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 |
|
| 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 |
|
| 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 | 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 |
NB: italicized font: beneficial effect of NeuroHAART on NP performance and or CSF HIV RNA reduction
Regular font: neutral effect of the NeuroHAART,
Bold front: negative effect of NeuroHAART.
ARTs: Antiretrovirals
LP: lumbar puncture
HIVE: HIV encephalopathy
MRS: Magnetic Resonance Spectroscopy
MND: Minor motor Deficits
MSK: Memorial Sloan Kettering
NP: neuropsychological
A score less than or equal to 80% meant that a study presented at least three or more methodological limitations.