Medicine chapters
HIV and opportunistic infections
How HIV is diagnosed, how the CD4 count predicts which opportunistic infections appear, how to recognise and treat the common ones, and the basics of antiretroviral therapy, prophylaxis and PEP.
- HIV is a retrovirus that destroys CD4 T cells; untreated, the CD4 count falls over years until opportunistic infections and tumours (AIDS) appear.
- Diagnose with a 4th-generation antibody plus p24 antigen test, confirm, then measure CD4 count and viral load; each infection appears below a typical CD4 threshold (PCP below 200, toxoplasma below 100, CMV and MAC below 50).
- Start ART for everyone as soon as ready (usually two NRTIs plus dolutegravir), give co-trimoxazole prophylaxis when CD4 is low, and delay ART a few weeks in cryptococcal and TB meningitis to reduce IRIS.
On this page
Overview
HIV (human immunodeficiency virus) causes a slow, progressive loss of CD4 helper T cells. Without treatment this leads to AIDS: life-threatening opportunistic infections and cancers.
With modern antiretroviral therapy (ART), people with HIV can live a near-normal life span, and those with an undetectable viral load do not transmit HIV sexually ("U = U"). In Pakistan HIV is concentrated in key populations (people who inject drugs, sex workers, transgender people) but outbreaks have also followed unsafe injections and reuse of needles in healthcare settings.
The virus
- Retrovirus (genus Lentivirus). Two types: HIV-1 (worldwide) and HIV-2 (mostly West Africa, slower course; some drugs such as NNRTIs do not work on it).
- Carries reverse transcriptase, which copies viral RNA into DNA; integrase inserts it into the host genome; protease cuts viral proteins into working form. Each enzyme is a drug target.
- gp120 binds the CD4 molecule and a co-receptor (CCR5 or CXCR4); gp41 mediates fusion.
- Reverse transcription makes many errors, so the virus mutates fast and resistance develops if treatment is incomplete.
People homozygous for the CCR5-delta32 deletion are highly resistant to infection with CCR5-using HIV strains.
Transmission
- Sexual (commonest worldwide), blood (transfusion, shared needles, unsafe injections), mother to child (pregnancy, delivery, breastfeeding).
- Not spread by casual contact, sharing food or mosquitoes.
Natural history
| Stage | Features |
|---|---|
| Acute (primary) HIV / seroconversion illness | 2–6 weeks after exposure; glandular-fever-like illness: fever, sore throat, lymphadenopathy, maculopapular rash, mouth ulcers, myalgia, aseptic meningitis. Very high viral load, very infectious |
| Clinical latency | Years (often about 10) without symptoms; CD4 count falls steadily; persistent generalised lymphadenopathy may be present |
| Symptomatic HIV | Oral thrush, oral hairy leukoplakia, shingles, weight loss, diarrhoea, fevers |
| AIDS | CD4 below 200 cells/mm3 or an AIDS-defining illness |
In the window period (early weeks), antibody tests can be negative. Repeat testing; viral RNA (PCR) and p24 antigen turn positive first.
Diagnosis
- Screening: 4th-generation ELISA (detects HIV antibody and p24 antigen together) or rapid tests.
- Confirmation: a second, different assay (national algorithms use two or three different rapid tests or an immunoassay plus confirmatory test).
- Baseline work-up after diagnosis:
- CD4 count (degree of immune damage; guides prophylaxis).
- HIV viral load (RNA PCR; baseline and to monitor ART).
- Resistance testing where available; HLA-B*5701 before abacavir.
- Screen for TB, hepatitis B and C, syphilis, cryptococcal antigen if CD4 is low.
- FBC, renal and liver function, lipids, glucose, urine protein.
- Infants of infected mothers need HIV DNA/RNA PCR, because maternal IgG antibodies cross the placenta and persist for up to 18 months.
The CD4 count shows how damaged the immune system is; the viral load shows how well treatment is working.
Opportunistic infections by CD4 count
| CD4 count (cells/mm3) | Typical problems |
|---|---|
| Any count | TB (pulmonary), bacterial pneumonia (pneumococcus), shingles, oral candida, Kaposi sarcoma |
| Below 200 | Pneumocystis pneumonia (PCP), oesophageal candidiasis, cryptococcal disease, extrapulmonary TB, HIV dementia |
| Below 100 | Cerebral toxoplasmosis, cryptosporidiosis, microsporidiosis, cryptococcal meningitis, PML |
| Below 50 | CMV retinitis and colitis, disseminated Mycobacterium avium complex (MAC), primary CNS lymphoma |
Pneumocystis jirovecii pneumonia (PCP)
- Insidious onset over weeks: dry cough, progressive exertional breathlessness, fever.
- Chest often clear; desaturation on exercise is typical.
- CXR: bilateral perihilar interstitial ("ground-glass") shadowing; may be normal early. HRCT shows ground-glass change. Pneumothorax can occur.
- Diagnosis: organisms on induced sputum or bronchoalveolar lavage with silver stain or immunofluorescence, or PCR. The fungus cannot be cultured.
- Treatment: high-dose co-trimoxazole for 21 days; add prednisolone if hypoxic (PaO2 below 8 kPa) to reduce deaths. Alternatives: IV pentamidine, clindamycin plus primaquine, atovaquone.
- Prophylaxis: co-trimoxazole when CD4 is below 200.
Cerebral toxoplasmosis
- Reactivation of Toxoplasma gondii; CD4 usually below 100.
- Headache, fever, confusion, focal signs, seizures.
- CT/MRI: multiple ring-enhancing lesions, often in the basal ganglia, with oedema.
- Toxoplasma IgG usually positive.
- Treatment: pyrimethamine + sulfadiazine + folinic acid (to prevent marrow suppression) for at least 6 weeks; clindamycin replaces sulfadiazine in sulphonamide allergy.
- Improvement within about 2 weeks supports the diagnosis; if no response, think of primary CNS lymphoma (often a single lesion; linked with EBV).
Multiple ring-enhancing lesions in an AIDS patient suggest toxoplasmosis; a single lesion that does not respond to anti-toxoplasma treatment suggests primary CNS lymphoma.
Cryptococcal meningitis
- Cryptococcus neoformans (yeast in pigeon droppings), inhaled.
- Subacute headache, fever, nausea, confusion; neck stiffness often absent.
- Raised intracranial pressure is common and dangerous.
- CSF: high opening pressure, India ink shows capsulated yeasts, cryptococcal antigen (CrAg) positive; culture positive.
- Treatment: induction with amphotericin B + flucytosine (2 weeks), then fluconazole consolidation and maintenance; repeated lumbar punctures to lower pressure. Steroids are avoided.
Cytomegalovirus (CMV)
- CD4 below 50.
- Retinitis: floaters, blurred vision, field loss; fundus shows haemorrhages and white exudates along vessels ("pizza pie" or "cottage cheese and ketchup").
- Also colitis, oesophageal ulcers, encephalitis, adrenalitis.
- Treatment: ganciclovir IV or valganciclovir orally; foscarnet or cidofovir as alternatives.
Tuberculosis in HIV
- The commonest opportunistic infection and leading cause of death in people with HIV in South Asia and Africa.
- Occurs at any CD4 count; at low counts it is often extrapulmonary or disseminated, smear-negative, with atypical CXR (lower zone, no cavities).
- Use GeneXpert (Xpert MTB/RIF) and urine LAM testing where available.
- Rifampicin interacts with many ARVs (dolutegravir dose is doubled).
Others to recognise
| Condition | Clue |
|---|---|
| Oral candidiasis | White plaques that scrape off; fluconazole |
| Oesophageal candidiasis | Painful swallowing (odynophagia); an AIDS-defining illness |
| Oral hairy leukoplakia | White ridged plaques on the side of the tongue that do not scrape off; EBV |
| Kaposi sarcoma | Purple skin, mouth, gut or lung lesions; HHV-8 |
| PML | Progressive focal deficits, non-enhancing white-matter lesions; JC virus |
| Cryptosporidiosis | Chronic watery diarrhoea; modified acid-fast oocysts in stool |
| MAC | Fever, weight loss, anaemia, diarrhoea, hepatosplenomegaly; clarithromycin + ethambutol |
| HIV-associated nephropathy | Nephrotic syndrome; collapsing FSGS |
Antiretroviral therapy (ART)
When to start
- Everyone with HIV, whatever the CD4 count, as soon as they are ready (same day if possible).
- With most opportunistic infections, start ART within 2 weeks of starting OI treatment.
- Exceptions (delay to reduce IRIS and death):
- Cryptococcal meningitis: delay ART about 4–6 weeks after antifungal treatment starts.
- TB meningitis: delay ART to after the intensive phase begins (several weeks). In other TB, start ART within the first weeks of TB treatment, sooner if CD4 is very low.
What to start
- Three drugs: two NRTIs + one drug from another class.
- WHO preferred first-line: tenofovir + lamivudine (or emtricitabine) + dolutegravir ("TLD").
| Drug class | Examples | Key adverse effects |
|---|---|---|
| NRTIs | Tenofovir, lamivudine, emtricitabine, abacavir, zidovudine | Tenofovir: kidney damage, bone loss; abacavir: hypersensitivity (HLA-B*5701); zidovudine: anaemia |
| NNRTIs | Efavirenz, nevirapine, rilpivirine | Efavirenz: vivid dreams, CNS effects; nevirapine: rash, hepatotoxicity |
| Integrase inhibitors | Dolutegravir, raltegravir | Weight gain, insomnia; high barrier to resistance |
| Protease inhibitors | Lopinavir/ritonavir, atazanavir, darunavir | GI upset, lipid changes; atazanavir causes jaundice (unconjugated) |
- Monitoring: viral load at about 6 months then yearly; aim for undetectable (below 50 copies/ml). Two consecutive raised viral loads mean treatment failure; check adherence first, then resistance.
Immune reconstitution inflammatory syndrome (IRIS)
- Paradoxical worsening of a known infection (TB, cryptococcus, CMV) or unmasking of a hidden one, usually within weeks of starting ART, as immunity recovers.
- Risk is highest with a very low CD4 count and when ART starts very soon after OI treatment.
- Management: continue ART in most cases, treat the infection, steroids for moderate or severe TB-IRIS.
A patient with HIV-TB who worsens 3 weeks after starting ART, with new fever and bigger lymph nodes, usually has IRIS, not drug-resistant TB. Check adherence and resistance, but do not stop ART automatically.
Prophylaxis
| Prophylaxis | Indication | Drug |
|---|---|---|
| PCP (and toxoplasma) | CD4 below 200 (WHO in resource-limited settings uses higher thresholds) | Co-trimoxazole (dapsone if allergic) |
| TB preventive therapy | All people with HIV once active TB is excluded | Isoniazid (with pyridoxine) or rifapentine-based regimens |
| Cryptococcal | Positive serum CrAg with no meningitis | Fluconazole |
- Stop primary prophylaxis when the CD4 count stays above 200 on ART.
- Live vaccines (MMR, varicella) should not be given when CD4 is below 200.
Prevention
- Post-exposure prophylaxis (PEP): three-drug ART started as soon as possible and within 72 hours, continued for 28 days. Test the exposed person at baseline and follow-up. After a needle-stick from an HIV-positive source, the risk is about 0.3% without PEP.
- Pre-exposure prophylaxis (PrEP): tenofovir-based for people at high ongoing risk.
- Prevention of mother-to-child transmission: ART for all pregnant women, infant prophylaxis, safe delivery and feeding advice.
- Safe injection practice, screened blood, condoms, needle exchange.
"200 – PCP, 100 – Toxo, 50 – CMV and MAC": count down as the CD4 falls.
Expect: retrovirus biology (reverse transcriptase, CD4 with CCR5/CXCR4); seroconversion illness and the window period; 4th-generation (antibody + p24) testing; PCR for infants; CD4 thresholds for each opportunistic infection; PCP features and treatment with co-trimoxazole and steroids; ring-enhancing lesions (toxoplasma versus lymphoma); cryptococcal meningitis with India ink and CrAg; CMV retinitis; TB as the commonest OI; ART for all and TLD as first line; abacavir and HLA-B*5701; IRIS and ART timing; co-trimoxazole prophylaxis; PEP within 72 hours for 28 days.
Quick revision
- Retrovirus; gp120 binds CD4 + CCR5/CXCR4.
- Screen with antibody + p24 (4th generation); infants need PCR.
- CD4 = immune status; viral load = treatment response.
- Below 200: PCP; below 100: toxoplasma, cryptosporidium; below 50: CMV, MAC.
- PCP: co-trimoxazole 21 days + steroids if hypoxic.
- Toxo: pyrimethamine + sulfadiazine + folinic acid.
- Cryptococcus: amphotericin + flucytosine, then fluconazole; delay ART 4–6 weeks.
- ART for all: TLD; IRIS = paradoxical worsening; PEP within 72 h for 28 days.
Written by The House Job from standard references (Kumar and Clark's Clinical Medicine; Levinson's Review of Medical Microbiology and Immunology).
FAQ
What does a 4th-generation HIV test detect?
Antibodies to HIV-1 and HIV-2 and the p24 antigen together, so it shortens the window period compared with antibody-only tests.
At what CD4 count does Pneumocystis pneumonia usually occur?
Usually below 200 cells/mm3, which is also the level at which co-trimoxazole prophylaxis is started.
Why is ART delayed in cryptococcal meningitis?
Starting ART too early raises the risk of severe immune reconstitution inflammation in the brain and increases deaths; a delay of about 4–6 weeks is advised.
How soon must PEP be started after a needle-stick injury?
As soon as possible, ideally within hours and no later than 72 hours, and it is continued for 28 days.