The likelihood of developing an adverse drug reaction was highest in the first six months of commencing antiretroviral therapy. Xavier et al. [4
] proffered an explanation that early occurrence of ADRs is an expression of a mechanism of intrinsic intolerance rather than of a time-dependent toxic accumulation process. Close monitoring of patients within this time frame is thus imperative to prevent the occurrence of severe ADRs, improve adherence as well as improve documentation of ADRs. However 45% of the reported ADRs occurred within 12-24 months of commencing ARVs. This calls for the need to intensify long term ADR monitoring in patients on ARV. Some studies have proposed time-dependent toxic accumulation as the mechanism of developing an ADR long after commencing medication. Thus monitoring for ADR should be an ongoing process as we have both early onset and late onset ADRs. Adding a laboratory component to the ADR screening would go a long way in determining biochemical markers that would help to improve patient management. However from a programmatic aspect in a resource constrained environment, having sound knowledge of the risk factors or common ADRs associated with different ARV regime can help focus scarce resources to managing ADRs in these settings.
Since adverse drug reactions are the single most common reason for poor adherence to treatment, identifying risk factors for the occurrence of ADRs is of crucial importance to optimize the initial choice of ARVs regimen before initiating therapy and to adapt the pace of surveillance to each unique situation [4
]. Our study showed no difference in reported ADR between men and women, however Bonfati et al [7
]. observed that women experienced significantly greater number of adverse effects compared to men. Though the population of patients on tenofovir based regimen was small compared to AZT and d4T, our data shows that patients on AZT or d4T were less likely to report an ADR than those on TDF. A multisite trial in Africa, found tenofovir therapy to be associated with 1.3% rate of significant nephrotoxicity which was comparable to other regimen,[5
] thus showing no significant toxicity difference between tenofovir and other regimens. This raises a sentinel sign that perhaps drug response to TDF in this setting is not in conformity with the results from other studies where drug profile of TDF has been superior over AZT and d4T. A closer look at the drug profile and toxicity of TDF is urgently needed to better understand its tolerance in patients in this setting. Furthermore, the most common side effect of tenofovir is renal impairment as measured by reduced creatinine clearance,[31
] thus as tenofovir replaces d4T as the nucleoside backbone of choice in HIV treatment, laboratories in resource poor settings must be strengthened to able to conduct this test.
Incidence of anaemia was low at 4% and occurred exclusively in patients on AZT. This is similar to other studies conducted in Nigeria, Co^ te d'Ivoire, Haiti and India that observed anaemic rates of 3%-12% [5
]. The incidence of skin toxicity (18%) is similar to that in other reports,[15
] though some reports have observed low incidence of skin toxicity,[10
] however the incidence of Steven-Johnson syndrome (1%) was similar to other reports which reported less than 5% [14
]. Most of the reported ADRs (71%) were mild to moderate and self limiting in nature while 1% were life threatening. This suggests good tolerance level to ARVs in general. While other studies have associated low CD4 count at treatment initiation as a risk factor for ADR [5
], our study did not show any association between CD4 cell count and clinical stage with ADRs.
Our study takes strength in its large sample size. This is the largest cohort of patients who have been surveyed in Nigeria for ADR using active surveillance. It also presents ADR outcomes in a large public health program and more closely presents treatment outcomes that are more generalizable than clinical studies. Finally data in this study was of good quality giving the scale of the program and its routine nature of collection. Mathieu Forster et al. [39
] assessed data quality for ART services in low income countries by evaluating the availability of six key variables (age, sex, W.H.O clinical staging at baseline and follow-up, CD4 count and year of ART initiation) and calculating the proportion of missing data to determine the quality of data and the median was found to be 10.9%. The median of the percentages of missing variables was 0% for all sites surveyed.
This study has some limitations. The study included patients who had initiated ART before active surveillance of ADR commenced. Though this provided information on long term adverse effects, we may have missed early onset ADR from these patients. The small sample size of patients on tenofovir based regimen limits our ability to compare ADR reported by this group with other regimen groups. Also the ADR screening tool was structured and thus, does not allow details of unknown ADR to be captured and graded, thus the study was confined to report on known ADRs only. Finally, not all ADRs reported had their complete details collected and graded. Thus the specific ADRs in this study are most likely under reported.