Cardiovascular Journal of Africa: Vol 30 No 6 (November/December 2019)

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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 30, No 6, November/December 2019 AFRICA 359
Inflammation may be further aggravated in the presence
of oxidative stress, which may be a consequence of both
HIV infection and ART.34 Higher levels of GGT were seen, a
liver enzyme known to play an important role in maintaining
glutathione homeostasis and normal redox status,35 along with
a greater increase in GGT over 10 years in the HIV-infected
group. Where others reported that ART lowered serum GGT in
HIV-infected patients,10 the findings of this study did not support
this, which could be attributed to the effects of the nucleosides.10
The use of GGT applies beyond oxidative stress, as it is also a
marker of non-fatty and alcohol-related liver disease.36 Although
self-reported alcohol use was high in our study, it did not differ
between these groups.
Together with GGT, higher ALT and AST levels were
reported at follow up and an increase in ALT over time
in the HIV-infected participants compared to a decrease in
uninfected counterparts. These results are in agreement with
previous findings.10 It should be noted, however, that ALT
and GGT levels were not above the cut-off values of 40 and
50 U/l, respectively, for liver disease.37,38 Administration of
NRTIs is associated with mitochondrial toxicity, while NNRTIs
are metabolised by the cytochrome P450, known to increase
activities of co-administered ART and hence elevating the toxic
effect on the hepatocytes.39 As the HIV-infected participants
will continue ART, it is expected that these liver enzymes will
increase further over time, which warrants regular monitoring
of liver function in the future.
In those with HIV, higher uACR and lower eGFR at baseline
was indicated, while over 10 years, eGFR increased. This increase
in eGFR is contrary to the normal expectations of a decrease
with aging,23 but aligns well with the findings of the Multicenter
AIDS Cohort Study where an increase in eGFR in HIV-infected
patients was defined as hyperfiltration (eGFR ≥ 140 ml/min/1.73
m2).40 This finding may indicate renal deterioration and may in
future lead to the observed higher prevalence of renal failure in
HIV-infected populations.11 However, in this study the eGFR
was not above the cut-off value as proposed by the Multicenter
AIDS Cohort Study.
This increase for eGFR may also suggest a catch-up effect in
renal function over time due to ART. Renal impairment occurs
dependent or independent of HIV infection. In the former pattern,
HIV alters renal function as a result of immune suppression and
when ART is introduced, renal function improves by exerting its
antiviral effects.41 In the latter pattern, patients have improved
immune function due to long-term ART use, which later results
in nephrotoxicity, or as a result of pre-existing renal impairment
and aging.42 Although the renal function markers did not
indicate renal disease over time, it is important that regular renal
screening be done as this HIV-infected cohort is ageing and using
life-long ART.
The findings of this study should be interpreted in the
context of the strengths and limitations of our study design.
Demographic and cardiometabolic profiling of HIV-infected
and control participants were carefully performed over a
period of 10 years, thereby contributing to longitudinal data
in Africans living with HIV. HIV-infected participants (n =
20) that were newly diagnosed during the follow-up studies
were also included. Regarding ART information, ART use was
not available for 26 HIV-infected participants. Although this
study is limited by a relatively small sample size, it is overcome
somewhat by the longitudinal design of the study, but may
not be representative of the HIV-infected population of South
Africa.
Conclusion
SouthAfricans living withHIV for 10 years presentedwith similar
changes in blood pressure and body composition compared
to their uninfected counterparts. However, HIV infection
was accompanied by longitudinal changes in the lipid profile,
which may indicate the future development of dyslipidaemia.
Low-grade inflammation and oxidative stress are common in
HIV-infected individuals using ART, and the changes seen may,
together with the lipid changes, reflect the development of a
pro-atherogenic profile, which is associated with increased risk
of CVD. In addition, the trajectories of increased CRP levels,
elevated liver enzymes and increased eGFR should be carefully
monitored in light of HIV infection and ART use.
The authors are grateful to all participants who voluntarily took part
in the study, the PURE-SA research team and the field workers, North-
West University, South Africa, as well as Prof Lanthé Kruger (PURE
South Africa), Dr S Yusuf (PURE International), the PURE project team
at Hamilton Health Sciences at the McMaster University, ON, Canada,
the South African Medical Research Council and the National Research
Foundation, Department of Science and Technology, and Servier Medical Art.
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