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Biomedical subjects

Alessandro Cozzi-Lepri

Publications and source records attributed to Alessandro Cozzi-Lepri.

At least 19 recordsLinked to original sources
PubMed2006

A comparison between abacavir and efavirenz as the third drug used in combination with a background therapy regimen of 2 nucleoside reverse-transcriptase inhibitors in patients with initially suppressed viral loads.

BACKGROUND: Our objective was to compare the rate of viral rebound and therapy failure in patients receiving abacavir or efavirenz as the third drug (in addition to 2 non-abacavir nucleosides) in combination antiretroviral therapy (cART) and to compare the rate of metabolic alteration associated with these regimens. METHODS: We conducted a multicohort prospective observational study of human immunodeficiency virus-infected patients who had attained viral loads < or = 80 copies/mL while receiving cART, without having previously received antiretrovirals. The rates of virological rebound, therapy failure, and lipid-level alteration during follow-up were calculated as the number of events divided by person-years of follow-up (PYFU). A multivariable analysis was performed using a Poisson regression model. RESULTS: We studied a total of 744 patients; the median age was 37 years, 27% of the patients were female, and 41% were heterosexual. There was a total of 854 PYFU spent receiving efavirenz and 285 spent receiving abacavir. The nucleoside reverse-transcriptase inhibitor pairs most frequently used were zidovudine/lamivudine (66% of PYFU), stavudine/lamivudine (17.6%), and stavudine/didanosine (5.4%). The adjusted relative rates of virological failure and therapy failure for abacavir, compared with those for efavirenz, were 2.17 (95% confidence interval [CI], 1.12-4.18; P = .02) and 1.41 (95% CI, 1.01-2.01; P = .05), respectively. CONCLUSIONS: Patients with virological suppression while receiving regimens containing abacavir appear more likely to experience virological and therapy failure than those receiving efavirenz as their third drug. Although this is a selected group of adherent patients, bias cannot be ruled out, because this is a nonrandomized comparison.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Significant link between sCD30 changes and HIV viremia in patients treated with HAART.

Elevated sCD30 levels were generally associated with poor prognosis in chronic HIV infection prior to the era of highly active antiretroviral therapy (HAART). Little information is available on sCD30 and HIV-1 viremia. In this study, the association between sCD30 and HIV-1 viremia was investigated in HIV-infected patients who underwent HAART. sCD30 was measured in 276 patients prior (T0) and 6 months after HAART (T6). Standard survival analyses were used to evaluate the prognostic value of sCD30 and sCD30 change from baseline to predict the virological response to HAART. Higher levels (>30 U/ml) of sCD30 prior to HAART were associated with relatively higher viremia (P = 0.0001) and tended to be associated with a lower chance of achieving virological success (P = 0.13). The median T6 sCD30 level in patients who concomitantly had viremia >500 copies/ml was higher than the median sCD30 level of those with viremia </=500 copies/ml (P = 0.002). Conversely, within the patients who achieved viral suppression on HAART, those who had concomitantly a larger reduction in sCD30 subsequently experienced a higher rate of virological failure (P = 0.04). A strong, but complex, link exists between sCD30 levels and HIV viremia in the era of HAART. The change in sCD30 levels from pre-therapy to the date of first viral suppression could be used to identify patients who are more likely to experience later virological rebound among those who achieve initially virological success.

Adult↗
PubMed2006

Impact of lamivudine on the risk of liver-related death in 2,041 HBsAg- and HIV-positive individuals: results from an inter-cohort analysis.

BACKGROUND: The impact of lamivudine (3TC) as part of combination antiretroviral therapy (cART) on the risk of liver-related death (LRD) in HIV/hepatitis B virus (HBV)-coinfected patients has not been extensively studied. METHODS: We performed an analysis involving HIV/HBV-coinfected patients in 13 cohorts who initiated cART. The end-point was LRD--that is, death with concomitant decompensated liver disease (DLD) or hepatocellular carcinoma--as the main cause. Incidence rates of LRD after initiation of cART were expressed as number of events per 100 person-years of follow-up (PYFU). A Poisson regression model adjusted for cohort, gender, mode of HIV transmission, CD4+ T-cell count at cART initiation, liver disease pre-cART, duration of 3TC before cART, and hepatitis C virus was used to assess the association between use of 3TC and risk of LRD. RESULTS: We analysed 2,041 patients. Follow-up after starting cART was 7,648 PYFU (5,569 spent on 3TC-containing regimens) with a median per person of 48 months (range: 2-91). Of the total, 217 subjects died; 57 deaths were liver-related resulting in a rate of 7.5 per 1,000 PYFU [95% confidence intervals (CI): 5.6-9.7]. The relative risk of LRD per extra year of 3TC use was 0.73 (95% CI: 0.59-0.90, P = 0.004). CONCLUSION: The use of 3TC was associated with a reduced risk of LRD over 4 years of follow-up. This study supports the current view that the use of 3TC as part of cART should be considered in patients who are tested positive for HBsAg.

Adult↗
PubMed2006

Evolution of HVR-1 quasispecies after 1-year treatment in HIV/HCV-coinfected patients according to the pattern of response to highly active antiretroviral therapy.

Hepatitis C virus (HCV) variability is mainly attributed to the ability of the virus to respond to host immune pressure, acting as a driving force for the evolution of quasispecies. This study was aimed at studying the changes in HVR-1 heterogeneity and the evolution of HCV quasispecies in HIV/HCV-coinfected patients according to the pattern of response to highly active antiretroviral therapy (HAART). Sixteen HIV/HCV-coinfected patients harbouring HCV genotype 1 and who had been on HAART for at least 1 year, 8 showing increasing CD4+ T-cell counts (immunological responders) and 8 showing a stable or decreasing CD4+ T-cell counts (immunological nonresponders), were selected from a prospective cohort study. After 1 year of HAART, 11 patients showed HIV viral load <2.6 log10 cp/ml (virological responders), and 5 showed HIV viral load above this value (virological non-responders). Plasma samples, collected before starting therapy and after 1 year of HAART, underwent clonal sequence analysis for HVR-1 region of HCV. Nonsynonymous/synonymous substitutions ratio (Ka/Ks), aminoacidic complexity (normalized Shannon entropy) and diversity (p-distance), were considered as parameters of quasispecies heterogeneity. After 1 year of HAART, heterogeneity of HVR-1 quasispecies significantly decreased in virological non-responders, whereas the heterogeneity tended to increase in virological responders. The differences in the evolution were less stringent, when considering immunological response. On the other hand, profound qualitative modifications of HVR-1 quasispecies were observed only in patients with both immunological and virological HAART response. On the whole, these findings suggest that, in patients undergoing HAART, the extent of HCV variability and the evolution of HVR-1 quasispecies is influenced by the pattern of response to antiretroviral therapy.

Adult↗
PubMed2006

Lopinavir/ritonavir or efavirenz plus two nucleoside analogues as first-line antiretroviral therapy: a non-randomized comparison.

BACKGROUND: Although efavirenz (EFV) and lopinavir/ ritonavir (LPV/r) are both recommended antiretroviral agents for combination therapy in drug-naive HIV-infected patients, no randomized comparison of their efficacy and tolerability is available yet. A multi-cohort prospective observational comparative study was performed. METHODS: Efficacy was examined comparing time to virological failure, CD4 recovery and clinical progression. Tolerability was examined comparing time to treatment discontinuation for any reason and for toxicity and time to liver enzymes or lipid alterations. Survival analysis was conducted by an intent-to-treat principle using the Kaplan-Meier method, and standard and weighted Cox regression models. RESULTS: A total of 674 antiretroviral-naive patients starting a two nucleoside reverse transcriptase inhibitor regimen plus either EFV (n = 481) or LPV/r (n = 193) were examined. At baseline, patients starting LPV/r had higher HIV RNA and lower CD4+ T-cell counts. There was no difference in the adjusted hazards of virological failure (LPV/r versus EFV relative hazard [RH] 1.16, 95% confidence intervals [CI]: 0.58-2.32, P = 0.67), CD4 recovery (RH = 0.93, 95% CI: 0.66-1.30, P = 0.66), clinical progression (RH = 1.64, 95% CI: 0.70-3.84, P = 0.25), drug discontinuation for toxicity (RH = 0.92, 95% CI: 0.51-1.64, P = 0.76) and for any reason, and rates of liver enzyme and total/low density lipoprotein (LDL) cholesterol elevation. In contrast, the rate of triglycerides elevations (> 1 NCEP Adult Treatment Panel III category increase) was higher in the LPV/r group (RH = 1.69, 95% CI: 1.14-2.50; P = 0.01). Models weighted for the inverse of conditional probability of receiving either drug applied to the efficacy endpoints yielded similar results. CD4 recovery with both drugs was also similar in the lowest CD4 strata. CONCLUSIONS: Our analysis suggests similar efficacy and tolerability for EFV- or LPV/r-based first-line antiretroviral regimens. LPV/r was associated with higher rates of hypertriglyceridaemia.

Adult↗
PubMed2005

Multiple viral infections.

Individuals at risk of HIV are concomitantly at risk of acquiring parenterally or sexually transmitted viruses. Multiple hepatitis co-infection (HBV+HCV; HBV+HDV; HBV+HDV+HCV) has not been systematically sought after in the large cohorts of HIV-infected patients, but has been reported in 0.4% to more than 50% of patients. HIV-infected patients with multiple hepatitis have a higher rate of liver-related morbidity and mortality than patients with HIV infection alone or with a single hepatitis co-infection. The degree of immunodepression is an important factor in liver disease progression. Since GBV-C virus is transmitted parenterally or by sexual contact, a high prevalence was found in chronic hepatitis C and in HIV-infected patients. Patients with multiple hepatitis have been excluded from randomised therapeutic trials of viral hepatitis in HIV-infected and HIV-negative patients. Thus, the therapeutic approach is based on the results of a small series and empirically oriented toward the prevailing infection. HIV-infected patients should be tested for hepatitis B, C and D systematically and hepatitis B vaccination should be considered for those with HCV co-infection and absence of HBV markers. Studies are needed to assess treatment strategies.

Global Health↗
PubMed2005

Role of hepatitis C virus (HCV) viremia and HCV genotype in the immune recovery from highly active antiretroviral therapy in a cohort of antiretroviral-naive HIV-infected individuals.

BACKGROUND: The roles of hepatitis C virus (HCV) viremia and HCV genotype in the immune response to highly active antiretroviral therapy (HAART) are poorly understood. Our aim was to assess the CD4+ cell count recovery after HAART in human immunodeficiency virus (HIV)-infected patients with HCV viremia and HIV-infected patients who tested negative for HCV antibody (HCV-Ab). We also aimed to assess whether the response to HAART in these patients varied according to HCV genotype. METHODS: The analysis focused on 1219 HCV-Ab-negative patients and 284 HCV-viremic patients from a cohort of HIV-infected subjects that includes persons who were antiretroviral naive before initiating HAART after cohort enrollment. HCV RNA load and HCV genotype were determined in plasma specimens obtained and stored during the 6-month period preceding the initiation of HAART. RESULTS: The chance of achieving a CD4+ cell count increase of > or = 100 cells/microL from the pre-HAART level tended to be poorer in HCV-viremic patients than in patients who tested negative for HCV-Ab (adjusted relative hazard [RH], 0.82; 95% confidence interval [CI], 0.66-1.01; P = .06). In contrast, a comparison of patients who had a HCV RNA load >1 x 10(6) IU/mL with patients who had a HCV RNA load of 5-1 x 10(6) IU/mL revealed no significant association between HCV RNA load and achievement of an increased CD4+ cell count (adjusted RH, 0.97; 95% CI, 0.75-1.27; P = .83). There was no clear association between HCV genotype and the probability of achieving a CD4+ cell count increase. CONCLUSIONS: An association between the presence of HCV-Ab and immune reconstitution after HAART has been shown elsewhere. Results of our large, prospective study support a direct role of HCV viremia in the CD4+ cell count response to HAART. Moreover, our results underline the fact that, in individuals coinfected with HIV and HCV, the goal of treating HCV infection is to eradicate HCV, to both slow the rate of HCV progression and limit potential interference with the response to HAART.

Adolescent↗
PubMed2005

Interruption of highly active antiretroviral therapy in HIV clinical practice: results from the Italian Cohort of Antiretroviral-Naive Patients.

OBJECTIVES: To investigate the frequency of a first therapy interruption (TI) > or = 12 weeks, to identify the factors associated with TI and with therapy resumption, and to compare the risk of developing clinical events during TI and during continuous therapy. METHODS: Observational study of 3142 patients who started a first highly active antiretroviral therapy (HAART) regimen. End points were time to (1) first TI of > or = 12 weeks, (2) subsequent therapy resumption, and (3) development of new AIDS-related events or death. RESULTS: Over a median follow-up period of 41 months (interquartile range: 18-60 months), 721 patients (22.9%) interrupted HAART for > or = 12 weeks, with a probability of 28.6% (95% confidence interval [CI]: 26.7-30.6) by 4 years from the date of therapy initiation. Patient decision (47.4%) and toxicity (24.0%) were the main reasons for TI. Women, injection drug users, and patients with a higher current CD4 cell count were more likely to interrupt. The median time to therapy resumption was 12 months (95% CI: 11-14). The higher the current CD4 count, the slower was the rate of resuming therapy; conversely, patients who stopped because of failure and those with a pre-HAART viral load >100,000 copies/mL resumed therapy sooner. Two hundred eighty-one patients experienced clinical progression at a rate of 2.6 per 100 person-years (pys) (95% CI: 2.3-3.0) while patients were on therapy and 3.5 per 100 pys (95% CI: 2.4-4.8) during TI. The adjusted relative hazard of clinical progression associated with TI was 2.75 (95% CI: 1.14-6.65; P = 0.03). CONCLUSIONS: TI occurring in clinical practice is associated with an increased risk of clinical progression; hence, it should be discouraged outside strictly experimental settings.

Adult↗
PubMed2005

CD4 cell-monitored treatment interruption in patients with a CD4 cell count > 500 x 106 cells/l.

BACKGROUND: Little is known about CD4 cell count changes in patients with high CD4 cell counts who interrupt antiretroviral therapy, especially in those with a nadir of 250-350 x 10 cells/l. METHODS: Data derived from 139 patients from seven prospective cohorts who had > 12 months highly active antiretroviral therapy (HAART), CD4 cell count nadir of > 250 x 10 cells/l and at pre-interruption of > 500 x 10 cells/l. Endpoint was time to CD4 cell count < 350 x 10 cells/l or reinitiation of treatment. RESULTS: At interruption, the median CD4 cell count was 800 x 10 cells/l, median viral load was 1.7 log10 copies/ml. At the time of analysis, 63 (45.3%) had resumed therapy or experienced < 350 x 10 cells/l CD4 cells over a median interruption of 75 weeks. Of these, 33 (52.4%) experienced a decline to < 350 x 10 cells/l and 30 (47.6%) restarted therapy before their CD4 cell count had fallen below this level. In 43 patients with CD4 cell nadir of 251-350 x 10 cells/l, median time to therapy resumption or CD4 cell count < 350 x 10 cells/l was 61 weeks. Higher CD4 cell count nadir, longer duration of viral load suppression on therapy, and higher viral load level at interruption were independently associated with longer time to restart therapy. The risk of clinical events was 5 per 1000 person-years of follow-up. CONCLUSIONS: Patients who started therapy with CD4 cell count of 250-350 x 10 cells/l and who later interrupted therapy appear able to remain off therapy with a CD4 cell count > 350 x 10 cells/l for a substantial period of time.

Adult↗
PubMed2005

Response to HAART and GB virus type C coinfection in a cohort of antiretroviral-naive HIV-infected individuals.

The prognostic role of GB virus type C (GBV-C) viraemia in HIV-infected subjects treated with highly active antiretroviral therapy (HAART) is still undefined. The aim of this analysis is to assess the relationship between GBV-C infection and response to antiretroviral therapy among HIV-infected subjects initiating HAART when antiretroviral-naive. A prospective, observational study of 400 HIV-infected patients with measurements of GBV-C RNA, hepatitis C virus (HCV) antibodies and HCV RNA determined from plasma stored prior to HAART initiation. Time to virological (achieving HIV RNA < or =500 copies/ml) and immunological success (a CD4+ count increase of > or =200 cells/microl), and the time to virological relapse (confirmed HIV RNA >500 copies/ml) were assessed by Kaplan-Meier methods and Cox proportional hazard regression model. Of the subjects, 117 (29.3%) were GBV-C positive and, overall, 351 (87.8%) patients achieved virological success. After controlling for a number of confounders including HCV RNA, GBV-C viraemic patients experienced a significantly lower risk of HIV rebound than those who were GBV-C negative [relative hazard (RH)=0.56, 95% CI: 0.34-0.93, P=0.03]. Conversely, the probability of achieving initial virological success or CD4+ count response after HAART did not differ between GBV-C-negative and -positive subjects. These results suggest that GBV-C coinfection may play a role in determining the rate of HIV rebound possibly by competing with HIV replication after HIV load has been successfully suppressed by HAART.

Adult↗
PubMed2005

Thymidine analogue mutation profiles: factors associated with acquiring specific profiles and their impact on the virological response to therapy.

BACKGROUND: Studies have suggested that HIV-1 may develop thymidine analogue mutations (TAMs) by one of two distinct pathways - the TAM1 pathway (including mutations 41L, 210W and 215Y) or the TAM2 pathway (including mutations 67N, 70R and 219E/Q) - under the pressure of a not fully suppressive thymidine-analogue-containing regimen. METHODS: Frozen plasma samples stored in the EuroSIDA repository were selected and sent to two central laboratories for genotypic analysis. We considered 733 patients with at least one genotypic test showing > or =1 TAMs (the first of these tests in chronological order was used). TAM1 and TAM2 genotypic profiles were defined in accordance with previous literature. Statistical modelling involved logistic regression and linear regression analysis for censored data. RESULTS: The observed frequencies of patterns classifiable as TAM1 or TAM2 profiles were markedly higher than the probabilities of falling into these classifications by chance alone. The chance of detecting a TAM2 profile increased by 25% per additional year of exposure to zidovudine. We found that mutations 67N and 184V were not associated with a particular TAM profile. In the presence of TAM2 profiles, the adjusted mean difference in the 6-month viral reduction was 0.96 log10 copies/ml (95% confidence interval: 0.20; 1.73) higher in patients who started stavudine-containing regimens instead of zidovudine-containing regimens. CONCLUSIONS: This study provides evidence that the suggested TAM clustering is a real phenomenon and that it may be driven by which thymidine analogue the patients has used. In patients with TAM2-resistant viruses, stavudine appears to retain greater viral activity than zidovudine.

Anti-HIV Agents↗
PubMed2004

Minor mutations in HIV protease at baseline and appearance of primary mutation 90M in patients for whom their first protease-inhibitor antiretroviral regimens failed.

The association between minor mutations in human immunodeficiency virus (HIV) protease at baseline and development of common primary mutation 90M at virological failure (conferring some resistance to all protease inhibitors [PIs]) was evaluated in 93 previously drug-naive patients experiencing failure of their first PI-based antiretroviral regimens. In logistic regression analysis, the probability of accumulating a new 90M mutation at virological failure was associated with the presence at baseline of minor mutation 36I (naturally occurring in approximately 25% of HIV clade B and in >80% of HIV non-clade-B viruses) (adjusted odds ratio, 13.5 [95% confidence interval, 1.89-95.6]; P=.009) and, possibly, of 10I/V. This suggests a potential role for the presence of 36I at baseline in predicting the appearance of 90M at virological failure.

Antiretroviral Therapy, Highly Active↗
PubMed2004

Risk of failure in patients with 215 HIV-1 revertants starting their first thymidine analog-containing highly active antiretroviral therapy.

OBJECTIVE: To investigate the impact of 215 HIV-1 revertants on the risk of virological failure of the first thymidine analog-containing highly active antiretroviral therapy (HAART). DESIGN: The study included 491 HIV-1 subjects of the Italian Cohort Naive for Antiretrovirals, 405 of whom received a genotypic assay before therapy and had a virological follow-up. METHODS: Pre-treatment genotypic resistance was assessed by sequencing of the whole protease (PR) and reverse transcriptase (RT) region. RESULTS: Three (3.2%) and 13 (3.3%) individuals with recent (n = 95) and chronic (n = 396) HIV-1 infection carried an HIV-1 strain with 215 revertants (215D/C/E/A/V), respectively. In contrast, nucleoside associated mutations were higher in the former (15.8%) compared with the latter group (6.8%) (P = 0.005). A multivariable regression model, considering pre-HAART viral load levels, use of saquinavir-hard gel as the only PI, use of zidovudine, number of other RT and PR mutations, indicated that patients carrying 215 revertants had an increased risk of virological failure compared with those not carrying such mutants (adjusted relative hazard = 2.97 95% confidence interval, 1.11-7.94, P = 0.03). Among patients with 215 revertants, who experienced virological failure, four out of seven showed the emergence of the 215Y resistant mutation. The probability of 215Y occurrence was different between patients carrying 215 revertants compared with those who did not carried these mutants (P = 0.006). CONCLUSIONS: HIV-1 215 revertants with an increased ability for selecting 215Y mutation are associated with a higher risk of virological failure and may lead to the appearance of virus carrying 215Y/F mutation in vivo. These findings suggest that 215 revertant viruses may compromise the efficacy of the first thymidine analog-containing regimen.

Adult↗
PubMed2004

Relative prognostic value of self-reported adherence and plasma NNRTI/PI concentrations to predict virological rebound in patients initially responding to HAART.

We studied the predictive value of self-reported adherence and plasma drug concentrations on virological rebound to HAART. Among 238 participants in the AdICoNA study who had viral load < or = 500 copies/ml, 42 (17.6%) experienced virological rebound by 96 weeks. Both self-reported non-adherence and sub-optimal concentration were independently associated with a higher risk of virological rebound.

Anti-HIV Agents↗
PubMed2004

Variability in the interpretation of transmitted genotypic HIV-1 drug resistance and prediction of virological outcomes of the initial HAART by distinct systems.

High level HIV-1 drug resistance in recently infected treatment-naive individuals correlates with sub-optimal virological responses to highly active antiretroviral therapy (HAART). To determine whether genotypic HIV-1 drug resistance in chronic naive patients, as interpreted by various systems, could predict the virological outcomes of HAART, isolates from patients enrolled in a prospective observational cohort (ICoNA) prior to treatment start were genotyped. Genotypic susceptibility scores (GSS) assigned to the initial HAART regimens using the interpretations of pre-therapy resistance mutations by 13 systems were related to virological outcomes. Of 415 patients, 42 (10%) had at least one major resistance mutation. According to the different interpretations, 1.9-20.5% of patients had some level of resistance to at least one drug in the initial regimen. In multivariable analysis, GSS from two systems significantly predicted the time to virological success: Rega 5.5, for each unit increase in GSS adjusted relative hazard (RH) 1.86 [95% confidence intervals (95% CI): 1.15-3.02] and hivresistanceWeb v3, RH 1.87 (95% CI: 1.00-3.48). With three other systems, GSS showed a trend towards a significant prediction of success: Retrogram 1.6, RH 2.33 (95% CI: 0.98-5.53), Menéndez 2002, RH 2.36 (95% CI: 0.97-5.72) and Stanford hivdb, RH 2.06 (95% CI: 0.94-4.49). Genotypic resistance testing coupled with adequate interpretation in chronic naive patients can usefully identify those at risk of sub-optimal virological response to HAART. This work was presented in part at the First European Workshop on HIV Drug Resistance. Luxembourg, 4-6 March 2003 (Abstract 44); and at the 9th European Conference on CIinical AIDS Therapy. Warsaw, 25-28 October 2003 (Abstract F6/7).

Adult↗
PubMed2004

Baseline resistance and virological outcome in patients with virological failure who start a regimen containing abacavir: EuroSIDA study.

OBJECTIVES: To investigate the ability of several HIV-1 drug-resistance interpretation systems, as well as the number of pre-specified combinations of abacavir-related mutations, to predict virological response to abacavir-containing regimens in antiretroviral therapy-experienced, abacavir-naive patients starting an abacavir-containing regimen in the EuroSIDA cohort. PATIENTS AND METHODS: A total of 100 HIV-infected patients with viral load (VL) >500 copies/ml who had a plasma sample available at the time of starting abacavir (baseline) were included. Resistance to abacavir was interpreted by using eight different commonly used systems that consisted of rules-based algorithms or tables of mutations. Correlation between baseline abacavir-resistance mutations and month 6 virological response was performed on this population using a multivariable linear regression model accounting for censored data. RESULTS: The baseline VL was 4.36 log10 RNA copies/ml [interquartile range (IQR): 3.65-4.99 log10 RNA copies/ml] and the median CD4 cell count was 210 cells/microl (IQR: 67-305 cells/microl). Our patients were pre-exposed to a median of seven antiretrovirals (2-12) before starting abacavir therapy. The median (range) number of abacavir mutations (according to the International AIDS Society-USA) detected at baseline was 3.5 (0-8). Overall, the Kaplan-Meier estimate of the median month 6 VL decline was 0.86 log10 RNA copies/ml [95% confidence intervals (95% CI): 0.45-1.24]. The VL in those patients (n=31) who intensified treatment by adding only abacavir decreased by a median 0.20 log10 RNA copies/ml (95% CI: -0.18; +0.94). The proportion of patients who harboured viruses fully resistant to abacavir among the eight genotypic resistance interpretation algorithms ranged from 12% [Agence Nationale de Recherches sur le SIDA (ANRS)] to 79% [Stanford HIV RT and PR Sequence Database (HIVdb)]. Some interpretation systems showed statistically significant associations between the predicted resistance status and the virological response while others showed no consistent association. The number of active drugs in the regimen was associated with greater virological suppression (additional month 6 VL reduction per additional sensitive drug=0.51, 95% CI: 0.15-0.88, P=0.006); baseline VL was also weakly associated (additional month 6 VL reduction per log10 higher=0.30, 95% CI: -0.02; +0.62, P=0.06). In contrast, the number of drugs previously received was associated with diminished viral reduction (additional month 6 VL reduction per additional drug=-0.14, 95% CI: -0.28; 0.00, P=0.05). CONCLUSIONS: Our results revealed a high degree of variability among several genotypic resistance interpretation algorithms currently in use for abacavir. Therefore, the interpretation of genotypic resistance for predicting response to regimens containing abacavir remains a major challenge.

Adult↗