GENERAL PRINCIPLES OF ANTIRETROVIRAL TREATMENT

Initial evaluation checklist for patients starting ART

Before initiating ART, a full evaluation of the patient must be done. This includes:

  • Assessment of the history, physical exam and baseline laboratory tests to assess disease progression and any other conditions
  • Staging the patient’s stage using WHO clinical staging
  • Counselling and assessing patient’s readiness to start ART

Assessment of patient’s history

  • Level of understanding of HIV/AIDS
  • Length of time since the diagnosis of HIV infection
  • Demographics and lifestyle: whether employed and nature of work
  • History of previous ART, prior use of nevirapine during pregnancy
  • Pregnancy risks: contraception options and choices, current or planned pregnancy, access to contraceptive services
  • Sexual risks and disclosure: willingness to practice safer sex, disclosure of HIV serostatus, use of condoms, HIV counselling, and testing of sex partners and children
  • Symptoms of chronic pain and depression
  • History of opportunistic infections and other significant illnesses e.g. TB and STIs, hospitalisations, and surgeries
  • Current medications (including anti-TB drugs, traditional therapies, etc.)

Physical exam

  • Weight
  • Nutritional status
  • Functional capacity and level of disability
  • Vital signs, skin, eyes, oropharynx (presence of thrush), lymph nodes, lungs, heart, abdomen, genital tract (STIs), extremities, nervous system

Baseline laboratory tests to assess immunosuppression and
disease aggressiveness

  • Confirming HIV serostatus
  • CD4 testing
  • Pregnancy test
  • Full blood count particularly for patients starting on a AZT-containing regimen

Baseline Labs to assess general health and diagnose any
pre-existing HIV complications

  • Sputum smear for AFB for patients who have coughed for > 2-3 weeks and a chest X-ray for patients who have unproductive cough or whose AFB smears are negative
  • Urine analysis for proteinuria, particularly for patients starting on TDF-containing regimen
  • Syphilis screening
  • Hepatitis B screening
  • Liver and renal function tests if available
  • Cryptococcal antigen screening for patients whose CD4 count is < 100 cells/ml
  • Symptom-directed lab tests to diagnose pre-existing illnesses

Staging of disease

  • Using WHO clinical criteria.

Counselling and assessment of patient’s readiness to start therapy

  • Assess for education, information or counselling support needs
  • Develop an adherence plan

Background of ART

A cure for HIV is not yet available, but by using highly active antiretroviral therapy (HAART), it is possible to promote growth in children and prolong the survival of
all HIV infected patients, reduce their morbidity, and improve their quality of life.

Highly active antiretroviral therapy (HAART) is defined as therapy which is potent enough to suppress HIV viraemia to undetectable levels (< 50 copies/mL), and is
durable in its virologic effect.

  • HAART conventionally includes three or more medicines from at least two classes to achieve full and durable suppression of viral load
  • Known sub-optimal regimens, e.g. monotherapy, double nucleoside, or certain triple nucleoside combinations are not HAART and are contraindicated in HIV disease

Goals of treatment with antiretroviral medicines are to:

  • Inhibit viral replication as reflected in plasma HIV concentration to as low as possible and for as long as possible. This promotes restoration of the immune
    system.
  • Preserve or enhance the immune function (CD4 restoration), which prevents/delays the clinical progression of HIV disease
  • Minimise toxicities and side effects associated with the medicines
  • Improve quality of life and reduce HIV-related morbidity and mortality
  • Promote growth and neurological development in children
Tools to achieve the goals of therapy
  • Maximisation of adherence to ART: adequate support to patient to adhere to treatment and/or access to community/facility level adherence counselling
    • Disclosure of HIV serostatus reinforces patient’s adherence to ART
  • Rational sequencing of medicines to preserve future treatment options
  • Use of ARV medicine resistance testing when appropriate and available
  • Use of viral load estimates for monitoring

Principles of ART

Antiretroviral therapy is part of comprehensive HIV care.

The guiding principles of good ART include:

  • Efficacy and durability of the chosen medicine regimens
  • Freedom from serious adverse effects; low toxicity
  • Ease of administration including no food restrictions, better palatability, and lower pill burden
  • Affordability and availability of medicines and medicine combinations
  • Organised sequencing – spares other available formulations for use in second line while allowing for harmonization of regimens across age and population
  • Ongoing support of the patient to maintain adherence

Limitations of ART

  • Antiretroviral medicines are not a cure for HIV but greatly
    improve quality of life when used appropriately
  • ARVs are relatively expensive, require an adequate
    infrastructure, and knowledgeable healthcare workers
  • Medicine interactions and resistance may decrease the
    potency of ARVs
  • Patients may develop adverse medicine reactions
  • Patients have to take at least 95% of their pills in order to
    respond well (adherence is key to successful therapy)
  • The medications have to be taken for life
  • Some patients may not respond (benefit) to treatment and
    continue to regress in spite of high adherence
  • Children are dependent on adults for adherence to ART

Available agents for ART

At present, antiretroviral medicines come in six classes, which attack different sites and stages of the HIV life cycle, thereby interfering with its reproduction.

CLASS EXAMPLES
Nucleoside reverse transcriptase
inhibitors (NtRTIs)
incorporate
themselves into the DNA of the
virus, thereby stopping the building
process
  • Tenofovir (TDF)
  • Zidovudine (AZT)
  • Lamivudine (3TC)
  • Abacavir (ABC)
Non-nucleoside reverse
transcriptase inhibitors
(NNRTIs)
stop HIV production by
binding directly onto the reverse
transcriptase enzyme, and prevent
the conversion of RNA to DNA
  • Efavirenz (EFV)
  • Nevirapine (NVP)
  • Etravirine (ETV)
Integrase inhibitors interfere with
the HIV DNA’s ability to insert itself
into the host DNA and copy itself.
  • Dolutegravir
    (DTG)
  • Raltegravir (RAL)
Protease inhibitors (PIs) prevent
HIV from being successfully
assembled and released from the
infected CD4 cell. Boosted PIs
are combinations of low-dose
ritonavir (RTV) with a PI for
pharmacoenhancement
  • Atazanavir (ATV)
  • Lopinavir (LPV)
  • Darunavir (DRV)
  • Ritonavir (RTV,
    abbreviated as ”r” if
    boosting other PIs,
    e.g. ATV/r, LPV/r
Entry inhibitors (HIV fusion
inhibitors)
prevent the HIV virus
particle from infecting the CD4 cell
  • Enfuvirtide
    (T-20)
CCR5 antagonists block the CCR5
co-receptor molecules that HIV uses
to infect new target T-cells. Some
forms of HIV use a different coreceptor
and thus, some patients may
not benefit from maraviroc
  • Maraviroc

Initiation of ART

It is recommended to initiate ART at the earliest opportunity in all documented HIV-infected adults, adolescents and children regardless of CD4 count and WHO clinical staging (Test and Treat)

Evidence and programmatic experience have shown that early initiation of ART results in reduced mortality, morbidity and HIV transmission outcomes. However,
priority should be given to patients with lower CD4 counts as well as those who are symptomatic

A CD4 count is not necessary for initiation but it can be useful to assess risk of opportunistic infections.

ART in children

The vast majority (about 90%) of infants and children with HIV acquire the infection through mother-to-child transmission.

HIV infection follows a more aggressive course among infants and children than among adults; 30% die by age 1 year and 50% die by age 2 years without access to life-saving medicines, including ART and preventive interventions, such as cotrimoxazole prophylaxis.

Early HIV diagnosis and ARV treatment is critical for infants. A significant number of lives can be saved by initiating ART for HIV-positive infants immediately after
diagnosis within the first 12 weeks of life.

General principles

  • ARV doses need to be adjusted from time to time as the children grow quickly and thus, their weight changes.
  • Before a child begins ART, the following assessments must be made:
    • Readiness of parents/caretakers or child (if older) to start ART
    • Complete pre-treatment baseline assessment (see previous sections)