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The Body Covers: The 39th Annual Meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy
Slide Session 202.I: Antiretroviral Therapy in Clinical Practice

September 29, 1999

Paper No. 2064: Management of Protease Inhibitor (PI)-Associated Lipodystrophy by Substitution with Efavirenz (EFV) in Virologically Controlled HIV-Infected Persons

Paper No. 2065: The Efficacy of Ritonavir (RTV)/Saquinavir (SQV) Antiretroviral Therapy (ART) in Patients Who Failed Nelfinavir (NFV): A Multi-Center Clinical Cohort Study

Paper No. 2066: Virological and Clinical Response to Second Line Protease Inhibitor-Containing Regimens

Paper No. 2067: Multi-Drug Rescue Therapy (MDRT) for HIV-Infected Individuals with Prior Virological Failure to Multiple Regimens -- Results from Two Cohorts

Paper No. 2068: Phenotypic Resistance to Protease Inhibitors Predicts Outcome of a Five Drug Combination Including Ritonavir, Saquinavir and Efavirenz in Patients Who Failed on HAART

Paper No. 2069: Serum Protease Inhibitor Level as a Marker of Adherence to HAART: Correlation with Self-Reported Adherence and with HIV RNA


Oral presentations in this session dealt with issues around decreasing protease inhibitor side effects by switching regimens, salvage regimens in treatment experienced patients with virologic failure, utility of resistance testing in predicting responses to salvage regimens and assessment tools of patient adherence to antiretroviral regimens.


Paper No. 2064: Management of Protease Inhibitor (PI)-Associated Lipodystrophy by Substitution with Efavirenz (EFV) in Virologically Controlled HIV-Infected Persons

Authored by G. J. Moyle, et al.
Coverage provided by Mark Holodniy, M.D.

Presentation 2064 asked the question of whether substituting efavirenz for a protease inhibitor in patients who were NNRTI naïve and with undetectable viral loads could maintain this virologic response and decrease the lipodystrophy (fat redistribution) problems that patients had developed on the protease inhibitor regimen. Twenty-nine patients were followed up to 48 weeks. Patients stayed on their NRTI drugs, although 5 added abacavir. All patients maintained their viral load at <50 copies/ml. CD4 count increases from 30-100 cells was also seen. There was no significant change in triglyceride or cholesterol levels. Insulin levels decreased in some patients, which resulted in improved glucose tolerance tests. Weight increased by about 5-7 pounds, which was associated with an increase in fat free mass and a marked decrease in visceral (internal abdominal) adipose tissue. Although some patients demonstrated some redistribution of fat, in general little normalization was seen. The conclusion from this paper was that substitution of an NNRTI in someone receiving a PI containing regimen is safe, maintains virologic efficacy and may result in some improvement in the lipodystrophy syndrome after 48 weeks.


Paper No. 2065: The Efficacy of Ritonavir (RTV)/Saquinavir (SQV) Antiretroviral Therapy (ART) in Patients Who Failed Nelfinavir (NFV): A Multi-Center Clinical Cohort Study

Authored by A. Zolopa, et al.
Coverage provided by Mark Holodniy, M.D.

Presentation 2065 presented data on whether a second PI containing regimen could be effective in patients who had failed the first PI containing regimen. About 90 patients who had failed nelfinavir (average duration of nelfinavir therapy = 11 months) as determined by virologic rebound, were switched to a PI regimen consisting of ritonavir and saquinavir (usually 400mg/400mg twice daily of each). Seventeen had received prior NNRTI therapy. In addition, 50% added one new NRTI and 25% added 2 new NRTI. At the time of the switch, mean CD4 count was 259 and viral load about 30,000 copies/ml. Genotyping revealed that 50% had resistance to nelfinavir at baseline. Six patients had evidence of saquinavir resistance (codon 90 change). After 6 months of therapy, 67% of the on treatment (OT) group (those who were still receiving the regimen) had a viral load of <500. In intent to treat (ITT) analysis where those people who did not complete 6 months were considered therapy failures, 50% achieved a viral load of <500/ml. CD4 counts increased on average by 100 cells. In fifteen patients who were analyzed, 10 of 15 with genotypic nelfinavir resistance achieved a viral load of <500 at 6 months. Having nelfinavir resistance was not predictive of a response. Thus, substituting this duel PI containing regimen in patients who have failed nelfinavir may be a useful second regimen. Whether this strategy will have a durable response and how many of these people achieved a viral load of <50 copies/ml remains to be reported.


Paper No. 2066: Virological and Clinical Response to Second Line Protease Inhibitor-Containing Regimens

Authored by A. Phillips, et al.
Coverage provided by Mark Holodniy, M.D.

Presentation 2066 described observational data from the EuroSIDA (multinational European AIDS) study on their experience with 2nd PI containing regimens. Data from 942 patients who had had at least 16 weeks of one PI containing regimen was presented. The mean baseline viral load was 6,000 copies/ml and CD4 count was 160. There were no patients who had received nelfinavir as a first regimen. The proportion of 2nd PI containing regimens was: nelfinavir (31%), indinavir (45%), ritonavir (18%), saquinavir (8%). Over half did not add/change their NRTI component, and 35% changed one NRTI. The mean viral load reduction after one year was 0.8 log/ml (<than 10 fold). Less than 40% of patients achieved a viral load <500 copies/ml. When those patients with viral loads of >100,000 were analyzed separately, only 20% achieved a viral load of <500. CD4 counts increased by an average of 75 cells. Using a proportional hazards model, predictors of an undetectable viral load included: baseline viral load of < 10,000; addition of 2 or more new NRTI; high baseline CD4 count; and having achieved a viral load of <500/ml with the first PI containing regimen. Although the aggregate data would suggest that few patients can achieve virologic benefit from second PI regimens, more analysis is need to determine which subset of patients might optimally benefit from this strategy.


Paper No. 2067: Multi-Drug Rescue Therapy (MDRT) for HIV-Infected Individuals with Prior Virological Failure to Multiple Regimens -- Results from Two Cohorts

Authored by J. S. G. Montaner, et al.
Coverage provided by Mark Holodniy, M.D.

Presentation 2067 described a Canadian experience with multiple-drug rescue therapy (MDRT) in patients who had previously failed many prior regimens. Two groups distinguished by an earlier less intense (98 patients, 1 year follow-up) and later more intense regimen (65 patients, 5 month follow-up) was presented. Up to 9 drugs including 4 NRTI/2NNRTI/2PI/hydroxyurea were used. The groups were evenly matched in terms of CD4 count (mean 175, 200), viral load (62,000, 55,000) and past antiretroviral experience (43, 40 months). In both groups, over half were able to achieve at least one viral load <400/ml. However the durability was limited in the majority of patients. In both the ITT and OT analyses, only a third of patients had sustained viral loads <400/ml. Some phenotypic resistance results were briefly presented. A formal analysis of correlation between response and presence or absence of resistance to the multiple agents was not described. Severe or serious adverse drug reactions were experienced by 16% of the group and 39% had to change the regimen because of toxicities. Nonetheless, this study did demonstrate that aggressive recycling of agents could still achieve a significant virologic effect in some patients.


Paper No. 2068: Phenotypic Resistance to Protease Inhibitors Predicts Outcome of a Five Drug Combination Including Ritonavir, Saquinavir and Efavirenz in Patients Who Failed on HAART

Authored by C. Piketty, et al.
Coverage provided by Mark Holodniy, M.D.

Presentation 2068 described a French experience with PI salvage in patients who had previously failed indinavir or ritonavir containing regimens. 32 patients who were saquinavir naïve, with mean CD4 count of 295 and viral load >5,000/ml, had their regimen changed to saquinavir (1000mg twice daily), ritonavir (100mg twice daily), efavirenz (600mg once daily), and recycled NRTIs. At baseline the majority of patients had evidence of phenotypic resistance to indinavir and ritonavir. 40% had phenotypic and genotypic evidence of saquinavir resistance. 77% had genotypic evidence of secondary PI mutations. After 48 weeks of therapy, the mean increase in CD4 count was 100 cells. Viral load decreased by a mean of 1.5 log/ml. About 60% of the group had achieved a viral load of <500/ml. Patients with phenotypic evidence of saquinavir resistance at baseline had a significantly lower decrease in viral load, and were less likely to achieve an undetectable viral load than those patients who were sensitive to saquinavir. In this study phenotypic resistance testing was more predictive than genotypic resistance testing of a virologic response. However, this was a small study and may have underestimated the predictive value of genotyping. In addition, this and the above studies have used a viral load cutoff of 500 copies, and so the long-term durability (i.e <50 copies/ml) of these PI salvage regimens is not clear yet.


Paper No. 2069: Serum Protease Inhibitor Level as a Marker of Adherence to HAART: Correlation with Self-Reported Adherence and with HIV RNA

Authored by M. Duong, et al.
Coverage provided by Mark Holodniy, M.D.

Finally presentation 2069 studied whether self reported adherence to HAART regimens correlated with viral load response and trough blood levels of PIs. 149 patients receiving a HAART regimen were given an adherence questionnaire to fill out. Viral load and trough PI levels were obtained. A viral load response of >2 log/ml and >1 log/ml for drug naïve and experienced patients respectively was considered a good response. Self-reported good adherence was reported by 65% of the patients, of whom, 85% were considered to have had a good viral load response. When serum therapeutic PI levels were considered, 82% would be considered adherent, of whom, 83% were considered to have had a good viral load response. Self reported adherence and serum levels were significantly associated with virologic response. However, serum levels were considered a somewhat better predictor of adherence (as measured by viral load response) than self-assessment. More data continues to be generated that indicates that patients are not accurate in their self-assessment of regimen adherence. Other tools such as serum drug levels, MEMS caps, direct pill counting, prescription refill audits may also help the practitioner in the assessment of medication adherence.



  
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Please note: Knowledge about HIV changes rapidly. Note the date of this summary's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this summary. For a complete listing of our most recent conference coverage, click here.

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