recommendation; I = Randomised controlled trial data; II = Well-designed observational data; III = Expert opinion. ^[1]

Current NIH recommended initial regimens for most people without prior long-acting cabotegravir PrEP exposure are ^[17]:

• Bictegravir/TAF/FTC (single tablet), or
• Dolutegravir + TAF or TDF + FTC or 3TC, or
• Dolutegravir/3TC in selected people.

DTG/3TC exceptions: do not use as rapid-start therapy before HBV serology, reverse-transcriptase genotype and viral load are available; avoid with HBV coinfection or HIV RNA above 500,000 copies/mL. The slide’s DTG/ABC/3TC regimen now sits in “certain clinical scenarios,” rather than the preferred-for-most list, because it requires HLA-B*5701 testing and abacavir has other limitations. Prior CAB-LA PrEP exposure changes the resistance assessment and empiric regimen. ^[17]

Injectable ART: Cabotegravir + rilpivirine IM every 2 months for virologically suppressed patients — a major advance in convenience and adherence. ^[1]

Patient-reported advantages of injectable CAB + RPV LA (CARISEL study, n=275) ^[1]:

• 81% agreed it is less stigmatising than daily oral medications
• 71% reported less adherence anxiety (no daily pill reminder)
• 67% reported not having to think about HIV status every day

Risk increases with ^[1]:

• Higher viremia
• Receptive anal intercourse (highest per-act risk)
• Presence of other STDs (especially genital ulcers)

Strategies ^[1]:

• Condoms and individualized, non-judgmental risk-reduction/harm-reduction support
• Male circumcision (reduces heterosexual female-to-male transmission)
• Diagnose and treat other STIs
• ART for the HIV-positive partner (treatment as prevention / U=U)
• Pre-exposure prophylaxis (PrEP)

Without intervention: risk 15-40% ^[1]

• Transmission can occur in utero, intrapartum, and postpartum (breastfeeding)

Strategies ^[1]:

• HIV testing for all pregnant women (universal antenatal screening)
• Effective antenatal/intrapartum/postpartum ART
• Scheduled Caesarean birth only when indicated by viral load
• Infant ARV management and patient-centred infant-feeding counselling

PrEP = use of ARVs to prevent HIV acquisition in people without HIV who may be exposed. Hong Kong guidance considers it as part of combination prevention for people with elevated ongoing risk, assessed case by case; U.S. CDC guidance additionally recommends prescribing PrEP to anyone who asks after confirming HIV-negative status. ^[21][25]

Strategies ^[1]:

1. Daily oral PrEP: TDF/3TC (or TDF/FTC)
   • Maximum protective drug levels are reached after about 7 days for receptive anal sex and up to 21 days for receptive vaginal sex or injection-drug exposure; onset data are insufficient for insertive sex.
2. Event-driven PrEP (2+1+1): 2 pills 2-24 hours before sex → 1 pill 24h after → 1 pill 48h after
   • IPERGAY trial: TDF-FTC before and after sexual activity provided 86% relative risk reduction in HIV acquisition among MSM ^[1]
   • Use F/TDF only. This has been studied in adult gay/bisexual men; it is off-label in the United States, is not CDC-recommended, and should be avoided in active HBV because episodic tenofovir withdrawal can precipitate hepatitis flares. Follow the relevant local protocol. ^[21]
3. Injectable PrEP: cabotegravir IM, with a second dose one month after the first and then every two months; timely injections and ongoing HIV Ag/Ab plus RNA testing are essential. ^[21]

Hong Kong monitoring points: obtain a negative laboratory fourth-generation test within seven days before oral PrEP initiation, do not use a lower-sensitivity point-of-care test for this purpose, check renal and hepatitis status, screen/treat STIs, and arrange follow-up at intervals of no more than three months. On-demand PrEP should not be used in chronic HBV. ^[25]

Key trial evidence for PrEP ^[1]:

• iPrEx trial (daily oral FTC-TDF in MSM): 44% relative risk reduction vs placebo (P = 0.005)
• IPERGAY trial (event-driven TDF-FTC in MSM): 86% relative risk reduction vs placebo (P = 0.002); incidence 0.91 vs 6.6 per 100 person-years

The iPrEx graph reports the overall trial effect, not a 44% biological ceiling: protection depended strongly on actually taking the medication. This is why adherence assessment is central to PrEP follow-up. ^[25]

Historical average transmission estimates from an untreated viremic source ^[1]:

• 0.33% following percutaneous exposure (needlestick/sharps injury)
• 0.09% following mucosal exposure
• 0% following intact skin exposure — intact skin is an effective barrier; contamination of intact skin is NOT considered an exposure

Risk is modified by depth, hollow-bore needle, visible blood, whether the device was in an artery/vein, source viral load and other factors. These percentages are not a calculator for an individual exposure.

Infectious ^[1]:

• Blood, semen, vaginal secretions, other fluids contaminated with visible blood
• Potentially infectious (undetermined risk): CSF, synovial, pleural, peritoneal, pericardial, amniotic fluid

NOT considered infectious (unless blood-contaminated) ^[1]:

• Faeces, nasal secretions, saliva, gastric secretions, sputum, sweat, tears, urine, vomitus

Intact skin is an effective barrier against HIV. Contamination of intact skin is NOT considered an exposure. ^[1]

Immediate steps ^[1]:

1. Stop safely and report the exposure immediately
2. Immediate cleansing of the exposed site
   • Skin: wash with soap and water
   • Eyes: irrigate with clean water, saline, or sterile irrigant; other mucosa: flush with water
   • Do not squeeze the wound or apply caustic agents; antiseptics have not been shown to reduce transmission risk
3. Clinical documentation: details of the exposure, source patient status, recipient HCP details
4. Urgent risk assessment for HIV PEP and separate HBV/HCV management; wound care and blood tests must not delay the first indicated PEP dose ^[22][23]

Current Hong Kong guidance (SCAS, December 2025) ^[27]:

• Obtain a baseline laboratory HIV test before PEP, plus renal/liver function and a pregnancy test where relevant; also assess HBV/HCV exposure. Do not delay the first PEP dose while waiting for results.
• Follow-up HIV antibody testing is normally performed at 3–6 months. Test earlier if acute retroviral symptoms occur or if required for clinical assessment/anxiety, but an early negative result does not end follow-up.
• Counsel the exposed person to report fever, rash or a mononucleosis-like illness promptly and to avoid blood/tissue/semen donation until infection has been excluded.

Why another schedule may appear online: the 2025 U.S. Public Health Service guideline instead uses final laboratory Ag/Ab plus NAT at week 12, with a selective interim Ag/Ab plus NAT at weeks 4–6 when PEP began more than 24 hours after a single exposure or doses were missed. Follow the protocol of the treating Hong Kong service rather than mixing schedules. ^[23][27]

Current Hong Kong approach: use a three-drug regimen ^[27]:

• preferred NRTI backbone: TDF/FTC or TDF/3TC
• add an integrase inhibitor such as raltegravir or dolutegravir; fixed-dose BIC/FTC/TAF is also an acceptable lower-pill-burden option where appropriate and available

Check renal/hepatic function, pregnancy, interactions and known source resistance; seek HIV-expert input for complex cases without delaying the first dose. International regimen tables differ: the 2025 U.S. guideline lists BIC/FTC/TAF or DTG plus a tenofovir/FTC-or-3TC backbone as preferred and no longer places raltegravir in its preferred table because of pill burden. ^[23][27]

Timing: start as soon as possible, preferably within 1–2 hours, and do not wait for source results. Benefit after 72 hours is unlikely; Hong Kong guidance reserves later initiation for exceptional cases where specialist assessment finds benefit likely to outweigh risk. ^[27]

Duration: 28 days ^[1]

Starter kit available in AED ^[1]

Referred to staff clinic / regional post-exposure HIV clinic for follow-up ^[1]

• 2020 SAQ Q10: Penile ulcer, multiple sexual partners → STD workup including HIV; safe sex counselling ^[5]
• 2024 SAQ Q12(f): Three viruses transmitted by blood products → HIV, HBV, HCV ^[6]