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Biomedical subjects

S Jurriaans

Publications and source records attributed to S Jurriaans.

At least 37 records · Page 2Linked to original sources
PubMed1999

Immuno-activation with anti-CD3 and recombinant human IL-2 in HIV-1-infected patients on potent antiretroviral therapy.

BACKGROUND: A stable reservoir of latently infected, resting CD4 T cells has been demonstrated in HIV-1-infected patients despite prolonged antiretroviral treatment. This is a major barrier for the eradication of HIV by antiretroviral agents alone. Activation of these cells in the presence of antiretroviral therapy might be a strategy to increase the turnover rate of this reservoir. METHODS: Three HIV-1-positive patients on potent antiretroviral therapy, in whom plasma viremia had been suppressed to below 5 copies/ml for at least 26 weeks, were treated with a combination of OKT3 (days 1-5) and recombinant human IL-2 (days 2 6). RESULTS: The side-effects were fever, headache, nausea, diarrhea, and in one of the patients transient renal failure and seizures. The regimen resulted in profound T cell activation. In one patient plasma HIV-1 RNA transiently increased with a peak at 1500 copies/ml. In the other two patients plasma HIV-1 RNA levels remained below the detection limit, but HIV-1 RNA levels in the lymph nodes increased two- to threefold. All patients developed antibodies against OKT3. CONCLUSION: OKT3/IL-2 resulted in T cell activation and proliferation, and could stimulate HIV replication in patients having achieved prolonged suppression of plasma viremia. OKT3/IL-2 therapy was toxic and rapidly induced antibodies against OKT3.

Anti-HIV Agents↗
PubMed1999

[Primary HIV-infection: infectious mononucleosis-like presentation with treatment options].

Two patients, men aged 39 and 52 years, are described with a mononucleosis-like syndrome, due to a primary HIV infection. Both patient developed dermatological manifestations. One patient presented with an encephalitis with an inversed CD4/CD8 cell ratio in the cerebrospinal fluid. Primary HIV infection is often missed as a clinical diagnosis. The possible preservation of a strong cellular immune response against HIV itself in case of early start of treatment argues for an immediate intervention with a combination of antiretroviral drugs in this syndrome.

Acute Disease↗
PubMed1999

Evaluation of the World Health Organization staging system for HIV infection and disease in Ethiopia: association between clinical stages and laboratory markers.

OBJECTIVE: To study the association between the clinical axis of the World Health Organization (WHO) staging system of HIV infection and disease and laboratory markers in HIV-infected Ethiopians. DESIGN: Cross-sectional study. METHODS: Clinical manifestations and stage of HIV-positive individuals participating in a cohort study of HIV infection progression, and of HIV-positive patients hospitalized with suspicion of AIDS, were compared to CD4+ T-cell count and viral load. RESULTS: Of the 86 HIV-positive participants of the cohort study, 53 (62%), 16 (19%), 16 (19%), and one (1.2%) were in stage 1, 2, 3 and 4, respectively. Minor weight loss (n = 15) and pulmonary tuberculosis (n = 9) were the most commonly diagnosed conditions among the 38 (44%) symptomatic HIV-positive individuals. Although 23 (27%) HIV-positive participants had CD4+ T-cell counts less than 200 x 10(6)/l, only one was in clinical stage 4. Among 79 hospitalized HIV-positive patients, 15 (19%) and 64 (81%) were in stage 3 and 4, respectively. The majority (83.5%) had CD4+ T-cell counts < 200 x 10(6)/l. Individuals at stage 3 had lower CD4+ T-cell counts and higher viral loads when seen in hospital as compared to cohort participants (P = 0.06 and 0.008, respectively). When grouping the two study populations, the median CD4+ T-cell count decreased (337, 262, 225, 126, and 78 x 10(6)/l, P< 0.01), and the median viral load increased (4.08, 3.89, 4.47, 5.65, and 5.65 log10 copies/ml, P < 0.01), with increasing clinical stage of HIV infection (1, 2, 3 cohort, 3 hospital, and 4, respectively). Median CD4+ T-cell counts were remarkably low in HIV-negative participants (749 x 10(6)/l), and in HIV-positive participants at stage 1 and 2 (337 and 262 x 10(6)/l, respectively). CONCLUSIONS: There was a good correlation between WHO clinical stages and biological markers. CD4+ T-cell counts were low in Ethiopians, particularly during early stages of HIV-1 infection, and preliminary reference values at different stages of HIV-1 infection were determined. In HIV-infected Ethiopians, lymphocyte counts less than 1,000 x 10(6)/l in non-hospitalized individuals, and less than 2,000 x 10(6)/l in hospitalized patients, had high positive predictive value, but low sensitivity, in identifying subjects with low CD4+ T-cell counts (< 200 x 10(6)/l) who would benefit from chemoprophylaxis of opportunistic infections. The on-going longitudinal study will be useful to confirm the prognostic value of the WHO staging system.

Biomarkers↗
PubMed1999

Insertion of two amino acids combined with changes in reverse transcriptase containing tyrosine-215 of HIV-1 resistant to multiple nucleoside analogs.

OBJECTIVE: To identify genotypic drug resistance patterns of HIV-1 in patients who were extensively pretreated with anti-HIV drugs and not responding to their current antiretroviral combination therapy. METHODS: Drug susceptibility of the viruses was tested by a phenotypic recombinant virus assay. Genotypic analysis of HIV resistance was performed by sequencing of the amino-terminal part of the corresponding reverse transcriptase (RT) gene (amino acids 1-280) for serum-derived and recombinant viruses. RESULTS: Among viruses from 92 patients studied, three (3%) viruses contained a T215Y amino-acid change as well as a previously unseen combination of an amino-acid change at codon 67 (N-->E/S) and a two amino-acid insertion between codons 68 and 69 of the RT gene of HIV-1. Phenotypic resistance analysis showed high levels of resistance to zidovudine, lamivudine and stavudine (in all patients) and moderate levels of resistance to didanosine and zalcitabine (in two patients), whereas neither serum-derived nor recombinant viruses contained previously known amino-acid changes conferring resistance to didanosine, zalcitabine, lamivudine and stavudine. However, all recombinant viruses contained an insertion of two amino acids between codons 68 and 69 of RT as well as an amino-acid change at codon 67, as was seen in the serum-derived viruses. CONCLUSIONS: Antiretroviral therapy including zidovudine may yield replicating viruses with a two amino-acid insertion in RT in combination with amino-acid changes at codons 67 and 215, which are highly resistant to lamivudine and stavudine on top of zidovudine and have unpredictable susceptibility to didanosine and zalcitabine despite lack of previously reported corresponding resistance-associated amino-acid changes. It is currently unknown what regimens can induce the emergence of this type of multidrug-resistant viruses. This will only be elucidated when resistance assays are capable of detecting these mutants.

Adult↗
PubMed1999

Outcome and predictors of failure of highly active antiretroviral therapy: one-year follow-up of a cohort of human immunodeficiency virus type 1-infected persons.

The outcome and predictors of virologic treatment failure of highly active antiretroviral therapy (HAART) were determined for 271 human immunodeficiency virus (HIV)-infected protease inhibitor-naive persons. During a follow-up of 48 weeks after the initiation of HAART, 6.3% of patients experienced at least one new AIDS-defining event, and 3.0% died. Virologic treatment failure occurred in 40% (indinavir, 27%; ritonavir, 30%; saquinavir, 59%; ritonavir plus saquinavir, 32%; chi2, P=.001). Risk factors for treatment failure were baseline plasma HIV-1 RNA (odds ratio [OR], 1.70 per log10 copies increase in plasma HIV-1 RNA), baseline CD4 cell count (OR, 1. 35 per 100 CD4 cells/mm3 decrease), and use of saquinavir versus other protease inhibitors (OR, 3.21). During the first year of treatment, 53% of all patients changed (part of) their original HAART regimen at least once. This was significantly more frequent for regimens containing saquinavir (62%; 27% for virologic failure) or ritonavir (64%; 55% for intolerance) as single protease inhibitor.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Longitudinal phenotypic analysis of human immunodeficiency virus type 1-specific cytotoxic T lymphocytes: correlation with disease progression.

Few studies have examined longitudinal changes in human immunodeficiency virus type 1 (HIV)-specific cytotoxic T lymphocytes (CTL). To more closely define the natural history of HIV-specific CTL, we used HLA-peptide tetrameric complexes to study the longitudinal CD8(+) T-cell response evolution in 16 A*0201-positive untreated individuals followed clinically for up to 14 years. As early as 1 to 2 years after seroconversion, we found a significant association between high frequencies of A*0201-restricted p17(Gag/Pol) tetramer-binding cells and slower disease progression (P < 0.01). We observed that responses could remain stable over many months, but any longitudinal changes that occurred were typically accompanied by reciprocal changes in RNA viral load. Phenotypic analysis with markers CD45RO, CD45RA, and CD27 identified distinct subsets of antigen-specific cells and the preferential loss of CD27(+) CD45RO(+) cells during periods of rapid decline in the frequency of tetramer-binding cells. In addition we were unable to confirm previous studies showing a consistent selective loss of HIV-specific cells in the context of sustained Epstein-Barr virus-specific cell frequencies. Overall, these data support a role of HIV-specific CTL in the control of disease progression and suggest that the ultimate loss of such CTL may be preferentially from the CD27(+) CD45RO(+) subset.

Disease Progression↗
PubMed1998

An open randomized controlled trial of zidovudine plus lamivudine versus stavudine plus lamivudine.

OBJECTIVE: To compare the antiretroviral effect and safety of zidovudine (ZDV)-lamivudine (3TC) with that of stavudine (d4T)-3TC. METHODS: In an open randomized controlled trial antiretroviral therapy-naive patients who had CD4+ counts > or = 200 x 10(6)/l and plasma HIV RNA load > or = 10000 copies/ml were randomized to receive ZDV-3TC (200 mg three times daily and 150 mg twice daily, respectively) or d4T-3TC (40 mg and 150 mg, both twice daily). If the plasma HIV RNA level at week 8 or thereafter was > 500 copes/ml, indinavir was added at the next scheduled visit. Genotypic resistance analysis of the reverse transcriptase gene was performed at week 0 and 12. Results over 24 weeks were reported. RESULTS: Forty-seven patients were treated (24 took ZDV-3TC; 23 took d4T-3TC). Plasma HIV RNA levels decreased from median 4.80 to 3.15 log10 copies/ml (ZDV-3TC, P < 0.0001) and from 4.98 to 3.03 log10 copies/ml (d4T-3TC, P < 0.0001) after 12 weeks of treatment. Indinavir was added at week 12 in 11 out of 21 patients with ZDV-3TC and in 10 out of 22 patients with d4T-3TC. Median virus load at week 24 was 2.41 log10 and 2.29 log10 copies/ml (P=0.14), respectively. Seventy-five per cent (15 out of 20; ZDV-3TC) and 95% (18 out of 19; d4T-3TC) of patients had a virus load of < 500 copies/ml. Genomic evidence for 3TC resistance was found in all patients tested (11/11 ZDV-3TC and 12/12 d4T-3TC). At week 12, CD4 cell counts had increased with a median of 110 x 10(6)/l in the ZDV-3TC group (baseline, 315 x 10(6)/l) and a median of 115 x 10(6)/l in the d4T-3TC group (baseline 290 x 10(6)/l). At week 24, the median increases were 90 and 120 x 10(6)/l, respectively. Overall the increase of CD4+ cells was higher in the d4T-3TC group (P=0.02). CONCLUSION: d4T-3TC is at least as effective as ZDV-3TC, but 3TC resistance emerged in all patients investigated. The virological response of the dual nucleoside combination is of short duration. However, after addition of indinavir the virus load could be reduced to < 500 copies/ml in the majority of patients. The increase in CD4+ cell count was significantly greater in the d4T-3TC group. To prevent 3TC resistance, the drug should not be used in regimens containing only two nucleosides, irrespective the virus load at baseline.

Adult↗
PubMed1998

The effect of plasma drug concentrations on HIV-1 clearance rate during quadruple drug therapy.

OBJECTIVE: To investigate the relationship between exposure to antiretroviral drugs and the initial decline of plasma HIV-1 RNA. DESIGN: Open-label study in antiretroviral-naive HIV-1 infected patients using a quadruple drug regimen [nelfinavir (NFV), saquinavir (SQV), stavudine, and lamivudine]. METHODS: The elimination rate constant (k) for HIV-1 clearance was calculated during the first 2 weeks of treatment in 29 patients. Exposure to NFV and SQV was quantified on each study visit. Observed NFV and SQV concentrations were related to those expected in a reference population and a concentration ratio was calculated. The median concentration ratios for NFV and SQV, the baseline CD4+ lymphocyte count and baseline log10 HIV-1 RNA were correlated with k. RESULTS: A significant positive correlation was observed between k and the median NFV (P = 0.001) or SQV concentration ratio (P = 0.016) in univariate analysis. In multivariate analyses, the median NFV concentration ratio remained significantly correlated with k. CONCLUSIONS: The variation in the rate of decline of plasma HIV-1 RNA between patients after the initiation of a quadruple drug regimen could be explained by differences in exposure to NFV or SQV. Determination of k could be used to optimise further antiretroviral drug therapy and may be a first tool to assess antiretroviral activities of new or increasing doses of drugs administered in combination regimens. Furthermore, our data suggest that exposure to antiretroviral drugs should be incorporated in mathematical models to describe HIV-1 dynamics in more detail.

Anti-HIV Agents↗
PubMed1998

Alternative multidrug regimen provides improved suppression of HIV-1 replication over triple therapy.

OBJECTIVE: To compare the viral suppression of two antiretroviral regimens using three drugs or five drugs. DESIGN: Two open-label studies using a three-drug (zidovudine, lamivudine and ritonavir) and a five-drug regimen (zidovudine, lamivudine, abacavir, indinavir and nevirapine) in study-drug-naive patients, except for one in the five-drug study. METHODS: Participants with > or = 10 000 HIV-1 RNA copies/ml in plasma at baseline were compared by means of Kaplan-Meier curves for time to < 50 copies/ml, as well as linear regression analysis for the first phase of decline using log-transformed copy numbers. RESULTS: The elimination rate constants for HIV-1 RNA in 15 participants of the three-drug study were compared with nine participants of the five-drug study. The level of < 50 copies/ml was reached earlier when using the five-drug than when using the three-drug regimen (P log rank = 0.0005): median time to reach this level was 4 weeks and 12 weeks, respectively. No differences were found in HIV-1 RNA elimination rate constants in the first 2 weeks after the initiation of therapy. When the viral load declines were calculated from day 2 onwards, adjusting for differences in pharmacological delay of the drugs used, again no differences in early viral load decline were found between the two regimens. CONCLUSION: With the five drugs used in this study, the median time to reach < 50 HIV-1 RNA copies/ml was 8 weeks shorter than with the three-drug regimen. This finding shows that suppression of viral load in HIV-infection by standard triple-drug therapy can be improved upon.

Adult↗
PubMed1998

Maintenance therapy after quadruple induction therapy in HIV-1 infected individuals: Amsterdam Duration of Antiretroviral Medication (ADAM) study.

BACKGROUND: Highly active antiretroviral therapy (HAART) has led to health benefits for patients infected with HIV-1. However, long-term use of multidrug regimens is difficult to sustain. Simplifying antiretroviral treatment regimens would increase patients' adherence and minimise toxicity. We investigated the feasibility of a strategy of induction therapy followed by maintenance therapy with HAART in a randomised open-label study. METHODS: From March, 1997, we enrolled patients infected with HIV-1 with at least 200 CD4 cells/microL, at least 1000 HIV-1 RNA copies/mL in plasma, and no previous exposure to antiretroviral drugs. After 26 weeks of induction therapy (stavudine, lamivudine, saquinavir, and nelfinavir) patients were randomly allocated maintenance therapy (either stavudine and nelfinavir or saquinivir and nelfinavir) or prolonged induction therapy (if the plasma HIV-1 RNA concentration at weeks 24 and 25 was <50 copies/mL). FINDINGS: In February, 1998, we discontinued randomisation after an interim analysis. 62 patients had been enrolled. 39 (91%) of the 43 patients who were followed up for at least 26 weeks had an undetectable plasma HIV-1 RNA concentration at week 16. At week 26, 31 patients were randomly allocated treatment. Of these patients 25 had a total follow-up of at least 36 weeks. At week 36, a higher proportion of patients on maintenance therapy (nine [64%] of 14) had a detectable HIV-1 RNA than patients on prolonged induction therapy (one [9%] of 11, p=0.01). The initial virion-clearance rate during induction therapy was higher in five patients on maintenance therapy with a sustained undetectable plasma HIV-1 RNA concentration than in nine patients with recurrence of a detectable plasma HIV-1 RNA concentration at week 36 (0.35 vs 0.19 per day, respectively; p=0.0008). INTERPRETATION: The induction regimen provided a rapid suppression of viral replication to below 50 copies/mL. However, suppression was not sustained in a considerable number of patients who went onto maintenance therapy. It is currently inadvisable to continue attempts at moving from induction to maintenance therapy in day-to-day practice.

Adult↗
PubMed1998

Decrease of HIV-1 RNA levels in lymphoid tissue and peripheral blood during treatment with ritonavir, lamivudine and zidovudine. Ritonavir/3TC/ZDV Study Group.

OBJECTIVES: Triple combination treatment of HIV-1 infection using two reverse transcriptase inhibitors and a protease inhibitor can result in significant and sustained decreases in the quantity of viral RNA in peripheral blood. Lymphoid tissue, however, constitutes the major reservoir of HIV in infected patients. Study of the viral burden in these tissues has provided additional insight in the efficacy of antiretroviral treatment. DESIGN: Patients were randomized into two groups in order to study differences in the development of resistance to reverse transcriptase inhibitors. Group I started treatment with all three drugs simultaneously. Group II started with ritonavir monotherapy, aiming at initial reduction in virus production before the addition of lamivudine and zidovudine 3 weeks later. METHODS: Changes in the amount of HIV in plasma and tonsillar lymphoid tissue during 24 weeks of treatment with ritonavir, lamivudine and zidovudine were studied by reverse transcriptase polymerase chain reaction. RESULTS: Thirty-three antiretroviral-naive HIV-infected patients were included for analysis. After 24 weeks, median CD4+ cell count increased by 152 x 10(6)/l and median plasma viral RNA levels decreased by at least 2.87 log10 copies/ml. In 88% of the patients remaining on treatment, plasma RNA levels were below the quantification limit of the assay used (mean, 2.4 log10 copies/ml). The lymphoid tissue viral burden, ranging from 9.16 to 8.52 log10 copies/g at baseline, was markedly reduced with at least 2.1 log10 copies/g by week 24 in the five patients analysed. Eight patients (24%) withdrew because of side-effects. In one patient in group II, ritonavir and lamivudine resistance-associated mutations developed. CONCLUSIONS: Treatment with this triple antiretroviral drug combination produced a durable and strong decrease of HIV-1 RNA burden in both plasma and lymphoid tissue.

Adult↗
PubMed1998

In vivo delayed-type hypersensitivity skin test anergy in human immunodeficiency virus type 1 infection is associated with T cell nonresponsiveness in vitro.

In a cross-sectional study, the prevalence of delayed-type hypersensitivity skin test anergy (DTHA) was examined in 136 asymptomatic human immunodeficiency virus-infected participants in relation to immunologic and virologic parameters. DTHA was assessed with a multitest cell-mediated immunity skin test. Of the 136 participants, with a mean CD4 T cell count of 335 x 10(6)/L, 25 were anergic (18.4%). In the stepwise forward multivariate logistic regression models, after adjustment for CD4 T cell counts, depending on whether it was analyzed continuously or after dichotomization (20th percentile), both T cell reactivity to CD2 plus CD28 antibodies or to CD3 antibodies were the most predictive markers of DTHA (odds ratio, 0.80; 95% confidence interval, 0.67-0.94; and odds ratio, 2.97; 95% confidence interval, 1.1-8.3, respectively). This study shows a strong correlation between the decreased T cell responses in vitro and DTHA. Therefore, next to DTHA testing, T cell function assays may be useful to test immune reconstitution observed during antiretroviral treatment.

Adult↗
PubMed1997

[Zidovudine-resistant HIV strains in untreated intravenous drug users and homosexual men in Amsterdam infected in 1996].

OBJECTIVE: To gain insight into the spread of HIV strains with different sensitivities to antiretroviral drugs prescribed in the Netherlands. DESIGN: Prospective cohort study in intravenous drug users and homosexual men. SETTING: Amsterdam, the Netherlands. METHODS: HIV negative participants in the Amsterdam cohort studies among homosexual men and intravenous drug users are tested two to three times a year for HIV antibodies. The first positive serum sample of those who seroconverted was used to determine, on the basis of the nucleotide sequence of the reverse transcriptase gene of HIV, if viruses were present with a reduced sensitivity to reverse transcriptase inhibitors. RESULTS: In 1996, 17 new HIV infections occurred (8 in homosexual men and 9 in intravenous drug users). In two new infections in homosexual men HIV strains with reduced sensitivity to zidovudine were present.

Anti-HIV Agents↗
PubMed1996

Fluctuations in steady state level of genomic HIV-1 RNA and replication intermediates related to disease progression rate.

Steady state levels of HIV-1 genomic RNA and unintegrated circular DNA fluctuate in the course of HIV-1 infection. Genomic RNA in serum was detected using the NASBA technique and the amount of circular DNA was assessed by PCR. Quantification was done by competitive techniques using co-amplification of internal standards. Within the Amsterdam Cohort Studies it was possible to distinguish rapid progressors, intermediate progressors, slow progressors and non-progressors. Rapid progressors show persistently high viral RNA loads from seroconversion on, while all other HIV-1-infected individuals show a steady decline after seroconversion. Subsequent rises in viral RNA levels herald disease progression in later stages of infection. Unintegrated circular DNA shows similar, but somewhat delayed kinetics. These results indicate that the distribution of AIDS and the average length of the symptom-free period in an HIV-1-infected host population is determined by the steady state levels of genomic RNA and of replication intermediates that are produced by a particular HIV-1 virus population in the average seropositive individual.

Biomarkers↗
PubMed1995

Increased number of single-LTR HIV-1 DNA junctions correlates with HIV-1 antigen expression and CD4+ cell decline in vivo.

Human immunodeficiency type 1 (HIV-1) DNA in peripheral blood cells of HIV-1 infected individuals may be present as integrated and/or unintegrated DNA. Several reports have indicated that a major proportion of HIV-1 DNA in the asymptomatic phase is linear, full-length, and unintegrated and in the symptomatic phase either circular unintegrated or integrated in the host genome. We developed a quantitative polymerase chain reaction (PCR) technique to detect single-LTR HIV-1 DNA junctions, reflecting the presence of unintegrated single-LTR circles. In vitro infection of a CD4+ T-cell line resulted first in the increase of single-LTR junctions followed by syncytium formation and a rise of p24 antigen production. The number of single-LTR HIV-1 DNA junctions was further studied in two acutely infected individuals and in 21 long-term infected individuals. The number of single-LTR junctions was significantly correlated with CD4+ cell decline, p24 antigen expression, and total HIV-1 DNA content of peripheral blood mononuclear cells (PBMC). Single-LTR HIV-1 DNA junctions were absent from PBMC containing other forms of HIV-1 DNA in four of nine non/slow progressors relative to 2 of 12 rapid progressors/AIDS patients. We conclude from our data that quantitative detection of single-LTR HIV-1 DNA junctions can be used as an early DNA marker of the transition from clinical latency to active replication in the peripheral blood.

Base Sequence↗
PubMed1995

Distinct changes in HIV type 1 RNA versus p24 antigen levels in serum during short-term zidovudine therapy in asymptomatic individuals with and without progression to AIDS.

Serum HIV-1 RNA and p24 antigen levels were examined in 28 seropositive asymptomatic individuals participating in a trial on the efficacy of zidovudine. Sixteen individuals remained asymptomatic until 4 years after the onset of the trial, whereas 12 individuals were diagnosed with an AIDS-defining event. The serum HIV-1 RNA load and p24 antigen levels were determined before the onset of therapy and during the first 8 weeks of therapy to establish whether the patterns of change were predictive of clinical outcome. Among the 28 participants 43% had measurable pretreatment concentrations of p24 antigen. Initiation of zidovudine therapy was followed by a similar decline of p24 antigen levels in nonprogressors as well as progressors and, therefore, these groups could not be distinguished on the basis of this parameter. HIV-1 RNA was detected in the pretreatment samples of 82% of the individuals and could be detected in p24 antigen-positive as well as p24 antigen-negative individuals. Similar changes in HIV-1 RNA load during zidovudine therapy were observed in p24 antigen-positive and -negative individuals. Analysis of the HIV-1 RNA response according to clinical outcome demonstrated that HIV-1 RNA copy numbers had declined significantly after 4 weeks of therapy in both nonprogressors and progressors, but the decline in RNA load was much stronger in the nonprogressors. Our data show that the HIV-1 RNA load in serum can be used to monitor the response to antiviral therapy in p24 antigen-positive as well as -negative individuals. Posttreatment changes in p24 antigen levels are not indicative for clinical outcome, whereas RNA copy numbers are.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1995

Predictors for non- and slow progression in human immunodeficiency virus (HIV) type 1 infection: low viral RNA copy numbers in serum and maintenance of high HIV-1 p24-specific but not V3-specific antibody levels.

To gain insight into determinants that define the duration of the asymptomatic period preceding AIDS, groups of long-term asymptomatic (LTA) person (> 7 years of follow-up) and slow and rapid progressors of human immunodeficiency virus infection were studied. LTAs had no clinical manifestations of AIDS or immunologic abnormalities in 7 years of follow-up. RNA copy numbers, gag- and env-specific, and neutralizing antibody titers in serum were determined 1 and 5 years after seroconversion or entry into the cohort. Early in infection, before immunologic markers or clinical manifestations allowed group discrimination, subjects who were later classified as LTAs had significantly less serum viral RNA than progressors. No significant increase in virus load was found in progressors, indicating that the initial load defines clinical outcome. In slow progressors, high virus load was associated with high p24-specific antibody titers, suggesting that delay of clinical manifestations of AIDS may be related to the presence of high levels of p24-specific but not V3-specific antibodies.

Acquired Immunodeficiency Syndrome↗