TABLE 3.
Damage score (mean ± SE) |
||
NRTI exposure | At birth | At 1 year |
None | 1.6 ± 0.33 (n = 5) | 1.6 ± 0.04 (n = 4) |
AZT | NS | 2.4 ± 0.23 (n = 4) |
3TC | 2.8 ± 0.48 (n = 3) | NS |
AZT/3TC | 3.2 ± 0.44b (n = 3) | 2.6 ± 0.15b (n = 4) |
AZT/ddI | 3.4 ± 0.29b (n = 3) | 3.0 ± 0.27b(n = 4) |
d4T/3TC | 2.8 ± 0.38b (n = 3) | 2.5 ± 0.47b (n = 4) |
Note. NS, no sample.
Scoring paradigm for mitochondrial status in brain cortex: (0) = nearly all mitochondria possessed an intact membrane, compact, well-defined cristae, and a dark matrix, whereas an infrequent mitochondrion showed less definitive cristae and a lighter matrix (that were considered to be within normal limits), and the rough endoplasmic reticulum (if visible) was uniform and compressed; (+1) = majority of mitochondria were intact, and although a few possessed discontinuous membranes, no loss of cristae material, matrical density, or irregularity in endoplasmic reticulum or golgi apparatus was apparent; (+2) = an increasing number of mitochondria were dissolved with membrane disruptions but minimal loss of cristae and matrical density, whereas most of the remaining mitochondria looked essentially normal but did display disruption in endoplasmic reticulum and golgi apparatus structure; (+3) = majority of mitochondria possessed membrane disruptions, partial loss of cristae material, and elevated matrical lucency along with widespread, distention, and increased lucency surrounding the mitochondria; (+4) = nearly all mitochondria possessed dissolved membranes and loss of cristae and matrical structure, along with swelling, disorganization, and increased lucency of the surrounding structures; (+5) = in many areas, the mitochondrial membrane was completely dissolved and the cristae were fragmented and disorganized; in other areas, mitochondria containing no central architecture were apparent, and all other areas looked like those in samples graded (+4).
Values (in bold) for groups exposed to the two NRTI combinations were significantly different from the corresponding unexposed control group for monkeys taken at birth (p = 0.024) and at 1 year of age (p = 0.025) by one-way ANOVA. At birth, the Holm-Sidak method for multiple comparisons showed significance (p < 0.05) for control versus AZT/3TC, control versus AZT/ddI, and control versus d4T/3TC. At 1 year of age, the Holm-Sidak method for multiple comparisons showed significance (p < 0.05) for control versus AZT/ddI, as well as marginal significance (p < 0.06) for control versus AZT/3TC and control versus d4T/3TC.