Treatment of HIV/AIDS

There is, at present, no cure for HIV infection.

The core component of treatment and care of patients living with HIV is provision of antiretroviral therapy (ART) (1). Seek specialist advice regarding antiviral therapy.

• ART is recommended for all individuals with HIV regardless of CD4 count (2)
• aims of ART are
  • clinical – prolongation of life and improvement of its quality
  • immunological – restore and preserve immunological functions to prevent opportunistic infections
  • virological – reduction of the viral load to prevent progression of the disease in untreated individuals and to prevent and delay the development of drug resistance
  • epidemiological – reduction and prevention of onward HIV transmission (1)

ART can be divided into six classes based on their molecular mechanisms and resistance profiles:

• nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)
• non–nucleoside reverse transcriptase inhibitors (NNRTIs)
• integrase inhibitors
• protease inhibitors (PIs)
• fusion inhibitors
• coreceptor antagonists (3)

In addition, two drugs, ritonavir (an old HIV drug given at subtherapeutic doses) and cobicistat are used as pharmacokinetic enhancers (or boosters) to enhance the blood levels (2).

Mutation of the HIV during replication has led to rapid development of resistance to most single anti-HIV drugs. Due to this reason anti-HIV drugs are used in combinations of three or more.

• the choice of initial triple therapy is with two nucleoside reverse transcriptase inhibitors (NRTIs) plus either a ritonavir-boosted protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitors (NNRTIs), or integrase inhibitor (INI) (4). There are also regimens based on two NRTIs plus two PIs with the primary reason for combining PIs being to improve pharmacokinetics

The decision to initiate ART should be based on two different CD4 counts, ideally at least 7 days apart because of variability in the CD4 count itself and to rule out laboratory mistakes and other variances (for example, concurrent illnesses).

• in case of concurrent illnesses, repeat of CD4 count should be done only after the illness is cured. however treatment should not be delayed if the patient is unwell or if the second count cannot readily be performed (1)

WHO recommendations for initiating ART for patients with HIV:

All patients should be regularly monitored for treatment success of ART:

During early weeks of treatment, the speed of the viral load reduction should be monitored and if the speed of reduction is insufficient treatment failure due to adherence problems, inadequate drug levels or pre-existing primary drug resistance should be taken in to account (5).

Drug resistance to ART may arise due to: non-adherence to medication or drug-drug interactions and, once established, is irreversible. Cross-resistance between classes of drugs means treatment choices are further limited.

There is little data available on which to base the decision on whether to start treatment in primary (acute) HIV infection. UK guidelines recommend that all individuals with suspected or diagnosed PHI are reviewed promptly by an HIV specialist and offered immediate ART (4)

During the later stages of HIV infection management is based heavily the treatment of HIV-related infections or illnesses as they occur. On occasion, tissue biopsy may be necessary and this may often throws up surprises, reflecting the multiple pathology of the condition.

CD4 cell count-guided antiretroviral treatment interruption strategy

• in patients with HIV, CD4+ cell count-guided antiretroviral therapy interruption increase the risk of opportunistic disease and death more than continuous therapy (6) - a review concluded that "...analysis by Lundgren et al showed that increased risk of opportunistic disease or death was related to duration of uncontrolled HIV replication, even at relatively high CD4+ levels. This suggests that today’s simpler, less expensive, and less toxic treatments might be started earlier and should rarely, if ever, be intentionally interrupted..." (6)

Reference:

• (1) World Health Organization (WHO) 2007. HIV/AIDS treatment and care. Clinical protocols for the WHO European region
• (2) Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. National Institutes of Health, U.S. Department of Health and Human Services, aidsinfo.nih.gov
• (3) Arts EJ, Hazuda DJ. HIV-1 Antiretroviral Drug Therapy. Cold Spring Harbor Perspectives in Medicine. 2012;2(4):a007161.
• (4) Churchill D et al. British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2015. HIV Med. 2016;17 Suppl 4:s2-s104.
• (5) British HIV Association 2008. British HIV Association guidelines for the treatment of HIV-1-infected adults with antiretroviral therapy 2008
• (6) Prescriber (2001), 12 (18), 18-27.