Antiviral treatment for primary VZV infection is indicated in neonates, children and adults with HIV infection or other immunodefiencies, as well  those with severe disease. These include oral valaciclovir, famiciclovir or aciclovir (dosages and durations provided in Table 3). Treatment should begin within 24–48 hours of onset, however in immunocompromised patients (including people living with HIV) antivirals are indicated regardless of rash duration.  

Aciclovir, valaciclovir and famciclovir are efficacious in acute HZ, and should be used in ophthalmic HZ and can ameliorate postherpetic neuralgia. In immunocompromised populations such as PLWHIV, oral antivirals should be commenced even if onset is greater than 72 hours. (21) All three drugs are effective and with a similar safety profile, however valaciclovir and famiciclovir may be associated with reduced risk of post-herpetic neuralgia. (36) 

Management of systemic VZV infection or disseminated HZ requires intravenous aciclovir and should be guided by Infectious Diseases specialists with appropriate subspecialty advice, for example Neurology for encephalitis or Ophthalmology for keratitis. (37) Aciclovir-resistant varicella zoster infection is rare, especially in the post ART era, but when it does occur it is associated with significant mortality and morbidity. These patients usually have advanced disease with CD4 cell counts below 20 cells/μL. The presence of atypical lesions or a failed clinical response should prompt evaluation for acilovir susceptibility. Foscarnet is recommended for the treatment of acilovir-resistant zoster infection (38).  

The live-attenuated varicella   vaccine   has   been   demonstrated   to   be   safe   and immunogenic   in   both adults and children living   with   HIV, with no reported case of vaccine-associated infection. (39-41) Australian guidelines recommend children over 12 months with HIV and age-specific CD4+ count of >15% total lymphocytes; as well as adults with HIV who are seronegative for varicella and with a CD4+ count >200 cells/μL receive  two doses of the monovalent varicella vaccine at least three months apart. (42) Combination vaccines, such as the measles-mumps-rubella-varicella vaccine, have not been evaluated for safety in immunocompromised peoples and are therefore not recommended.  

In such immunocompromised patients, recombinant vaccines against HZ are preferred over live-attenuated variants due to risk of disseminated vaccine strain VZV infection associated with the latter.  Recombinant vaccination against HZ is recommended by Australian guidelines and funded for immunocompromised adults over 18 years old, including ‘untreated or advanced HIV’, or any adult over 50 years old.  (42) However, in adults living with HIV who have CD4+ counts greater than 200 cells/μL, live-attenuated vaccination has not been associated with vaccine-related infection, and may be considered if recombinant vaccines are not accessible. As of 2024, The varicella zoster virus recombinant vaccine (RZV) is now recommended for adults with HIV and CD4+ count < 200 cells/ μL in the National Immunisation Program (43). 

Zoster immunoglobulin is indicated for patients with HIV infection within 96 hours to 10 days of significant first VZV exposure (e.g. household or classroom contact) and who do not have immunity against varicella (44). Protection from HZV immunoglobulins may last for approximately 3 weeks, or alternatively  aciclovir can be given up to 7 days post exposure (45). Recurrent HZV despite vaccination and adequate suppression of HIV viral load may benefit from VZV suppression using oral aciclovir, (46) however this is not an approved indication for aciclovir in Australia.