* Further Reading: Laboratory Requirements for the Safe and Effective Use of Antiretrovirals. Guidance Module number 5. Guidance Modules on Antiretroviral Treatments. WHO/UNAIDS. WHO/ASD/98.1; UNAIDS/98.7

Patient on ART should be closely followed to assess adherence to therapy as well as tolerance of the treatment and efficacy of the treatment. At the start of treatment it is advisable for patients to be seen monthly and once stabilised they can then be seen every three to four months. More frequent visits may certainly be dictated by various intercurrent needs so follow up plans should be tailored to individual patient requirements.

3.5.1. Monitoring adherence to ART

PLHA from resource poor countries have identified the following as important determinants of adherence to ART:

• the quality of initial and continuing counselling resulting in well-informed decisions and commitment by the patient to start and to maintain ART.

• the availability of accessible, knowledgeable and committed medical support teams.

• the assurance of a continued supply of antiretroviral medications

At each follow up visit, adherence to the treatment should be discussed in depth.

The “drug timetable” which was made at the onset of ART should be revisited to see how this is functioning in real life and the patient should be assisted to work through any difficulties they have encountered. Close co-operation and communication between clinicians, pharmacists/dispensers, other counsellors, patients and family are vital. Carers need to remain aware of the issues surrounding individual patients’ access to ART in order to anticipate difficulties in adherence and to plan support.

3.5.2. Monitoring tolerance to ART

The causes of any new symptoms or signs developing after the initiation of ART should be identified whenever possible. New symptoms may be related to intercurrent illness or due to adverse effects of antiretroviral drugs. Shortly after commencing ART, certain opportunistic infections may become clinically apparent as a result of the syndrome of immune reactivation, and these should be diagnosed and treated.

If new complaints are due to adverse effects of drugs, these should be explained to the patient and appropriate measures implemented, be this by adapting the drug regimen, providing symptomatic treatment or giving simple reassurance.

Direct questioning on early symptoms of the documented clinically serious adverse effects of antiretroviral drugs is mandatory, as is systematic physical and laboratory examination to look for indicative signs. In this way adverse effects like severe anaemia and neutropenia; polyneuritis; pancreatitis; hepatitis; nephrolithiasis and serious hypersensitivity dermatitis can be detected early and remedial actions taken.

Table 6 lists the ancillary laboratory tests that should complement patient interview and physical examination to monitor for drug toxicity. The necessity for these tests will vary according to the antiretroviral drugs being used and to whether or not tests are indicated by the patient’s symptoms.

3.5.3. Monitoring the efficacy of ART

The efficacy of ART is indicated by clinical improvement of the patient and by a favourable response of the biological markers of HIV infection, namely CD4+ cell counts and plasma “viral load”.

Some clinical indicators of disease progression and response to treatment:

• a gain in body weight
• increase in total lymphocyte count
• decrease in frequency/severity of opportunistic infections
• decrease in occurrence/severity of HIV related malignancies

CD4 lymphocyte counts*

* Further Reading: Laboratory Requirements for the Safe and Effective Use of Antiretrovirals. Guidance Module number 5. Guidance Modules on Antiretroviral Treatments. WHO/UNAIDS. WHO/ASD/98.1; UNAIDS/98.7

The clinical manifestations of HIV infection are mostly dependent on the levels of CD4+ cells; the CD4 count. Where viral load assays are not available, a rise in the CD4 count is an acceptable indication of treatment efficacy. In addition, CD4+ cell levels are very useful when deciding on the time to start or to stop prophylaxis against certain opportunistic infections. In patients in whom undetectable viral load levels have been achieved, which indicates the desired suppression of retroviral activity, a median increase in CD4+ cells of about 100-200 cells per year may be expected. The magnitude of this increase in CD4+ cells will depend on the baseline CD4 count as well as other factors which influence the outcome of ART. It is worth noting that following initiation of therapy, the “CD4 response” as evidenced by rising CD4+ cell counts, is much slower than the “viral load response” and may take several months to years to be complete. A reasonable frequency of CD4 count measurements in patients on ART is every 3-6 months.

Plasma HIV-1 RNA assay or “viral load”*

* Further Reading: Laboratory Requirements for the Safe and Effective Use of Antiretrovirals. Guidance Module number 5. Guidance Modules on Antiretroviral Treatments. WHO/UNAIDS. WHO/ASD/98.1; UNAIDS/98.7

The plasma viral load is a measure of HIV replication and the suppression of viral replication is one of the primary goals of antiretroviral therapy. Sustained suppression of HIV replication is not only an indication of the efficacy of treatment but also may delay or prevent the emergence of drug resistance. It is advisable to measure viral load shortly after initiating ART i.e. within 1 to 3 months, as a check on the effectiveness of the therapy. It also becomes necessary to measure the viral load when the response to therapy, as shown by the other indicators, is unfavourable and whenever a change in the therapeutic regimen is contemplated.

When interpreting the results of viral load assays caution is advised for several reasons:

• viral load levels vary according to the technique that has been used, the laboratory where the test has been done, the time and the way the sample was transferred to the laboratory.

• viral load levels may be increased after a recent infection, vaccination or lapse in treatment;

• certain viral strains that are particularly frequent in developing countries may be difficult to detect with some of the commercially available testing methods.

Wherever ART is introduced, a reliable reference laboratory, where the necessary biological monitoring tests can be assured, should be established.