The study showed that relatively few patients had abnormal results on the tests used for screening for ART eligibility in South Africa. The prevalence of abnormal tests may be even lower among the relatively more healthy cohorts who are initiating ART presently, given that all HIV-infected patients are now eligible for ART, regardless of CD4 count. In particular, our findings raise questions about the utility of routine creatinine clearance testing before initiating TDF in our setting. Significant renal dysfunction was very uncommon in our study, as measured by creatinine clearance, although microalbuminuria was relatively frequent. As further data accrues on this topic, ART guideline committees could consider minimising the number of tests done to identify relative and absolute contraindications to the use of certain antiretrovirals. Alternatively, future guideline iterations may consider continuing the screening tests, but recommending that ART could be initiated while waiting for the results and then patients regimens be altered at the subsequent visit, if required.
Findings from several other South African cohorts on creatinine clearance have been conflicting, with most also reporting low levels of renal dysfunction, but a few recording abnormal results in as many as 5% of patients initiating antiretrovirals [15,16,17]. All these findings, however, are far lower than other reports from the rest of the continent [3, 18]. The urine abnormalities at ART initiation may reflect concurrent illness, rather than renal dysfunction per se; in addition, some renal dysfunction may not be measured by creatinine clearance. Moreover, a retrospective record review in 2014 in Lusaka, looking at patients who initiated TDF while having renal dysfunction, suggested that most patients with moderate to severe abnormal creatinine clearances do not experience deterioration of renal function on TDF . Similarly, previous data from a study in our site suggest that most urine abnormalities tend to normalise over time . Based on the above factors, we contend that renal screening with urine dipstick or creatinine clearance may add little to patient management in our setting, and unnecessarily delay ART initiation, while increasing programme complexity and cost. Prospective analysis of the treated cohort described here, where proteinuria and microalbuminuria will be followed over time, may help confirm that assertion.
Hepatitis B infection was common, in keeping with previous reports, both from the general population, as well as from other HIV clinics in South Africa [21,22,23]. It is unclear how commonly hepatic flares or withdrawal hepatitis occurs with ART , as currently data are limited to isolated case reports [10, 11]. Moreover, is it uncertain how much routine screening would assist in mitigating these clinical outcomes. Significant AST and ALT abnormalities were very rare at baseline; and the predictive power of these tests for flares or withdrawal hepatitis is unknown. The rationale for screening for hepatitis virus is unclear to us.
Mild anaemia was very common, but significant anaemia (<8 g/dl), the threshold suggested in local guidelines as a contraindication to AZT, was very unusual, in keeping with other studies [24, 25]. In addition, neutropaenia was uncommon. This suggests that AZT may be used relatively safely in this group, without screening, although the role of the drug in resource-limited settings outside of second regimens is now largely confined to those with renal disease [2, 6].
Limitations of the study include the difficulties in generalising the findings to South Africa as a whole, given the urban nature and high percentage of Zimbabweans in the screened population. The findings, however, might apply to similar inner-city areas of the country, or even to parts of Zimbabwe. Also, participants in this study were on average relatively young and the creatinine clearance abnormalities may be more frequent among older patients. Excluding patients with peripheral neuropathy or exposure to antiretroviral drugs for preventing mother-to-child transmission of HIV may also limit generalisability of results, although unlikely to any meaningful degree. The use of community workers to identify potential participants, rather than using systematic sampling, may have incurred selection bias. Community workers could, for example, have been more likely to approach patients they knew, those of the same gender as themselves, or those they believed would be more likely to participate. Having been instructed to refer patients with a CD4 below 400 may have resulted in them purposely recruiting sicker looking patients. Finally, hepatitis B was screened using antigen testing, which may miss occult HBV infections [23, 26] and cases of delta virus, though the latter is very rare in South Africa [22, 27].