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Microbes & Immunity                                            Oxidative toxicity and folate in HIV on DTG-ART



            controls was younger adults aged 19–28  years (64.9%),   only a minimal short-term effect of DTG initiation on
            the largest proportion of PLWH on DTG-based ART were   folate status.
            in the 39–48 age category (37.8%), suggesting that HIV-  However, when compared with HIV-negative controls,
            positive individuals tended to be older.           who had substantially higher folate levels (11.11 ±
              Educational attainment was comparable between    1.31 ng/mL), both pre- and post-treatment HIV-positive
            groups  (p=0.715),  with  secondary  education  being  the   participants  exhibited  severe  folate  depletion  (p<0.001).
            most frequent, followed by tertiary and primary education.   This pattern highlights that folate deficiency is a persistent
            Socioeconomic status was also similar (p=0.601), with   feature of HIV infection, independent of immediate DTG
            over 70% of participants in both groups classified as low-  exposure.
            income status, and only a minority reporting middle- or   The effect size plot with dashed lines marking thresholds
            high-income  status.  In  contrast,  occupational  status   for small, medium, and large effects. It illustrates that
            differed significantly (p=0.001): a majority of HIV-positive   folate shows an extremely large decrease, while MDA
            participants were traders (56.8%), while nearly half of the   shows moderate-to-very large increases depending on the
            control groups were civil servants (45.9%). Marital status   comparison.
            distribution showed no significant variation between   To  complement  significance testing, Cohen’s  d  effect
            groups (p=0.348), with both groups having a predominance   sizes were calculated (Table 2 and Figure 1).
            of married individuals.
                                                                 Within the groups (pre vs. post), the increase in MDA
              These findings suggest that, while educational and   from baseline to post-treatment corresponded to a medium-
            socioeconomic backgrounds were largely balanced across   to-large effect (d = 0.74). In contrast, the decline in folate
            groups,  the  HIV-positive  cohort  was  slightly  older  and   corresponded to a small-to-medium effect (d = 0.32).
            more commonly engaged in trading, whereas controls
            were more likely to be in formal employment.         Between the groups (HIV vs. controls), very large to
                                                               extremely large effects were observed for MDA, with values
            3.2. Biochemical outcomes                          of d = 1.78 for pre versus control and d = 2.18 for post

            A significant increase in MDA levels was observed after   versus control. For folate, the differences were extremely
            24 weeks of DTG-based ART (Table 2). Mean plasma MDA   large and negative, reflecting markedly lower levels in HIV
            concentrations rose from 5.72 ± 3.61 µmol/L at baseline to   patients compared to controls; specifically, d = −6.25 for
            8.94 ± 5.03 µmol/L post-treatment (t = 2.767, p=0.009),   pre versus control and d = −9.25 for post versus control.
            reflecting a pronounced elevation in oxidative stress after   These findings provide additional insight into the
            therapy.                                           magnitude of observed biochemical alterations. The within-
              Comparison with  HIV-negative  controls  further   group effect of DTG on oxidative stress was moderate-to-
            underscored the burden of oxidative imbalance. Mean   large,  suggesting that treatment  contributed  to further
            MDA levels in the control group were markedly lower (1.19   increases  in  lipid peroxidation  beyond  baseline  HIV-
            ± 0.18 µmol/L), and both pre- and post-treatment values   associated levels. Conversely, the within-group decline in
                                                               folate was small and not statistically significant, indicating
            in the DTG group were significantly elevated relative to   that folate depletion is more strongly attributable to HIV
            controls (p<0.001).
                                                               infection itself rather than short-term DTG use. However,
              Folate levels did not show a statistically significant   the between-group comparisons revealed extremely large
            within-group change over 24 weeks of therapy (p=0.753).   differences in folate status, demonstrating the severity of
            Mean plasma folate decreased from 2.23 ± 1.52 ng/mL at   micronutrient deficiency among PLWH relative to HIV-
            baseline to 1.86 ± 0.54 ng/mL post-treatment, suggesting   negative individuals.

            Table 2. Mean values of malondialdehyde and folate among treatment‑naïve, treatment‑experienced, and control participants
            with Cohen’s d effect sizes
            Parameter    Control  Pre‑DTG Post‑DTG  p (Pre vs.  p (Pre vs.  p (Post vs.  Cohen’s d (pre vs.  Cohen’s d   Cohen’s d
                                                 post)  control)  control)  post)  (pre vs. control)  (post vs. control)
            Malondialdehyde  1.19±0.18 5.72±3.61 8.94±5.03  0.009  <0.001  <0.001  0.72   1.66 (very large ↑) 1.94 (very large ↑)
            (µmol/L)                                                  (moderate-large ↑)
            Folate (ng/mL)  11.11±1.31 2.23±1.52 1.86±0.54  0.753  <0.001  <0.001  0.29 (small ↓)  6.8 (huge ↓)  8.2 (huge ↓)
            Note: Data are expressed as means±standard deviations.
            Abbreviation: DTG: Dolutegravir.


            Volume 2 Issue 4 (2025)                        126                           doi: 10.36922/MI025310074
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