Microbiology chapters
HIV
Human immunodeficiency virus: its structure and genes, how it enters and replicates in CD4 cells, how it spreads (and the situation in Pakistan), the stages from acute infection to AIDS, opportunistic infections by CD4 count, testing (antibody/antigen tests, PCR, viral load) and the basics of treatment and prevention.
- HIV is an enveloped retrovirus (lentivirus) with two copies of +ssRNA, reverse transcriptase, integrase and protease; its envelope gp120 binds CD4 (on helper T cells, macrophages, dendritic cells) with a co-receptor (CCR5 early, CXCR4 later), gp41 mediates fusion, and the core protein p24 is used in early antigen tests; reverse transcriptase makes DNA, which integrates as a provirus (lifelong latent reservoir), and HIV mutates rapidly.
- Spread by sex, blood (transfusion, shared or reused needles and syringes: the cause of Pakistan's 2019 Larkana (Ratodero) outbreak among children) and mother to child (pregnancy, delivery, breastfeeding); after acute retroviral syndrome (flu-like, rash, lymphadenopathy, 2–4 weeks) comes a long clinically latent phase with falling CD4, then AIDS (CD4 below 200/µL or an AIDS-defining illness): Pneumocystis pneumonia (<200), toxoplasmosis and cryptococcal meningitis (<100), CMV retinitis and MAC (<50), Kaposi sarcoma (HHV-8), TB at any CD4.
- Diagnosis: antibody/antigen (p24) 4th-generation ELISA or rapid tests (screening; the window period is shortest with antigen and PCR tests), confirmed by a second assay; HIV DNA/RNA PCR for babies (maternal antibody persists up to 18 months); viral load monitors treatment and CD4 shows immune status; ART (e.g. tenofovir + lamivudine + dolutegravir) for everyone, plus PEP within 72 hours and PMTCT.
On this page
The virus
- Retrovirus (lentivirus subfamily); HIV-1 causes most infection worldwide; HIV-2 (West Africa) is less virulent.
- Enveloped, with two identical copies of single-stranded positive-sense RNA.
- Carries reverse transcriptase (RNA → DNA; no proofreading → high mutation rate), integrase and protease.
Structure and genes
| Gene | Product | Role |
|---|---|---|
| gag | p24 (capsid), p17 (matrix), p7 | Core proteins; p24 antigen is detected in early infection |
| pol | Reverse transcriptase, integrase, protease | Enzymes (all drug targets) |
| env | gp160 → gp120 + gp41 | gp120: binds CD4 and co-receptor (hypervariable: vaccine problem); gp41: membrane fusion (enfuvirtide target) |
| tat | Transactivator | Increases transcription |
| rev | Regulator | mRNA export from nucleus |
| nef | Negative factor | Reduces MHC class I and CD4 on infected cells |
| vif, vpr, vpu | Accessory | Counteract host defences (vif blocks APOBEC3G) |
Life cycle
- Attachment: gp120 binds CD4 on helper T cells, macrophages, dendritic cells and microglia.
- Co-receptor binding: CCR5 (macrophage-tropic strains: usually transmitted and early) or CXCR4 (T-cell-tropic strains: later, faster decline). People homozygous for CCR5 Δ32 are largely resistant (maraviroc blocks CCR5).
- Fusion of envelope and membrane (gp41), entry of the core.
- Reverse transcription: RNA → double-stranded DNA (in the cytoplasm).
- Integration: DNA enters the nucleus and integrase inserts it into the host genome as a provirus (permanent; latent reservoir in resting memory T cells explains why ART cannot cure).
- Transcription and translation by host machinery (activated by tat when the cell is activated).
- Assembly, budding from the membrane, and maturation (viral protease cleaves gag-pol polyproteins: needed for infectious virions).
Each step is a drug target: entry (maraviroc, enfuvirtide), reverse transcriptase (NRTIs, NNRTIs), integrase (dolutegravir), protease (lopinavir, darunavir).
Transmission
| Route | Notes |
|---|---|
| Sexual | The commonest route worldwide; risk higher with receptive anal sex, other STIs (genital ulcers), high viral load |
| Blood | Transfusion of unscreened blood (very high risk per exposure), sharing needles (IV drug use), unsafe medical injections and reused syringes, dialysis and dental equipment, needlestick injury (about 0.3% per exposure, much lower than hepatitis B) |
| Mother to child | During pregnancy, delivery (most) and breastfeeding; without intervention a substantial share of babies are infected; with ART for the mother and prophylaxis for the baby, the risk falls to very low levels |
| Not spread by | Casual contact, hugging, sharing food or toilets, mosquitoes, saliva or tears in normal circumstances |
Pakistan: HIV is concentrated in people who inject drugs, transgender people and sex workers and their partners, and through unsafe injections. In 2019, an outbreak in Ratodero, Larkana (Sindh) infected hundreds of people, mostly children, linked to reuse of syringes and unsafe medical practice. Prevention therefore includes safe injection practices and auto-disable syringes.
Natural history
- Acute (primary) HIV infection (2–4 weeks after exposure): acute retroviral syndrome in many: fever, sore throat, maculopapular rash, lymphadenopathy, myalgia, mouth ulcers (like glandular fever); very high viral load (very infectious); CD4 falls temporarily; antibody tests may still be negative (window period).
- Seroconversion: antibodies appear (usually within about 3–12 weeks).
- Clinical latency (asymptomatic phase): typically years (average about 8–10 years without treatment); persistent generalised lymphadenopathy; virus keeps replicating in lymphoid tissue; CD4 falls steadily (roughly 50–100 cells/µL per year); viral load set point predicts speed of progression.
- Symptomatic HIV: oral thrush, oral hairy leukoplakia (EBV), herpes zoster, recurrent bacterial infections, weight loss, chronic diarrhoea, fever.
- AIDS: CD4 below 200 cells/µL or an AIDS-defining illness; death within about 2 years without treatment.
CD4 count (normal about 500–1,500 cells/µL) shows immune damage and decides prophylaxis; viral load (HIV RNA copies/mL) shows replication, infectiousness and treatment response.
Opportunistic infections and tumours by CD4 count
| CD4 (cells/µL) | Conditions |
|---|---|
| Any level (more as CD4 falls) | Tuberculosis (the commonest serious opportunistic infection and leading cause of death in people with HIV in Pakistan and similar settings), bacterial pneumonia (pneumococcus), herpes zoster, oral candidiasis, Kaposi sarcoma |
| Below 200 | Pneumocystis jirovecii pneumonia (dry cough, breathlessness, hypoxia on exertion, bilateral interstitial shadows; silver stain; co-trimoxazole treatment and prophylaxis), oesophageal candidiasis, HIV encephalopathy and dementia, progressive multifocal leukoencephalopathy (JC virus), Kaposi sarcoma (more common), cryptosporidiosis |
| Below 100 | Cerebral toxoplasmosis (multiple ring-enhancing brain lesions; prophylaxis with co-trimoxazole), cryptococcal meningitis (India ink, CrAg antigen; amphotericin + flucytosine, then fluconazole), histoplasmosis |
| Below 50 | CMV retinitis ("pizza pie" fundus; ganciclovir), CMV colitis and oesophagitis, disseminated Mycobacterium avium complex (fever, weight loss, anaemia; azithromycin prophylaxis), primary CNS lymphoma (EBV; single ring-enhancing lesion) |
AIDS-related cancers: Kaposi sarcoma (HHV-8; purple skin and mucosal lesions), non-Hodgkin lymphoma (EBV; including primary CNS lymphoma), invasive cervical cancer (HPV).
PCP < 200 → Toxo and Crypto < 100 → CMV and MAC < 50. TB occurs at any CD4.
Laboratory diagnosis
| Test | Use |
|---|---|
| 4th-generation ELISA (antibody + p24 antigen) | Standard screening; detects infection about 2–4 weeks after exposure (shorter window than antibody-only tests) |
| Rapid diagnostic tests | Point-of-care screening; Pakistan uses a 3-test algorithm (positive results confirmed with different assays) |
| Western blot / line immunoassay | Older confirmatory tests (antibodies to p24, gp41, gp120); largely replaced |
| HIV RNA PCR (viral load) | Very early infection (before antibodies), monitoring ART (target: undetectable) |
| HIV DNA PCR | Infants under 18 months (maternal IgG crosses the placenta and can persist up to 18 months, so antibody tests cannot be used) |
| CD4 count (flow cytometry) | Staging, prophylaxis decisions |
| Resistance testing | Genotype before treatment or on failure |
Window period: the time after infection when tests are still negative; repeat testing after exposure (for example at 6 weeks and 3 months).
Treatment and prevention
- ART for everyone with HIV, as soon as possible, regardless of CD4 count ("test and treat").
- Preferred first-line regimen: TLD (tenofovir + lamivudine + dolutegravir); combinations of three drugs from at least two classes prevent resistance.
- Undetectable = untransmittable: a person with a suppressed viral load does not transmit HIV sexually.
- Co-trimoxazole prophylaxis (PCP, toxoplasma); TB preventive therapy; vaccinations; screening for TB, hepatitis B and C, cryptococcal antigen (CD4 < 200).
- Post-exposure prophylaxis (PEP): within 72 hours (ideally within hours) of exposure, 3 drugs for 28 days.
- Pre-exposure prophylaxis (PrEP): tenofovir-based for people at high risk.
- PMTCT: test all pregnant women; lifelong ART for the mother; infant prophylaxis (nevirapine ± zidovudine); safe delivery; infant feeding counselling; early infant diagnosis by PCR.
- Safe blood (screening), safe injections (auto-disable syringes), harm reduction for people who inject drugs (needle exchange, opioid substitution), condoms, STI treatment, voluntary medical male circumcision.
- No effective vaccine yet (gp120 variability).
CD4 count = total WBC × % lymphocytes × % CD4 cells (of lymphocytes)
WBC 4,000/µL, lymphocytes 25%, CD4 10% of lymphocytes:
lymphocytes = 4,000 × 0.25 = 1,000/µL
CD4 = 1,000 × 0.10 = 100 cells/µL → AIDS (< 200)
Prophylaxis needed: co-trimoxazole (PCP < 200, toxoplasma < 100)
Not yet below 50 → MAC prophylaxis not routinely needed once ART starts
Expect: HIV structure and genes (gag, pol, env), gp120 and gp41 roles, p24, CD4 and co-receptors (CCR5 Δ32), life cycle steps and drug targets, transmission routes and Pakistan's unsafe-injection outbreak, acute retroviral syndrome, natural history, CD4 vs viral load, AIDS definition, opportunistic infections by CD4 threshold, Kaposi sarcoma and HHV-8, TB at any CD4, diagnostic tests (4th-generation ELISA, rapid tests, PCR in infants, window period), ART basics, PEP timing and duration, PMTCT.
Quick revision
- Retrovirus: 2 copies +ssRNA, reverse transcriptase, integrase, protease.
- gp120 binds CD4; CCR5/CXCR4 co-receptors; gp41 fusion; p24 capsid.
- Spread: sex, blood (reused syringes: Larkana 2019), mother to child.
- Acute retroviral syndrome → long latency → AIDS (CD4 < 200).
- PCP < 200; toxoplasma, cryptococcus < 100; CMV, MAC < 50; TB at any CD4.
- 4th-gen ELISA (antibody + p24); infants: DNA PCR; viral load monitors ART.
- ART for all (TLD); PEP within 72 h for 28 days; PMTCT.
Written by The House Job from standard microbiology references (Levinson's Review of Medical Microbiology and Immunology).
FAQ
Which receptor and co-receptors does HIV use?
The CD4 molecule, together with the chemokine co-receptors CCR5 (early infection) or CXCR4 (later).
At what CD4 count is AIDS defined?
Below 200 cells/µL, or when an AIDS-defining illness develops, whatever the count.
Why is PCR used to diagnose HIV in infants?
Maternal antibodies cross the placenta and can persist for up to 18 months, so antibody tests cannot tell whether the baby itself is infected.
Which opportunistic infections occur below a CD4 count of 50?
CMV retinitis and disseminated Mycobacterium avium complex, along with primary CNS lymphoma.