Describe the antiviral drugs and the principles of antiretroviral therapy.

General Principles

• Viruses use host cellular machinery, so there are few unique targets — which is why antivirals are fewer, narrower and more toxic than antibacterials
• Most are effective only during active replication, and none eradicates latent virus
• Targets exploited — viral attachment and entry, uncoating, nucleic acid synthesis (the commonest), protein processing, and release

Antiherpes and Antiviral Agents

Antiretroviral Therapy

• India’s national programme now uses TLD — tenofovir + lamivudine + dolutegravir as a single daily fixed-dose tablet, which is effective, well tolerated, cheap and simple
• Always at least three drugs from at least two classes; monotherapy invariably selects resistance
• Treat everyone, regardless of CD4 count — early treatment improves survival and, by suppressing viral load, prevents transmission ("undetectable = untransmittable")
• Immune reconstitution inflammatory syndrome — paradoxical worsening as immunity recovers, most often unmasking tuberculosis; it is not treatment failure and antiretrovirals are continued
• Rifampicin markedly reduces antiretroviral levels by enzyme induction; the dolutegravir dose is doubled during tuberculosis treatment

Hepatitis Antivirals

• Hepatitis B — tenofovir and entecavir are first-line; they suppress but do not eradicate the virus, so treatment is usually long-term. Lamivudine alone selects resistance rapidly and is no longer used as monotherapy
• Hepatitis C — direct-acting antivirals (sofosbuvir, daclatasvir, velpatasvir, ledipasvir) achieve cure in over 95% with 12 weeks of oral treatment and few side effects — one of the most striking therapeutic advances of recent decades. Generic production in India has made them affordable across much of the world
• Screen for hepatitis B before immunosuppression or chemotherapy, since reactivation can be fulminant

Monitoring and Failure of Antiretroviral Therapy

• Viral load is the key monitoring test — measured at 6 months, 12 months and then annually; the target is an undetectable level
• CD4 count indicates immune recovery and the need for opportunistic infection prophylaxis, but is no longer used to decide when to start treatment
• Treatment failure is defined virologically — a viral load above 1,000 copies/mL on two occasions despite adherence support
• Before changing a regimen, confirm adherence; most apparent failure is non-adherence, and switching without addressing it merely burns through the remaining options
• Resistance testing guides the second-line regimen where available
• India’s national programme provides free antiretrovirals through ART centres, with second-line and third-line regimens available; the limiting factors are testing capacity, retention in care and stigma rather than drug supply

Applied Aspects

• Start aciclovir early in herpes zoster, ideally within 72 hours of the rash, to reduce acute pain and the risk of post-herpetic neuralgia
• Hydrate patients receiving intravenous aciclovir and infuse slowly to prevent crystalline nephropathy
• Post-exposure prophylaxis for HIV must begin within hours — ideally under 2 hours and certainly within 72 — and continue for 28 days
• Adherence above about 95% is required for durable viral suppression; below that, resistance emerges. Fixed-dose single-tablet regimens exist precisely to make this achievable
• Never stop antiretrovirals abruptly in a patient admitted for another reason; interruption causes viral rebound and resistance, and drugs must be continued or a plan made
• Prevention of mother-to-child transmission with antiretrovirals reduces transmission from about 30% to under 2%, and is one of the most cost-effective interventions available
• Pre-exposure prophylaxis with tenofovir-emtricitabine is highly effective for those at substantial ongoing risk, and requires regular HIV testing and renal monitoring
• Test for HLA-B*57:01 before abacavir; the hypersensitivity reaction is severe and rechallenge can be fatal
• Treat hepatitis C in everyone infected — the direct-acting antivirals cure over 95% in 12 weeks, and Indian generics have made this affordable, which is among the most consequential therapeutic changes of the past decade
• Oseltamivir must be started within 48 hours to be worthwhile in influenza; given later it has little effect, and this is the commonest reason it appears ineffective
• Antivirals do not eradicate latent virus — herpes and HIV persist regardless of treatment, and patients must understand that suppression is not cure
• Check renal function before and during tenofovir, and consider the alafenamide form where bone or renal disease is a concern
• Ask about traditional and herbal medicines in patients on antiretrovirals; St John wort in particular induces enzymes and causes treatment failure
• Disclosure and stigma determine adherence more than any pharmacological factor, and support at the ART centre is part of the treatment rather than an addition to it
• Hepatitis B and HIV share drugs — tenofovir and lamivudine treat both — so a patient with both must never be given an HIV regimen that leaves the hepatitis B inadequately covered, and stopping treatment can cause a hepatitis flare
• Vaccinate against hepatitis A and B in HIV, and give pneumococcal and influenza vaccines; live vaccines are avoided at very low CD4 counts
• Screen every HIV patient for tuberculosis at every visit, since it remains the commonest opportunistic infection and the leading cause of death in India
• Antiretroviral therapy is lifelong, and the counselling given at the start largely determines whether the patient is still virally suppressed a decade later
• Dolutegravir absorption is reduced by antacids, calcium and iron, which patients often take without mentioning; doses must be separated