20.1. Guiding principles

1. Laboratory monitoring is not a prerequisite for the initiation of ART.
2. CD4 and viral load testing are not essential for monitoring patients on ART.
3. Symptom-directed laboratory monitoring for safety and toxicity is recommended for those on ART.
4. If resources permit, use viral load in a targeted approach to confirm suspected treatment failure based on immunological and/or clinical criteria.
5. If resources permit, use viral load in a routine approach, measured every 6 months, with the objective of detecting failure earlier than would be the case if immunological and/or clinical criteria were used to define failure.

20.2. Laboratory monitoring on ART

Two RCTs (DART and HBAC) and two observational studies have assessed laboratory monitoring strategies. The DART study compared a laboratory-driven monitoring strategy (CD4 cell count every 3 months) to a clinically-driven monitoring strategy.(211) There was a small but statistically significant difference in mortality and disease progression in favour of the laboratory strategy but only from the third year on ART. HBAC compared clinical monitoring alone to clinical monitoring and the addition of CD4 cell count or CD4 cell count and viral load, both performed every 3 months. In this study, clinical monitoring alone was associated with an increased rate of AIDS-defining events and a trend towards increased mortality. No additional benefit was seen from adding quarterly viral load measurements to CD4 cell count in the first 3 years of ART.(148)

The two observational studies which compared immunological and clinical versus virological, immunological and clinical monitoring reported that, in programmes with virological, immunological and clinical monitoring a switch to second-line therapy occurred earlier, more frequently and at higher CD4 counts.(212) Three further monitoring trials, all of which are assessing viral load monitoring in different strategies, are progressing in Cameroon, Thailand, and Zambia.(213–215)

For NNRTI-containing regimens, symptom-directed laboratory monitoring of liver enzymes is recommended. Symptom-directed monitoring means ordering tests only when the care provider recognizes signs and symptoms of potential ART-related toxicity. For women initiating NVP with a CD4 count of 250–350 cells/mm³, if feasible, it is recommended (but not required) to monitor hepatic enzymes at weeks 2, 4 and 12 after initiation.

For AZT-containing regimens, haemoglobin (Hb) measurement is recommended before the initiation of AZT and then as indicated by signs/symptoms. Patients receiving AZT-containing regimens and with low body weight and/or low CD4 cell counts are at greater risk of anaemia. These patients should have routine Hb monitoring 1 month after initiating AZT and then at least every 3 months. AZT should not be given if Hb is <7 g/dl.

For TDF-containing regimens, creatinine clearance calculation is recommended, if feasible, before initiation and every 6 months. The inability to perform creatinine clearance is not a barrier to TDF use. Creatinine clearance monitoring is recommended in those with underlying renal disease, of older age groups, and with low body weight or other renal risk factors such as diabetes or hypertension.

There is evidence that individuals taking TDF and a PI/r may experience greater median decline in creatinine clearance than those taking TDF and an NNRTI-based regimen.(216) Creatinine clearance should be monitored more closely when TDF is used with a PI/r.

For individuals with HIV/HBV or HIV/HCV coinfection it is recommended to monitor hepatic enzymes at weeks 4 and 12 following ART initiation if feasible.