Table 1 Review of studies that have assessed the effect of CNS penetrating ARTs on NP performance and/or on CSF HIV RNA
Author & date | What | Samples | HIV Disease | Design | Findings | Quality scoring > 80% * | < 80% Quality scoring Main factors | POWER > 80% |
|---|---|---|---|---|---|---|---|---|
Antinori et al., 2002 [25] | CSF 39% detectable viral load at baseline | 75 advanced HIV+ individuals 37% naive 29 advanced HIV+ individuals | 39% AIDS Median current CD4: 131 | Cross-sectional Longitudinal Initiating cART or new cART/retest mean: 11 weeks | Indinavir associated with greater HIV RNA suppression in the CSF Greater CSF HIV RNA suppression with 3 or more CNS penetrant ARTs | No | Clinical groups heterogeneous with multiple types of CNS HIV-related disorders IVDU risk factor in 40% | - |
Chang et al., 2003 [26] | NP tests CSF 97% detectable viral load MRS | 33 HIV+ individuals all ART naïve 19 with HAD | Mean current CD4: 182 | Longitudinal 3 months follow-up NP tests MRS | Better NP performance in individuals on 2 CNS penetrant drugs on 2 NP tests No correlation between number of CNS penetrant ARTs and reduction in MRS abnormalities. | Yes | - | No |
Cysique et al., 2004 [27] | NP tests | 97 advanced HIV+ individuals on long-term CART (average 5 years) 100% AIDS | Mean Nadir CD4: 73 Mean current CD4: 369 | Cross sectional | Better performance in Learning and memory when on a CART regimen with = > 3 neuroactive agents in NP impaired (N = 26) | Yes | - | No |
Cysique et al, 2006 [28] | NP tests | 81 advanced HIV+ individuals on long-term CART (average 5 years) 100% AIDS | Mean Nadir CD4: 73 Mean current CD4: 385 | Longitudinal Yearly for an average of 27 months | Improvement on Psychomotor speed on a CART regimen with = > 3 neuroactive agents | No | Inclusion/exclusion criteria not readily available; NeuroHAART definition not readily available | - |
Author & date | What | Samples | HIV Disease | Design | Findings | Quality scoring > 80% * | < 80% Quality scoring Main factors | POWER > 80% |
Cysique et al. 2009 [29] | NP tests CSF 85% detectable at baseline | 37 HIV+ individuals with mild to moderate HAND Initiated on CART 38% ART naïve | Means Nadir CD4 = 106 Baseline CD4 = 195 AIDS 77% | Longitudinal Every 12 weeks for 48 weeks | Overall improvement in cognitive functions with higher CPE | Yes | - | No |
De Luca et al., 2002 [30] | CSF Median log 10 CSF HIV RNA: 2.9 | 95 HIV+ individuals On cART 50 HIV+ individuals On cART | Median current CD4: 110 Median current CD4: 59 | Cross-sectional Longitudinal Follow-up median of 7 weeks | Higher number of CNS penetrant ARTs correlated with lower CSF HIV RNA (trend only). Greater longitudinal decrease in CSF HIV RNA associated higher number of CNS penetrant | No | Clinical groups heterogeneous with multiple types of CNS HIV-related disorders IVDU risk factor in 30-40% | - |
Eggers et al., 2003 [31] | CSF 80% detectable at baseline | 40 HIV+ individuals 10 with HIVE 8 with HAD | Median current CD4: 60 29% CDC stage C | Longitudinal LP prior and after cART initiation Unclear time-frame | No correlation between the number of CNS penetrant drugs and slope of CSF viral decay. | No | Definition of HAND using brief screens Clinical groups heterogeneous | - |
Marra et al., 2003 [32] | NP tests CSF 75% detectable at baseline | 25 HIV+ individuals HAND baseline rate? | Mean current CD4: 259 | Longitudinal Testing before CART initiation at 4 & 8 weeks after Comparison of regimen containing AZT & IDV to other regimen | Improved on 4 NP tests associated with VL suppression in the CSF in ART naïve (but not 8 weeks) No significant change in CSF viral load. | No | Small test battery Unclear inclusion/exclusion criteria Unclear baseline level of NP-impairment No adequate normative data No practice effect correction | - |
Author & date | What | Samples | HIV Disease | Design | Findings | Quality scoring > 80% * | < 80% Quality scoring Main factors | Â |
Marra et al., 2009 [33] | NP tests CSF Median log 10 CSF HIV RNA at baseline: 3.3 | 101 HIV+ individuals initiating or changing cART | Median CD4: 111 | Longitudinal Follow-up at 24 and 52 weeks ACTG 736 | Odds of suppression of CSF HIV RNA were higher when CPE rank was = > 2 (N = 79) Impaired HIV+ individuals on a cART with a CPE = > 2 had worse NP performance over time (N = 26) on NP 4 tests, but not 8 NP tests. | No | Unclear inclusion/exclusion criteria Short NP testing battery Lack of education and racial correction in NP tests relevant to the study population | - |
Letendre et al., 2004 [34] | CSF Mean log 10 CSF HIV RNA at baseline: 4.1 | 31 HIV+ with mild to moderate HAND | 81% AIDS Means nadir Cd4: 30 Current CD4: 111 | Longitudinal Testing before & 15 months after CART initiation | Greater CSF HIV RNA reduction with higher number of CNS penetrant ARTs | No | Unclear study time points No control for practice effect Correlational analyses only No practice effect correction | - |
Letendre et al., 2008 [35] | CPE CSF 17% detectable at baseline | 467 HIV+ individuals on cART 389 Undetectable and 78 Detectable | 77% AIDS Medians nadir CD4: 116 current CD4: 406 | Cross-sectional Validation of the CPE index | CPE < 2 associated with an 88% increase in the odds of detectable CSF viral load CPE ranks were associated with detectable CSF viral loads with and without treatment and disease adjustments | Yes | - | No |
Patel et al., 2009 [36] | Survival time | 2398 HIV+ children 77 incident HIVE [incidence rate 5.1 cases per 1000 person-years. | CD4% ≤ 15%: 19% | Longitudinal Median 6.4 years AACT219/219C | High CNS-penetrating regimens associated with a survival benefit (74% reduction in the risk of death, 95% CI 39-89%) after HIVE diagnosis compared with low CNS-penetrating regimens | No | Clinical groups heterogeneity Clinical diagnoses as outcome No NP assessment | - |
Author & date | What | Samples | HIV Disease | Design | Findings | Quality scoring > 80% * | < 80% Quality scoring Main factors | Â |
Sacktor et al., 2001 [37] | NP tests | 18 in single in CSF penetrant group 55 in multiple CSF penetrant group With psychomotor slowing 6-7% HAD | 11%-31% AIDS Mean current CD4: 339-255 | Longitudinal Six annual study visit cART initiation | No difference in NP improvement between 2 groups. | No | Unclear inclusion/exclusion criteria NeuroHAART definition not readily available Short NP battery | - |
Sevigny et al., 2004 [38] | Incident HAD | 203 advanced non-demented HIV+ individuals 73% on cART | Median current CD4: 127 | Longitudinal Median follow-up of 21 months 36% with incident HAD | Regimens containing = > CNS penetrant ARTs was not associated with time to HAD | No | Clinical groups heterogeneity Ad hoc analyses of time to HAD Time to HAD not a validated measure of NP change | - |
Smurzynski et al., 2011 [39] | NP tests | 2636 HIV+ individuals at least 6 weeks on cART | Median current CD4: 243 Nadir CD4: 182 | Longitudinal Median follow-up of 4.7 years CPE rank score & ARTs in cART Neuroscreen: 3 NP tests | When cART was composed of more than 3 ARTs there was a positive association between CPE and better NP performance in unadjusted and adjusted models. | Yes | Â | Yes |
Tozzi et al., 2009 [40] | NP tests | Patients with (n = 93) or at risk for (n = 92) HIV-associated neurocognitive disorders | 37% stage CDC C Mean current CD4: 292 Nadir CD4: 181 | Cross-sectional Longitudinal NP testing before and after cART initiation (20 months mean interval) Comparison of 2 "neuropenetration" scores (CPE vs. numbers) | Higher CPE correlated with better NP performance at baseline and follow-up, but not using the number of CNS penetrant drugs | Yes | - | Yes |