HIV Pharmacology

In 2020, 37.7 million people globally were living with HIV. With access to anti-retroviral therapy (ART) having dramatically expanded in the last decade, 28.2 million individuals were accessing treatment as of June 2021. Of the 20.7 million people living with HIV/AIDS (PLWHA) in Eastern and Southern Africa, approximately 15 million are on treatment (UNAIDS, 2021).

The increased access to ART has led to substantial improvement in the life expectancy of patients infected with HIV, which is now treated as a chronic disease requiring life-long ARV treatment. HIV is a rolling science and the disease landscape is constantly changing. South Africa remains one of the countries with the highest burden of HIV, with 13.7% of the total population being HIV positive (STATS SA 2021). Access to ART has increased significantly over the last 20 years in the country through multiple landmark events:

  • 2004: ART programme officially begins through the Operational Plan for Comprehensive HIV and AIDS Care, Management and Treatment for South Africa. Accredited service points in all districts provide ARVs, covering only 5% of the country’s public healthcare facilities
  • 2006: National Strategic Plan for HIV & AIDS and STIs (2007-2011) implemented, increasing government provision of ARVs
  • 2009: Launch of National HIV Counselling and Testing campaign, with all public health facilities prepared to provide ARVs
  • 2010: National Department of Health revises ART guidelines to expand and include treatment to all children under 1 year, all pregnant women regardless of CD4+ count and all TB-HIV co-infected patients with a CD4+ count of <350 cells/μl, and changing ART for both first- and second-line therapy to make it safer
  • 2011: National Strategic Plan for HIV & AIDS (2012-2016) launched, with strong focus on key populations
  • 2012: National ART guidelines updated to increase the initiation threshold of ART to 350 cells/μl for all adults, as well as to expand access thresholds for children, introducing fixed-dose combinations
  • 2015: ART initiation threshold updated to CD4<500 cells/μl
  • 2016: Introduction of universal ‘Test and Treat’.
  • 2017: National guidelines shift towards same-day test and treat.
  • 2019: INSTI Dolutegravir replaces Efavirenz in first line and use in second line ART

There are multiple classes of ART used to maintain the health of an HIV infected individual (see table­ below). Different modes of action allow more than one ARV to be used in combination with other ARVs. Although HIV infection cannot be cured, the combination of ARV drugs allows for the successful control of the infection for many years. The life cycle of HIV, which these drugs interfere with, is discussed more in a later section.

Classes of HIV antiretrovirals and their mechanisms of action.
Nucleoside Reverse Transcriptase Inhibitors (NsRTIs)Act as nucleotide base analogues and block DNA chain elongation.
Nucleotide Reverse Transcriptase Inhibitors (NtRTIs)Act as nucleotide base analogues and block DNA chain elongation.
Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)Bind irreversibly to HIV’s reverse transcriptase enzyme, which impairs enzyme functioning.
Protease inhibitors (PIs)Inhibit HIV’s protease enzyme, preventing production of infectious viral particles. Inhibition of this process results in immature, non-infectious virions.
Entry inhibitors (EIs)Block HIV from entering a host CD4 cell.
Integrase Srand Transfer Inhibitors (INSTIs) (‘integrase inhibitors’)Prevent the transfer of viral DNA strands into the host chromosomal DNA.

The goals of ART are to:

  • Maximally and durably suppress plasma HIV RNA
  • Preserve and restore immunologic function
  • Reduce HIV-associated morbidity
  • Prolong the duration and quality of survival
  • Prevent HIV transmission.

Triple therapy has traditionally always been the standard of care (Table 3.1b). The development of early ARVs, classified as ‘first generation’, lead the way for development of more effective ‘second generation’ ARVs (Table X). A clinical interchangeability is known to exist between 3TC and FTC, sometimes denoted as XTC. Either of these two drugs can be as part of therapy. Available data current supports the clinical and programmatic interchangeability of 3TC and FTC. Protease inhibitors (PIs) administered in South African ART regimens are given with low-dose Ritonavir (/r) for pharmacokinetic boosting, which allows for a lower PI dose, prolongs the accompanying PI drug circulation, and decreases chances of developing drug resistance. Boosting also minimises drug side effects, as lower dose of active drug can be used with same outcome.