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BACKGROUND: Randomized control studies have not shown an association between treatment with tenofovir (TDF) and clinically significant kidney toxicity. However, multiple cases of renal tubular toxicity have been described in patients with HIV treated with TDF. It is unclear whether spot urine protein- or albumin-creatinine ratio is a sufficiently sensitive screening test to detect subclinical renal tubular toxicity in patients with HIV. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: 99 patients with HIV with serum creatinine levels < 1.70 mg/dL and dipstick-negative proteinuria; 19 were antiretroviral treatment (ART) naive, 47 were on a TDF regimen, and 33 were on ART, but with no history of TDF exposure. PREDICTOR OR FACTOR: Exposure to TDF. OUTCOMES: Spot urine concentrations of retinol-binding protein (RBP; a low-molecular-weight protein normally reabsorbed by the proximal tubule), N-acetyl-beta-D-glucosaminidase (NAG; a proximal tubule lysosomal enzyme), albumin (A; a marker of glomerular disease), and protein (P; a standard clinical screening test for kidney pathological states) expressed as a ratio to creatinine (C; U(RBP/C), U(NAG/C), U(A/C), and U(P/C), respectively). RESULTS: There were no significant differences in median U(A/C) (ART-naive, 7.3 mg/g [range, 0-245.8 mg/g]; TDF, 9.0 mg/g [range, 0.1-184.1 mg/g]; and non-TDF, 10.5 mg/g [range, 2.6-261.6 mg/g]; P = 0.8). U(RBP/C) excretion was significantly higher in the TDF group (median, 214.2 microg/g [range, 26.8-17,454.5 microg/g]) than in the ART-naive group (92.5 microg/g [range, 21.3-3,969.0 microg/g]; P = 0.03); there was also a trend toward higher values than in the non-TDF group (111.6 microg/g [range, 31.0-6,136.3 microg/g]; P = 0.08). U(NAG/C) excretion was significantly higher in both the TDF (median, 394.7 micromol/h/g [range, 140.5-10,851.3 micromol/h/g]; P = 0.01) and non-TDF (406.8 micromol/h/g [range, 12.4-8,485.8 micromol/h/g]; P = 0.03) groups compared with the ART-naive group (218.6 micromol/h/g [range, 56.5-2,876.1 micromol/h/g]). U(P/C) was significantly higher in the TDF (median, 123.9 mg/g [range, 53.1-566.4 mg/g]) than the non-TDF group (97.3 mg/g [range, 0-451.3 mg/g]; P = 0.03). The proportion of patients with evidence of tubular dysfunction (increased U(RBP/C) and/or U(NAG/C)) was considerably higher than the proportion with an increase in U(A/C) or U(P/C) in all groups: for ART-naive, 52.6% vs 31.6% vs 25.0%; for TDF, 80.9% vs 29.8% vs 52.2%; and for non-TDF, 81.8% vs 39.4% vs 30.0%. The level of agreement among the different urinary test results was low. LIMITATIONS: Causality cannot be established from single measurements of urinary markers in a cross-sectional study. CONCLUSIONS: Patients with HIV had high rates of subclinical proteinuria, but neither U(P/C) nor U(A/C) is sufficiently sensitive alone to detect many of these cases. Patients using TDF have increased U(RBP/C) and U(P/C); the significance of this will need to be determined from longer-term outcome studies. [ABSTRACT FROM AUTHOR]

An unmatched retrospective case control study was conducted to test the feasibility of investigating social and behavioural factors which may have contributed to recent HIV seroconversion in a group of homosexual men. Participants, recruited from a London sexually transmitted disease (STD) clinic, were sexually active and had had a negative HIV test with a subsequent test (positive (cases) or negative (controls)) within three to 15 months. Twenty cases and 22 controls were recruited between February and October 1995. There was no difference between cases and controls in: the number of regular or casual sexual partners, the proportion who were unaware of their regular partners' serostatus (cases 60%, controls 59%), or the proportion who had known HIV-positive regular partners (cases 20%, controls 23%). A significant difference in sexual behaviour was found only when the HIV status of partners, if known, was taken into account: cases were more likely than controls to have had unprotected receptive anal intercourse with a partner not known to be HIV-negative (OR = 5.5, CI = 1.15-29.50). Fifty per cent of the cases and 27% of the controls acquired acute STDs between the two HIV tests. All participants achieved high self-efficacy scores, but the controls believed their peers placed a greater value on safer sex. Cases cited emotional issues and the use of drugs and alcohol as contributing to their seroconversion, whereas controls cited a commitment to safer sex and the avoidance of high-risk situations as contributing to their remaining HIV-negative. The results illustrate the importance of acknowledging the concept of 'negotiated safety' in studies of sexual behaviour; seroconversion was only associated with unprotected sex with a partner not known to be HIV-negative. Despite high self-efficacy scores, indicating the skills to negotiate safer sex, high levels of unsafe anal intercourse were reported. Differences between cases and controls included the importance of safer sex, periods of emotional vulnerability, influence of peers and the appropriate use of condoms. There is a need for these results to be confirmed in a larger and more powerful study. [ABSTRACT FROM AUTHOR]

Metal cations have been exploited for their precipitation properties in a wide variety of studies, ranging from differentiating proteins from serum and blood to identifying the protein targets of drugs. Despite widespread recognition of this phenomenon, the mechanisms of metal-induced protein aggregation have not been fully elucidated. Recent studies have suggested that copper's (Cu) ability to induce protein aggregation may be a main contributor to Cu-induced cell death. Here, we provide the first proteome-wide analysis of the relative sensitivities of proteins across the Escherichia coli proteome to Cu-induced aggregation. We utilize a metal-induced protein precipitation (MiPP) methodology that relies on quantitative bottom-up proteomics to define the metal concentration-dependent precipitation properties of proteins on a proteomic scale. Our results establish that Cu far surpasses other metals in promoting protein aggregation and that the protein aggregation is reversible upon metal chelation. The bulk of the Cu bound in the protein aggregates is Cu1+, regardless of the Cu2+ source. Analysis of our MiPP data allows us to investigate underlying biophysical characteristics that determine a protein's sensitivity to Cu-induced aggregation, which is independent of the relative concentration of protein in the lysate. Overall, this analysis provides new insights into the mechanism behind Cu cytotoxicity, as well as metal cation-induced protein aggregation., (© The Author(s) 2022. Published by Oxford University Press.)

We assessed whether HIV status was associated with white matter hyperintensities (WMH), a neuroimaging correlate of cerebral small vessel disease (CSVD), in men aged ≥50 years. A cross-sectional substudy was nested within a larger cohort study. Virologically suppressed men living with HIV (MLWH) and demographically matched HIV-negative men aged ≥50 underwent magnetic resonance imaging (MRI) at 3 Tesla. Sequences included volumetric three-dimensional (3D) T1-weighted, fluid-attenuated inversion recovery and pseudocontinuous arterial spin labeling. Regional segmentation by automated image processing algorithms was used to extract WMH volume (WMHV) and resting cerebral blood flow (CBF). The association between HIV status and WMHV as a proportion of intracranial volume (ICV; log-transformed) was estimated using a multivariable linear regression model. Thirty-eight MLWH [median age 59 years (interquartile range, IQR 55-64)] and 37 HIV-negative [median 58 years (54-63)] men were analyzed. MLWH had median CD4 + count 570 (470-700) cells/μL and a median time since diagnosis of 20 (14-24) years. Framingham 10-year risk of cardiovascular disease was 6.5% in MLWH and 7.4% in controls. Two (5%) MLWH reported a history of stroke or transient ischemic attack and five (13%) reported coronary heart disease compared with none of the controls. The total WMHV in MLWH was 1,696 μL (IQR 1,229-3,268 μL) or 0.10% of ICV compared with 1,627 μL (IQR 1,032-3,077 μL), also 0.10% of ICV in the HIV-negative group ( p  = .43). In the multivariable model, WMHV/ICV was not associated with HIV status ( p  = .86). There was an age-dependent decline in cortical CBF [-3.9 mL/100 mL/min per decade of life (95% confidence interval 1.1-6.7 mL)] but no association between CBF and HIV status ( p  > .2 in all brain regions analyzed). In conclusion, we found no quantitative MRI evidence of an increased burden of CSVD in MLWH aged 50 years and older.

Background: Protease inhibitor monotherapy (PIM) for human immunodeficiency virus (HIV) may exert suboptimal viral control in the central nervous system. We determined whether cerebral blood flow (CBF) and regional brain volumes were associated with PIM, and whether specific cognitive domains were associated with imaging biomarkers., Methods: Cognitive assessments and brain magnetic resonance imaging were performed after the final visit of a randomized HIV-treatment strategy trial. Participants were virologically suppressed on triple therapy at trial entry and followed for 3-5 years. We studied 37 patients randomized to ongoing triple therapy and 39 randomized to PIM. Resting CBF and normalized volumes were calculated for brain regions of interest, and correlated with treatment strategy and neuropsychological performance., Results: Mean age was 48.1 years (standard deviation 8.6 years), 63 male (83%), and 64 white (84%). Participants had median 8.1 years (interquartile range 6.4, 10.8) of antiretroviral therapy experience and CD4+ counts of median 640 cells/mm3 (interquartile range 490, 780). We found no difference between treatment arms in CBF or regional volumes. Regardless of treatment arm, poorer fine motor performance correlated with lower CBF in the caudate nucleus (P = .01), thalamus (P = .04), frontal cortex (P = .01), occipital cortex (P = .004), and cingulate cortex (P = .02), and was associated with smaller supratentorial white matter volume (decrease of 0.16 in Z-score per -1% of intracranial volume, 95% confidence interval 0.02-0.29; P = .023)., Conclusions: PIM does not confer an additional risk of neurological injury compared with triple therapy. There were correlations between fine motor impairment, grey matter hypoperfusion, and white matter volume loss., Clinical Trials Registration: ISRCTN-04857074., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Context: Therapies to decrease immune activation might be of benefit in slowing HIV disease progression., Objective: To determine whether hydroxychloroquine decreases immune activation and slows CD4 cell decline., Design, Setting, and Patients: Randomized, double-blind, placebo-controlled trial performed at 10 HIV outpatient clinics in the United Kingdom between June 2008 and February 2011. The 83 patients enrolled had asymptomatic HIV infection, were not taking antiretroviral therapy, and had CD4 cell counts greater than 400 cells/μL., Intervention: Hydroxychloroquine, 400 mg, or matching placebo once daily for 48 weeks., Main Outcome Measures: The primary outcome measure was change in the proportion of activated CD8 cells (measured by the expression of CD38 and HLA-DR surface markers), with CD4 cell count and HIV viral load as secondary outcomes. Analysis was by intention to treat using mixed linear models., Results: There was no significant difference in CD8 cell activation between the 2 groups (-4.8% and -4.2% in the hydroxychloroquine and placebo groups, respectively, at week 48; difference, -0.6%; 95% CI, -4.8% to 3.6%; P = .80). Decline in CD4 cell count was greater in the hydroxychloroquine than placebo group (-85 cells/μL vs -23 cells/μL at week 48; difference, -62 cells/μL; 95% CI, -115 to -8; P = .03). Viral load increased in the hydroxychloroquine group compared with placebo (0.61 log10 copies/mL vs 0.23 log10 copies/mL at week 48; difference, 0.38 log10 copies/mL; 95% CI, 0.13 to 0.63; P = .003). Antiretroviral therapy was started in 9 patients in the hydroxychloroquine group and 1 in the placebo group. Trial medication was well tolerated, but more patients reported influenza-like illness in the hydroxychloroquine group compared with the placebo group (29% vs 10%; P = .03)., Conclusion: Among HIV-infected patients not taking antiretroviral therapy, the use of hydroxychloroquine compared with placebo did not reduce CD8 cell activation but did result in a greater decline in CD4 cell count and increased viral replication., Trial Registration: isrctn.org Identifier: ISRCTN30019040.

Home delivery (HD) of medication is a goal of the Department of Health's Pharmacy in the Future; Implementing the NHS Plan. We evaluated the safety and effectiveness of an HD service for antiretroviral therapy (ART). Patients on ART with stable viral load (VL) <50 were identified. Comparison was made between patients using HD and those using the clinic-based pharmacy (CP). The primary endpoint was HIV virological failure (VF) (HIV VL >400 copies/mL on two consecutive occasions). Secondary endpoints included frequency of outpatient attendances (OPA) and an incidence of adverse events. Cumulative incidences (CulmIn) for each outcome event were calculated. Incidence-rate ratios (IRR) were obtained using Poisson regression. Of 1663 patients identified; 450 received HD and 1213 used CP. CuImIn of VF was =4% in those using HD and =7% in those using CP (IRR [95% confidence intervals, CI] =0.53, 0.32-0.90). HD patients had fewer OPA, less frequent blood test monitoring and less frequent abnormal liver function results (IRR [95% CI]= 0.63 [0.59-0.67] and 0.59 [0.53-0.67], 0.68 [0.65-0.71] and 0.64 [0.53-0.78], respectively). Patients deemed stable enough on social, psychological and medical grounds to receive HD of ART had a lower risk of VF, fewer OPA and no increase in adverse events when compared with patients using CP.

Background: We sought to investigate renal function in previously untreated symptomatic human immunodeficiency virus (HIV)-infected adults with CD4(+) cell counts of <200 cells/mm(3) who were undergoing antiretroviral therapy (ART) in Africa., Methods: The study was an observational analysis within a randomized trial of ART management strategies that included 3316 participants with baseline serum creatinine levels of < or =360 micromol/L. Creatinine levels were measured before ART initiation, at weeks 4 and 12 of therapy, and every 12 weeks thereafter. We calculated estimated glomerular filtration rate (eGFR) using the Cockcroft-Gault formula. We analyzed the incidence of severely decreased eGFR (<30 mL/min/1.73 m(2)) and changes in eGFR to 96 weeks, considering demographic data, type of ART, and baseline biochemical and hematological characteristics as predictors, using random-effects models., Results: Sixty-five percent of the participants were women. Median values at baseline were as follows: age, 37 years; weight, 57 kg; CD4(+) cell count, 86 cells/mm(3); and eGFR, 89 mL/min/1.73 m(2). Of the participants, 1492 (45%) had mild (> or =60 but <90 mL/min/1.73 m(2)) and 237 (7%) had moderate (> or =30 but <60 mL/min/1.73 m(2)) impairments in eGFR. First-line ART regimens included zidovudine-lamivudine plus tenofovir disoproxil fumarate (for 74% of patients), nevirapine (16%), and abacavir (9%) (mostly nonrandomized allocation). After ART initiation, the median eGFR was 89-91 mL/min/1.73 m(2) for the period from week 4 through week 96. Fifty-two participants (1.6%) developed severe reductions in eGFR by week 96; there was no statistically significant difference between these patients and others with respect to first-line ART regimen received (P = .94). Lower baseline eGFR or hemoglobin level, lower body mass index, younger age, higher baseline CD4(+) cell count, and female sex were associated with greater increases in eGFR over baseline, with small but statistically significant differences between regimens (P < .001 for all)., Conclusions: Despite screening, mild-to-moderate baseline renal impairment was relatively common, but these participants had greatest increases in eGFR after starting ART. Severe eGFR impairment was infrequent regardless of ART regimen and was generally related to intercurrent disease. Differences between ART regimens with respect to changes in eGFR through 96 weeks were of marginal clinical relevance, but investigating longer-term nephrotoxicity remains important.

Objective: To evaluate whether the addition of a fourth drug for up to 32 weeks to a standard three-drug antiretroviral combination decreases the risk of virological failure without increasing toxicity in treatment-naive patients., Design: Induction/maintenance (IM) therapy [two nucleoside reverse transcriptase inhibitors (NRTIs) + one non-NRTI (NNRTI) + one protease inhibitor for 24-32 weeks until plasma HIV RNA viral load (VL) < or =50 copies/ml then two NRTIs + NNRTI] was compared with standard therapy (ST) (two NRTIs + NNRTI). The primary endpoint was virological failure: VL >50 copies/ml at 32 (and 24) weeks or subsequent rebound to >400 copies/ml., Results: 122 (62 IM, 60 ST) participants were randomized and followed for a median of 81 weeks (IQR 64-145). 52% were asymptomatic; median CD4+ T-cell count was 160 x 10(6)/l (IQR 92-260) and median VL 98,830 copies/ml (IQR 37,500-241,290). In an intent-to-treat analysis, the proportion of participants with virological failure at or after 32 weeks was higher in the ST arm [26 (43%) versus 11 (18%), P = 0.002]. The mean decrease in VL at 48 weeks was 0.84 95% confidence interval (CI) (0.15, 1.53) log10 copies/ml greater in the IM arm (P = 0.02). There were no significant differences between the two arms in the change in CD4+ T-cell count from baseline to 48 weeks, the number of participants with adverse events or the frequency of progression to AIDS/death. Drug resistance at failure was detected less frequently in the IM arm., Conclusions: Starting antiretroviral therapy with an IM strategy improved virological outcomes compared with a three-drug regimen, without significantly increasing toxicity.

We develop a percolation model for nodal domains in the eigenvectors of quantum chaotic torus maps. Our model follows directly from the assumption that the quantum maps are described by random matrix theory. Its accuracy in predicting statistical properties of the nodal domains is demonstrated for perturbed cat maps and supports the use of percolation theory to describe the wave functions of general Hamiltonian systems. We also demonstrate that the nodal domains of the perturbed cat maps obey the Cardy crossing formula and find evidence that the boundaries of the nodal domains are described by stochastic Loewner evolution with diffusion constant close to the expected value of 6, suggesting that quantum chaotic wave functions may exhibit conformal invariance in the semiclassical limit.

Objectives: The study tests the hypothesis that monocyte derived dendritic cells from HIV-1 infected individuals are normal and can restore impaired CD4 T-cell antigen specific responses., Design: Monocyte derived dendritic cells were isolated from individuals at three different stages of HIV-1 infection with a wide spectrum of viral load and CD4 T-cell counts, and from healthy volunteers. The cell surface phenotype and allogeneic stimulatory potential of these dendritic cells was documented. CD4 T-cell responses to HIV p24, tetanus toxoid and purified protein derivative were measured using either unfractionated peripheral blood mononuclear cells, or purified dendritic cell/T-cell cultures., Results: Dendritic cells from all three HIV-1 infected groups did not differ from each other or from healthy volunteers in terms of cell surface phenotype or allogeneic stimulatory potential using T cells from healthy volunteers. Dendritic cells from immunosuppressed antiretroviral naive individuals enhanced the autologous recall proliferative responses both to HIV-1 p24, and third party antigens tetanus toxoid and purified protein derivative, both in terms of the proportion of responding individuals, and median proliferation., Conclusion: Antigen presentation by dendritic cells partially restores impaired antigen specific CD4 T-cell responses associated with HIV-1 infection. Immunization strategies which target dendritic cells may therefore offer significant advantages in the ability to stimulate HIV-specific protective immune responses.

We have developed a high throughput computational tool for assigning subtype to HIV-1, based solely on protease and reverse transcriptase (PR-RT) amino acid sequence, generated routinely for clinical assessment of genotypic drug resistance. Subtype-specific profiles were created by generation of position-specific scoring matrices (PSSMs) from multiple amino acids alignments of HIV-1 sequence data from GenBank, phylogenetically divided into subtypes A, AG, B, C, D, F/K, G, H, and J and the separate groups N and O. Query sequences of unknown subtype are aligned with these profiles and a score is derived by comparing each amino acid position in the unknown sequence to the normalized frequency distribution of amino acids at the corresponding positions in the subtype alignments. The highest score is used to assign subtype to the query sequence. Leave one out cross-validation analysis showed the Subtype Analyzer (STAR) was 99% accurate in subtype assignation. STAR can be updated with additional subtype-specific sequence data from sequence databases. STAR was used to classify HIV-1 PR-RT sequences from 843 HIV-1 clinical isolates submitted for drug resistance profiling in London. Within this dataset 26.9% of sequences were classified by STAR as non-B subtypes.

Background/objective: There is concern that use of highly active antiretroviral therapy (HAART) may be linked to increased sexual risk behaviour among homosexual men. We investigated sexual risk behaviour in HIV positive homosexual men and the relation between use of HAART and risk of HIV transmission., Methods: A cross sectional study of 420 HIV positive homosexual men attending a London outpatient clinic. Individual data were collected from computer assisted self interview, STI screening, and clinical and laboratory databases., Results: Among all men, sexual behaviour associated with a high risk of HIV transmission was commonly reported. The most frequently reported type of partnership was casual partners only, and 22% reported unprotected anal intercourse with one or more new partners in the past month. Analysis of crude data showed that men on HAART had fewer sexual partners (median 9 versus 20, p=0.28), less unprotected anal intercourse (for example, 36% versus 27% had insertive unprotected anal intercourse with a new partner in the past year, p=0.03) and fewer acute sexually transmitted infections (33% versus 19%, p=0.004 in the past 12 months) than men not on HAART. Self assessed health status was similar between the two groups: 72% on HAART and 75% not on HAART rated their health as very or fairly good, (p=0.55). In multivariate analysis, differences in sexual risk behaviour between men on HAART and men not on HAART were attenuated by adjustment for age, time since HIV infection. CD4 count and self assessed health status., Conclusion: HIV positive homosexual men attending a London outpatient clinic commonly reported sexual behaviour with a high risk of HIV transmission. However, behavioural and clinical risk factors for HIV transmission were consistently lower in men on HAART than men not on HAART. Although use of HAART by homosexual men with generally good health is not associated with higher risk behaviours, effective risk reduction interventions targeting known HIV positive homosexual men are still urgently needed.

Long-term effects of therapeutic vaccination of human immunodeficiency virus (HIV)-1-infected subjects with HIV-1 p17/p24:Ty virus-like particles (p24-VLP) on progression to AIDS, death, a CD4 cell count

Objectives: To describe the presentation, pathology, and outcome of biopsy proved renal disease in HIV infected patients at a central London HIV unit from 1992 to 1996., Methods: Retrospective review of a computerised database and case notes to identify patients with renal disease confirmed by antemortem percutaneous renal biopsy or necropsy., Results: 17 patients were identified, 13 had biopsy and four necropsy confirmed renal disease. Abnormalities included HIV associated nephropathy (HIVAN) in seven (41%) patients, membranous glomerulonephritis (GN) in four (23%), haemolytic uraemic syndrome (HUS) in two (12%), and interstitial nephritis, rhabdomyolysis, IgA nephropathy, and membranoproliferative GN in one patient each. Although renal disease was the first presentation of HIV disease in six (35%) patients the majority had advanced HIV disease (median CD4 count 40 x 10(6)/l). The commonest presentation was acute renal failure (ARF) in 10 (59%) patients, chronic renal failure (CRF) in five (29%), and proteinuria alone in two (12%). Although the majority of patients died during the study period (9/13) only three deaths were attributable to their renal disease. Survival ranged in those with HIVAN from 0 to 31 (median 10) months and, in those with membraneous GN from 1 to 46 (median 29) months., Conclusions: HIVAN was the commonest renal disease found in this group of patients; however, a variety of other pathologies were seen with variable outcomes. All cases of HIVAN were in patients of African or Afro-Caribbean origin and for the majority this was their first presentation of HIV disease. Nephrologists need to be aware of the possibility of HIV infection in patients presenting with renal disease.

Objectives: To compare the results of clinical assessment and MRI with neuropathological findings in the diagnosis of HIV and cytomegalovirus (CMV) associated CNS disease., Methods: A retrospective study of 35 patients infected with HIV who were examined at necropsy between four and 70 (median 20) days after neurological assessment and MRI., Results: Of the 35 patients, 19 had diffuse white matter hyperintensity on T2 weighted MRI, six of whom also had focal lesions. Nine other patients had focal white matter lesions and seven had changes in cortical atrophy only. Necropsy in the 19 with diffuse white matter hyperintensity showed HIV leukoencephalopathy (HIVLEP) with encephalitis in 10, CMV encephalitis in three, both HIVLEP/HIV encephalitis and CMV encephalitis in one, lymphoma in three, and non-specific inflammation in two. Necropsy in the 16 other patients without diffuse white matter hyperintensity showed CMV encephalitis in six, HIV encephalitis (without HIVLEP) in two, CMV encephalitis and HIVLEP/HIV encephalitis in one, non-HIV associated abnormalities in five, herpes simplex encephalitis in one, and lymphoma in one. CMV DNA was detected in CSF of five of seven patients with CMV encephalitis and in two of two with CMV associated polyradiculopathy but without CMV encephalitis. Diffuse white matter hyperintensity on MRI had a sensitivity of 100%, a specificity of 66.6%, and a positive predictive value of 58% for diagnosis of HIVLEP., Conclusion: Diffuse white matter hyperintensity on MRI can be due to either HIV or CMV associated pathology or non-specific abnormalities.

Objective: To determine whether proton magnetic resonance spectroscopy (MRS) demonstrates central nervous system abnormalities in asymptomatic HIV-1-infected individuals., Design: Both prospective and retrospective cross-sectional analyses of MRS in asymptomatic HIV-infected individuals., Setting: Two specialists HIV/AIDS outpatient facilities in London., Participants: Eighty-four HIV-1 seropositive asymptomatic men; 29 HIV-1 antibody-negative homosexual men at high-risk for HIV infection and 48 HIV-1 antibody-negative men at low-risk for HIV infection as controls., Main Outcome Measures: Single voxel, gradient-localized proton MRS performed at 1.5 T with 135 msec echo-time and 1,600 msec repeat-time in an 8 ml volume of interest positioned in the parieto-occipital white matter. Spectroscopic results were expressed as ratios between the areas under the N-acetyl (NA), creatine (Cr) and choline (Cho) resonance peaks., Results: There were no differences between those controls at high and those at low-risk for HIV infection. Comparing the combined control groups with the asymptomatic seropositive patients there were statistically significant differences in NA/Cho, NA/Cr (both P < 0.05) and NA/(NA + Cho + Cr) (P < 0.01)., Conclusion: Abnormalities in cerebral biochemistry may be demonstrated by proton MRS during asymptomatic HIV-1 infection.

A 210-bp DNA segment specific to the human herpesvirus 8 (HHV-8) genome was amplified by nested polymerase chain reaction from 10 of 14 archived oral biopsy samples of HIV-positive patients in London who had no evidence of oral Kaposi's sarcoma (KS). Various oral sites were represented. Oral tissues from 20 general dental patients not known to be HIV-infected were negative. When DNA sequences of these products were compared with sequences derived from 5 oral KS tissues of AIDS patients in London and 10 skin biopsies of Italian patients with Mediterranean KS (total number of positive tissues = 25), 11 were found to be unique. DNA and predicted peptide motifs of these sequences were also different from those in 28 of 36 HHV-8-positive lesions previously reported from American and African patients. HHV-8 is tropic for the oral mucosa of HIV-infected persons, and HHV-8 variants, though diverse, may be geographically restricted.

The purpose of this study was to examine by proton spectroscopy for any difference in cerebral metabolites in patients taking part in the Concorde study (comparing the efficacy of immediate versus deferred treatment with zidovudine on asymptomatic HIV infected individuals). Forty seven HIV positive male patients [29 immediate, 18 deferred zidovudine] were examined in the last 9 months of the therapeutic trial. Magnetic resonance imaging and proton spectroscopy were performed at 1.5 Tesla using a single voxel placed in the parieto-occipital white matter. No significant difference was found in metabolite ratios comparing immediate versus deferred zidovudine (NA/NA+Cho+Cr 0.52 vs. 0.52). High quality spectra were acquired in relatively large numbers of patients and logistically spectroscopy may be applied to clinical therapeutic studies.

In studies of the natural history of human immunodeficiency virus type 1 (HIV-1) infection, it has been repeatedly shown that higher-titer antibody responses to the HIV gag p24 protein correlate with less rapid disease progression. In HIV-negative persons, immunization with HIV-1 p17/p24:Ty virus-like particles (p24-VLP) induced humoral and cellular immune responses to p24. This construct was therefore studied as a potential immunotherapeutic agent with the objective of augmenting the immune response to p24 in a double-blind placebo-controlled trial involving 74 p24 antibody-positive, asymptomatic HIV-1-infected subjects with CD4 cell counts > 350/mm3. Immunization with p24-VLP was generally well tolerated. Immunization with p24-VLP did not increase p24 antibody levels and had no effect on CD4 cell counts or virus load. The failure to increase p24 antibody titers cannot entirely be explained by the subjects' immunodeficiency because most generated an antibody response to Ty, a yeast component of the immunogen.