Box 7.2: Surveillance of ARV drug toxicity

Consolidated ARV guidelines, June 2013

WHO commissioned systematic reviews on specific types of toxicities associated with key ARV drugs and laboratory monitoring strategies to consolidate and update technical guidance (140,169). The reviews highlighted remaining evidence gaps in the potential increased risk of toxicity associated with the long-term use of ARV drugs, the use of ARV drugs during pregnancy and in breastfeeding mothers, children and adolescents and populations with associated risk factors and in laboratory monitoring for toxicity.

The available evidence is limited to studies with limited sample size or short duration. It is essential to monitor the use of ARV drugs in resource-limited countries where toxicities may present a different pattern in association with environmental or behavioural factors, the prevalence of other conditions and where ARV drugs are used in association with other medicines. Implementing toxicity surveillance will provide the opportunity to produce evidence on specific types of toxicity, increase confidence in the use of the drugs, identify populations with risk factors and plan preventive strategies.

The Guidelines Development Group encouraged WHO to strengthen toxicity surveillance activities to increase evidence on toxicity in key areas. These areas cover a potential increased risk of toxicity associated with the long-term use of ARV drugs, renal and bone toxicity associated with using TDF among adults and children, the safety of using EFV- and TDF-containing regimens during pregnancy and in breastfeeding mothers and using TDF among children, adolescents and populations with associated risk factors. Developing laboratory markers to monitor renal function among people using TDF is another important area for research.

Several toxicity surveillance activities have already started with WHO support, using standardized approaches at sentinel sites in resource-limited settings. Targeted and systematic surveillance is being conducted in Côte d’Ivoire to monitor renal toxicity associated with TDF in first- and second-line regimens, with an assessment of laboratory monitoring needs in three sentinel sites. A similar approach is being implemented in Viet Nam to assess renal toxicity associated with TDF and central nervous system toxicity associated with EFV in people who use ARV drugs to prevent HIV infection, such as in serodiscordant couples. In the Lao People’s Democratic Republic, anaemia associated with AZT and hypersensitivity associated with NVP are monitored using a targeted and systematic surveillance approach. In Malawi, a surveillance programme will monitor infant growth, following mothers who are breastfeeding and receiving TDF.

The implementation of a pregnancy registry, including a surveillance programme for birth defects, is recommended where feasible to assess the safety of ARV drugs and any other medicines during pregnancy and risk factors for adverse pregnancy outcomes, including maternal health outcomes, premature births, stillbirths, low birth weight and congenital abnormalities. WHO, the United States President’s Emergency Plan for AIDS Relief, the United States Centers for Disease Control and Prevention and the United States National Institutes of Health support the establishment of ARV pregnancy registries and birth defect surveillance in sentinel sites in Malawi, South Africa and Uganda to assess the use of EFV-containing regimens at large scale among pregnant women.

Surveillance of ARV drug toxicity will help to better understand the long-term risk of ART toxicity and optimize the management of ARV drugs for HIV treatment and prevention in all populations.