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At least 1,639 records · Page 91Linked to original sources
PubMed1998

Clinical experience with adding delavirdine to combination therapy in patients in whom multiple antiretroviral treatment including protease inhibitors has failed.

OBJECTIVE: To determine the effectiveness and safety of adding delavirdine mesylate to a treatment regimen that included indinavir and nucleoside analog reverse transcriptase inhibitors in patients in whom combination therapy had failed. DESIGN: Observational study. SETTING: Private practice. PATIENTS: HIV-1-positive patients with peripheral blood CD4+ lymphocyte counts < 300 x 10(6)/l in whom antiretroviral therapy had failed or whose condition was deteriorating. Of the 53 patients who were eligible for the study, 47 took part; for the majority of these patients indinavir combination therapy had been unsuccessful. the majority of the patients were male (98%), white (92%) and homo/bisexuals (96%). INTERVENTIONS: Delavirdine added to current therapy (usually zidovudine, indinavir and lamivudine); in approximately half of the patients zidovudine was replaced with stavudine. MAIN OUTCOME MEASURES: Plasma HIV-1 RNA levels; peripheral blood CD4+ and CD8+ lymphocyte counts. Safety of the therapy was assessed by monitoring side-effects. RESULTS: Mean baseline CD4+ lymphocyte count was 127 x 10(6)/l and mean baseline HIV-1 plasma RNA was 5 log10 copies/ml. Adding delavirdine to the therapeutic regimen produced a rapid and sustained decrease in the mean plasma HIV-1 RNA of 1.1 log10 copies/ml over 6 months; 18-21% of patients showed decreases of 2-3 log10 copies/ml. Viral burden in 33% of subjects declined below the assay's limit of detection (2.6 log10 copies/ml) after 6 months. CD4+ lymphocyte counts increased by 66-90% in each group between 1 and 9 months (mean increase approximately 60 x 10(6)/l after 6 months). Adding delavirdine to current therapy was well tolerated. Side-effects reported were: skin rash, 28%; nausea, 9%; kidney stones, 9%; diarrhea, 6%; flank pain, 2%; proteinuria, 2%. Three patients reported serious medical events all of which resolved and none of which were attributed to delavirdine. CONCLUSIONS: Adding delavirdine to the combination regimen of patients in whom protease inhibitor therapy had failed often resulted in a rapid and remarkable decrease in viral load, sustained improvement in CD4+ lymphocyte counts and viral load, and clinical improvement with minimal toxicity.

Adult↗
PubMed1996

Role of altered metabolism in dideoxynucleoside pharmacokinetics. Studies of 2'-beta-fluoro-2',3'-dideoxyinosine and 2'-beta-fluoro-2',3'-dideoxyadenosine in rats.

Enzymes of the purine salvage pathway play an important role in altering the in vivo pharmacokinetics of 2',3'-dideoxypurine nucleosides. This study examines the pharmacokinetics of enzyme-resistant 2'-beta-fluoro analogues of 2',3'-dideoxyinosine (ddI) and 2',3'-dideoxyadenosine (ddA). 2'-beta-Fluoro-2',3'-dideoxyinosine (F-ddI) is an acid-stable analogue of ddI that is highly resistant to purine nucleoside phosphorylase, the principal enzyme in ddI metabolism. 2'-beta-Fluoro-2',3'-dideoxyadenosine (F-ddA), an acid-stable and purine nucleoside phosphorylase-resistant analogue of ddA, is converted in vivo to F-ddI by adenosine deaminase (ADA) but is a much poorer substrate for this enzyme than is ddA. Both F-ddA and F-ddI have been shown to have activity against human immunodeficiency virus in vitro, and F-ddA has been selected by the National Cancer Institute for clinical trials as a new human immunodeficiency virus reverse transcriptase inhibitor. The pharmacokinetics of F-ddI and ddI were compared at equivalent doses in chronically catheterized rats. Because ddI and F-ddI are isosteres having nearly identical lipophilicity, this comparison is likely to reflect primarily metabolic differences. The clearance of F-ddI was substantially reduced, in comparison with that of ddI (27.3 ml/min/kg vs. 90.9 ml/min/kg), resulting in higher systemic concentrations at steady state and prolonged retention of F-ddI after termination of infusions, consistent with a significant metabolic component in the clearance of ddI. Concentrations of F-ddA and F-ddI during and after infusions of F-ddA were determined in both untreated and 2'-deoxycoformycin-pretreated rats. In untreated rats, F-ddA was rapidly eliminated from plasma, with a total clearance of 68.5 ml/kg/min. Metabolic clearance of F-ddA to F-ddI accounted for 58% of this value (bioconversion t1/2 = 9.8 +/- 1.9 min). Pretreatment with 2'-deoxycoformycin, an ADA inhibitor, reduced the clearance of F-ddA to 23.8 ml/min/kg, leading to 2.9 +/- 0.4-fold higher steady-state plasma concentrations of F-ddA, in agreement with a 2.5-fold enhancement predicted by a compartmental model assuming complete ADA inhibition.

Adenosine Deaminase Inhibitors↗
PubMed2004

Once-daily saquinavir and ritonavir in treatment-experienced HIV-1-infected individuals.

To assess the efficacy of 48 weeks' treatment with saquinavir 1600 mg and ritonavir 100 mg, both given once daily (SQVOD), in drug-experienced HIV-infected patients, a SQVOD-based therapy was offered to 100 treatment-experienced patients via their own physicians. The patients starting this regimen were followed up for 48 weeks. HIV-RNA was assessed by means of NASBA (limit of quantification = 80 copies/mL). Fifteen patients received the SQVOD-based therapy. Six discontinued before week 48 because of failure, toxicity or intolerance due to the high pill burden and gastrointestinal side effects. The median baseline CD4+ cell counts and plasma HIV-RNA levels were 317 cells/microL (range 44-698) and 4.18 log copies/mL (range 2.65-6.18). At week 4, there was a mean decrease of 1.96 log copies/mL (P < 0.0001) in HIV-RNA, with 75% of the patients having fewer than 400 copies/mL; seven of the nine patients treated for 48 weeks reached fewer than 400 copies/mL. No substantial change in cholesterol or triglyceride values was observed over 48 weeks. As this SQVOD-based regimen had considerable short-term virologic activity in treatment-experienced HIV-infected patients, it may be a reasonable option when non-nucleoside reverse transcriptase inhibitors cannot be administered and once-daily dosing is preferred by the patient. However, the high pill burden and frequent gastrointestinal side effects of the soft gel capsule formulation of saquinavir may limit its long-term efficacy.

Adult↗
PubMed1999

Why is highly active antiretroviral therapy (HAART) not prescribed or discontinued? Swiss HIV Cohort Study.

In this cross-sectional survey conducted at the end of 1997 among the physicians of participants of the Swiss HIV Cohort Study (SHCS), 1487 of 2154 patients (69.0%) were treated with highly active antiretroviral treatment (HAART) defined as triple therapy with a combination of one or two reverse transcriptase inhibitors, and one or two protease inhibitors; 541 patients (25.1%) had never received such treatment. The physician's perception that the patient would not comply with treatment was one reason for not prescribing HAART to 20% of these patients (110). Physicians indicated that the most common reasons for the patient to refuse HAART were the fear of side effects (18%) and the patient's perception that treatment was too complicated (18%). Among 126 patients (5.8%) no longer receiving HAART, the most common reasons for discontinuing treatment were actual side effects (61%) or the fear of side effects (25%). Overall, 16% of patients did not receive therapy in accord with official Swiss guidelines. Multivariate logistic regression analysis indicated that patients with lower education, active intravenous drug users outside of a drug substitution program, and those who acquired HIV infection through intravenous drug use had a significantly higher risk of inadequate treatment. The physician's judgment of patient adherence and the physician's perception of the patient's fear of side effects are critical for the prescription of HAART. Physicians should address these issues to prevent unilateral withholding of treatment and increase the proportion of patients who may benefit from current antiretroviral therapy.

Anti-HIV Agents↗
PubMed1992

Non-nucleoside inhibitors of HIV reverse transcriptase: screening successes--clinical failures.

A little less than two years ago, the first report describing non-nucleoside inhibitors of HIV reverse transcriptase (RT) led to the high anticipation that a range of new drugs could soon be available for the treatment of AIDS. The intervening period has given rise to several such agents but recent clinical trial data has indicated this optimism to be premature. This short review seeks to trace the brief history of the drug discovery process and to assess whether there are lessons to be learnt from the episode.

Antiviral Agents↗
PubMedDate not supplied

Effectiveness and tolerability of nevirapine, stavudine, and lamivudine in clinical practice.

BACKGROUND: Recent studies reveal patients on protease inhibitor (PI)-based regimens achieve viral suppression less often in clinical practice than in clinical trials. Nonnucleoside reverse transcriptase inhibitors (NNRTIs) can provide an equally effective and more convenient alternative. PURPOSE: This retrospective chart review examines the effectiveness, tolerability, and convenience of a nevirapine (NVP), stavudine (d4T), and lamivudine (3TC)-containing regimen in an urban HIV clinical practice. METHOD: Chart review of patients from September 1996 to April 2000 yielded 73 patients on NVP+d4T+3TC; 83.6% were treatment experienced. RESULTS: By 16 weeks, 86.4% (57/66) had viral loads (VL) <400 in an as-treated (AT) analysis, while 78.1% (57/73) had VL <400 in an intent-to-treat (ITT) analysis. By 24 weeks, 84.6% (33/39) had VL <50 (AT). Beyond 48 weeks, 88.9% (16/18) had VL <50. The mean CD4 increase was 170 cells/mm(3). Rash was the most common adverse event (13.7%) in this review. CONCLUSION: Consistent with other studies, this NVP+d4T+3TC regimen appears effective in both treatment-experienced and -naive patients, regardless of baseline viral loads, in a clinical practice setting.

Adult↗
PubMed2002

Predictors of undetectable plasma viral load in HIV-positive adults receiving antiretroviral therapy in Southern Brazil.

Factors associated with undetectable viral load (<80 copies/ml) were investigated among non-pregnant adults in antiretroviral treatment in a specialized service for HIV/AIDS in Southern Brazil. Use of antiretrovirals was investigated in two interviews (one month interval). Clinical data were collected from the clinical records; viral load previous to adherence measurement was defined the viral load previous to the first interview; the final viral load, the viral load subsequent to the second interview (interval between measures approximately 6 months). Undetectable final viral load occurred in 48% of the patients and was positively associated with levels of treatment adherence (p<0.001), being 19% for less than 60% of adherence and about 60% for adherence greater than 80%. In the multivariate model, the odds of undetectable final viral load was four times greater for 80-94% and > or =95% of adherence (CI 95% 1,80-13,28; CI 95% 1,73-9,53), compared with less than 60% adherence; it was greater for less than 6 months in treatment (OR = 3.37; CI 95% 1.09-10.46); and smaller for viral load previous to adherence measurement 5.2 log10 (OR = 0.19; CI95% 0.06-0.58), adjusted for these variables and sex, age, clinical status, current immune status, group of drugs and interval between the two measurements of viral load. The crude odds were lower for age 16-24 years and use of Nucleoside Analog Reverse Transcriptase Inhibitors only, but these effects were not significant in the multivariate model. There was no evidence of effect of sex, clinical status, current immune status, and changes in treatment regimen. Treatment adherence gave the largest effect. Motivational interventions directed at adherence may improve treatment effectiveness.

Adolescent↗
PubMed1999

Bridging the gap. Bringing new antiretroviral medications into the clinic.

Highly active antiretroviral therapy (HAART) is a strategy in which clinicians introduce potent combinations of antiretroviral medications early in the course of HIV infection. The intent is to suppress viral replication as completely as possible to forestall irreversible immune system damage. Antiretroviral agents fall into two major classes reverse transcriptase inhibitors and protease inhibitors. Each class interferes with viral replication at a different point in the viral life cycle. Recent research findings demonstrate clearly that antiretroviral treatment should begin as soon as the patient is willing and able to take the multidrug regimens. The best strategy for meeting the challenge of antiretroviral resistance is prevention. If you completely halt viral replication with potent therapy, the development of resistant strains is prevented.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Gene therapy for HIV/AIDS: the potential for a new therapeutic regimen.

Human Immunodeficiency Virus (HIV) is the etiologic agent of Acquired Immunodeficiency Syndrome (AIDS). HIV/AIDS is a disease that, compared with the not so distant past, is now better held in check by current antiretroviral drugs. However, it remains a disease not solved. Highly active antiretroviral therapy (HAART) generally uses two non-nucleoside and one nucleoside reverse transcriptase (RT) inhibitor or two non-nucleoside RT and one protease inhibitor. HAART is far more effective than the mono- or duo-therapy of the past, which used compounds like the nucleoside reverse transcriptase inhibitor AZT or two nucleoside reverse transcriptase inhibitors. However, even with the relatively potent drug cocktails that comprise HAART, there are the issues of (i). HIV escape mutants, (ii). an apparent need to take the drugs in an ongoing manner, and (iii). the drugs' side effects that are often severe. This review speaks to the potential addition to these potent regimens of another regimen, namely the genetic modification of target hematopoietic cells. Such a new treatment paradigm is conceptually attractive as it may yield the constant intracellular expression of an anti-HIV gene that acts to inhibit HIV replication and pathogenicity. A body of preclinical work exists showing the inhibition of HIV replication and decreased HIV pathogenicity by anti-HIV genetic agents. This preclinical work used hematopoietic cell lines and primary cells as the target tissue. More recently, several clinical trials have sought to test this concept in vivo.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Hydroxyurea: mechanisms of HIV-1 inhibition.

Hydroxyurea inhibits cellular ribonucleotide reductase, resulting in decreased pools of dNTPs and thus inhibition of DNA synthesis. Studies in vitro have shown that hydroxyurea reduces dNTP pools in cells infected with human immunodeficiency virus type 1 (HIV-1), inhibiting HIV-1 DNA synthesis in infected quiescent and activated primary human lymphocytes and macrophages. Hydroxyurea also potentiates the activity of nucleoside reverse transcriptase inhibitors (NRTIs): the activated triphosphate forms of NRTIs compete with naturally occurring dNTPs for incorporation into nascent viral DNA during reverse transcription. A synergistic effect is observed between hydroxyurea and didanosine (2',3'-dideoxyinosine; DDI). This combination exerts persistent suppression of HIV-1 replication without evidence of viral rebound for over 1 year in HIV-1-infected patients. Didanosine-resistant HIV-1 mutants retain sensitivity to didanosine in the presence of hydroxyurea. The incorporation of didanosine triphosphate by resistant reverse transcriptase is increased in the context of the hydroxyurea-induced depletion of dATP. Although hydroxyurea has a reduced effect on dNTPs competing with the triphosphate forms of pyrimidine NRTIs, it appears to augment the anti-HIV-1 activity of these agents by increasing their intracellular phosphorylation; this may be of particular interest for salvage strategies given recent data indicating disruption of NRTI phosphorylation with specific NRTI treatment regimens. Finally, by exerting a cytostatic effect on CD4 and CD8 T lymphocytes, hydroxyurea may (i) reduce HIV-1 replication by decreasing CD4 T cell proliferation; and (ii) prevent the exhaustion of CD8 T cell populations that may occur as a result of excessive activation in the context of HIV-1 infection.

Deoxyribonucleotides↗
PubMed1995

Activity of various thiocarboxanilide derivatives against wild-type and several mutant human immunodeficiency virus type 1 strains.

A large variety of carboxanilide derivates in which the original oxathiin moiety present in the prototype compound UC84 was replaced by a non-cyclic lipophilic entity has been evaluated for their inhibitory effect against wild-type human immunodeficiency virus type 1 (HIV-1/IIIB) and several mutant viruses derived thereof (i.e. HIV-1/138-Lys, HIV-1/181-Cys, HIV-1/106-Ala and HIV-1/100-IIe). Isopropoxy was the most favorable substituent resulting in molecules that were markedly inhibitory to the wild-type (EC50 0.004-0.04 microgram/ml) as well as the mutant HIV-1 strains (EC50 0.06-0.75 microgram/ml). In this respect, they proved superior to several other HIV-1-specific non-nucleoside reverse transcriptase inhibitors (NNRTIs) that are currently the subject of clinical trials. One of the most potent HIV-1 inhibitors among the thiocarboxanilide derivatives, namely UC38, selected for a mutant virus strain in which Lys at position 101 and Gly at position 190 of the reverse transcriptase was replaced by Glu.

Antiviral Agents↗
PubMedDate not supplied

Self-reported symptoms after initiation of a protease inhibitor in HIV-infected patients and their impact on adherence to HAART.

PURPOSE: The purpose of our study was to assess short-term self-reported symptoms in patients who were started on two nucleoside reverse transcriptase inhibitors and one protease inhibitor (PI) in the multicenter APROCO cohort (N = 336) and to assess the influence of these symptoms on adherence. METHOD: Adherence and patient's reported symptoms were measured at 1 and 4 months (M) after initiation of highly active antiretroviral therapy (HAART) through self-administered questionnaires. RESULTS: Most patients reported at least one symptom (94.0% at M1; 88.0% at M4); fatigue and diarrhea were the most often reported symptoms. Respectively, 81.3% and 75.0% of patients were strictly adherent to HAART during the 4 days prior to M1 and M4 visits. After adjustment for younger age, history of antiretroviral treatment, unstable housing, poor social support, and alcohol consumption, patients who reported a high number of symptoms at M1 were more likely to be nonadherent at M4 (odds ratio per symptom = 1.13; 95% CI = 1.03-1.24). CONCLUSION: Patients reporting a high number of symptoms soon after HAART initiation are at higher risk of future nonadherence and could be targeted for interventions to achieve good levels of adherence and to improve treatment outcome.

Adult↗
PubMed2000

Rapid phenotypic drug susceptibility assay for HIV-1 with a CCR5 expressing indicator cell line.

Phenotypic drug susceptibility assays of human immunodeficiency virus type 1 (HIV-1) isolates generally use time-consuming, expensive assays with peripheral blood mononuclear cells. A new HIV-1 indicator cell line, MAGI-CCR5, has been developed and applied for this purpose. This cell line expresses human CD4, the two major HIV-1 coreceptors, CCR5 and CXCR4, the reporter gene beta-galactosidase driven by the HIV-1 LTR, and quantitates infection within 48 h. A panel of reference strains and primary HIV-1 isolates were all found to infect this cell line. Susceptibility assays with a nucleoside (zidovudine, ZDV) and a non-nucleoside reverse transcriptase inhibitor (nevirapine, NVP) were performed with reference and primary isolates. The assay was modified into two steps for protease inhibitor (indivinavir, IDV and ritonavir, RTV) susceptibility assays. Primary isolates derived from drug naive patients displayed mean baseline 50% effective concentrations (EC50) of 0.14 microM for ZDV, 0.33 microM for NVP, and 0.02 microM for IDV. Isolates derived from patients under treatment displayed increased EC50 concentrations. The MAGI-CCR5 cell line offers a rapid, efficient, and reproducible method of testing a wide range of HIV-1 isolates for drug susceptibility.

Anti-HIV Agents↗
PubMed2000

Nature of equilibria and effects of drug treatments in some simple viral population dynamical models.

We examine some simple mathematical models which have been recently employed to predict the evolution of population dynamical systems involving virus particles. They include: (1) A general two-component antibody-viral system; (2) A simplified two-component model for HIV-1 dynamics (3) An HIV-1 three-component model including virions and (4) A four-component HIV-1 dynamical model which includes both latently and actively infected cells. For each system we find equilibrium points and analyse their local stability properties in order to obtain a global phase portrait. Analytical methods are complemented with numerical solutions. In all four models there are at most two equilibrium points for physically meaningful values of the variables. As the viral growth rate parameter increases through a critical value, a transcritical bifurcation occurs. One critical point (P1) is always found at zero viral or infected cell levels and non-zero antibody or uninfected cell levels. For parameter values in their usual ranges, P1 is either an asymptotically stable node or a saddle point. When the critical point P2 occurs at biologically meaningful values, it is either an asymptotically stable node or an asymptotically stable spiral point. For all three HIV-1 models, the values of the parameters at which P2 makes a transition to physically meaningful values are precisely those at which P1 changes from an asymptotically stable node to an unstable saddle point. The global pictures for all four models are similar and examples are represented graphically. No limitcycle solutions were found in any of the models for parameter values in their usual ranges. In the four-component HIV-1 model, the effects of varying each parameter are found and conditions under which P2 changes from spiral point to node are investigated numerically. The effects of reverse transcriptase inhibitors and protease inhibitors, two classes of drugs used to treat HIV-1 infection, are examined in the three-component model for early HIV-1 dynamics.

HIV Antibodies↗
PubMedDate not supplied

Efficacy of nelfinavir in patients switched from ritonavir/saquinavir combination antiretroviral therapy.

UNLABELLED: Based on available data and expert opinion, the IAS-USA treatment guidelines recommend "selective substitution" of the medication thought most likely to be causing a side effect for one that should have a different side effect profile. PURPOSE: This study evaluates the short-term virological efficacy of selective substitution with nelfinavir-nucleoside combination therapy in individuals with plasma viral RNA below 400 copies/mL. METHOD: This study involved a retrospective chart review at five large urban HIV Clinical practice settings and included 19 patients taking combination therapy including ritonavir with saquinavir. We performed selective substitution with a nelfinavir combination. Our main outcome measure was plasma HIV-1 RNA (Amplicor) obtained during the period between weeks 12 to 18. RESULTS: We identified 19 HIV-1-infected individuals with evidence of viral suppression as defined by a viral load below 400 copies/mL while taking dual nucleoside reverse transcriptase inhibitors with ritonavir/saquinavir. Reasons for switching included adverse effects (37%) or preference for nelfinavir due to the possibility of a better defined salvage regimen (63%). We defined a composite viral endpoint indicative of continued viral suppression using the first 12 to 18 weeks following the medication change. We found that 73% maintained undetectable viral loads (plasma HIV RNA below 400 copies/mL) during this period. CONCLUSION: These data suggest that any medication adjustment should be made cautiously, as there may be some potential risk in a substitution. Selective substitution of a medication that has undesirable side effects or other characteristics should be considered when the possible risks of the loss of viral suppression are outweighed by the potential benefits of that substitution.

Anti-HIV Agents↗
PubMed2006

Absence of resistance mutations in antiretroviral-naive patients treated with ritonavir-boosted saquinavir.

BACKGROUND: There are few data on the selection of resistance by ritonavir-boosted saquinavir (SQV/r), particularly in antiretroviral (ARV)-naive patients. OBJECTIVE: To assess the incidence of virological failure and evolution of resistance in ARV-naive individuals receiving SQV/r in the induction phase of the Staccato trial. METHODS: ARV-naive subjects (n = 272) received SQV/r 1,600/100 mg once daily with two nucleoside reverse transcriptase inhibitors (NRTIs) for at least 24 weeks. Patients were defined as having virological failure (VF) when there were two consecutive HIV-1 RNA measurements > 500 copies/ml after week 12. Viral genotypes (reverse transcriptase [RT] and protease [PRO]) were determined at baseline in all patients and as close as possible to the time of initial failure in patients experiencing VF. RESULTS: VF was observed in 9/272 patients receiving SQV/r 1,600/100 mg once daily with two NRTIs (3.3%) and occurred 19-48 weeks after treatment initiation. Eight of these patients were evaluable at failure. No major PRO mutations were detected, but 2/8 displayed single new minor PRO substitutions (M36I, L10I) at VF that were known or suspected not to have been present at baseline; both these substitutions exist as natural polymorphisms. A third patient displayed a single new RT mutation (M184I). CONCLUSIONS: SQV/r plus two NRTIs (1,600/100 mg once daily) is an effective initial treatment option for ARV-naive patients, resulting in a low rate of viral rebound (3.3%). Furthermore, no major protease mutations were detected following VF, suggesting that future treatment options are preserved.

Adult↗
PubMed2004

Longitudinal effect of antiretroviral therapy on markers of hepatic toxicity: impact of hepatitis C coinfection.

To characterize longitudinal hepatic toxicity of antiretroviral therapy in HIV-infected women with and without hepatitis C virus (HCV) infection, we measured alanine and aspartate aminotransferase values among women initiating highly active antiretroviral therapy (HAART). For 312 HIV/HCV coinfected women who received HAART for a mean of 1.8 years, the prevalence of elevated aminotransferase levels >3 times and >5 times the upper limit of normal (ULN) was low (<12% and <4%, respectively), and the prevalence of elevated aminotransferase levels declined over time. When we analyzed trends in aminotransferase levels according to type of HAART received among HCV-infected and uninfected women, we found that mean aminotransferase levels declined among 539 women receiving therapy with protease inhibitors (decreases of 5.34%-4.23% of the ULN per year; P values for trend of.007-.06), but mean values among 128 women receiving therapy with nonnucleoside reverse-transcriptase inhibitors remained stable (from decreases of 1.65% to increases of 7.57% of the ULN per year; P values of.19-.71). Our findings lend support to assertions that antiretroviral therapy is safe for women with HCV infection.

Adult↗
PubMed2004

Understanding HIV resistance, fitness, replication capacity and compensation: targeting viral fitness as a therapeutic strategy.

The increasingly prevalent emergence of drug-resistant virus strains in patients being treated with highly active antiretroviral regimens and the increasing rates of transmission of drug-resistant virus strains have focused attention on the critical need for additional antiretroviral agents with novel mechanisms of action and enhanced potency. Furthermore, novel means of employing highly active antiretroviral therapy are needed to reduce or eliminate the virological treatment failures that currently occur. Over the past several years, evidence has mounted supporting the fact that the emergence of resistant strains is associated with reductions in viral fitness, yielding decreases in plasma virus load in treated patients harbouring resistant populations of the virus. Additional mutations that serve to modify fitness (compensatory mutations) and mutations that impact the viral replication capacity also emerge under the selective pressure of drug treatment, and have both negative and positive effects on virus growth. Fitness is generally accepted to refer to the ability of HIV to replicate in a defined environment and thus is used to describe the viral replication potential in the absence of the drug. Although viral fitness and replication capacity are related in some ways, it is important to recognise that viral fitness is not the same as viral replication capacity. This review will assess the recent literature on antiviral drug resistance, viral fitness and viral replication capacity, and discuss means by which the adaptability of HIV to respond rapidly to antiviral treatment through mutation may be used against it. This would be done by treating patients with an aim to lock the deleterious mutations into the resistant virus genome, resulting in a positive therapeutic outcome despite the presence of resistance to the selecting agents. The review will specifically discuss the literature on nucleoside and non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, fusion inhibitors, as well as other biological factors involved in viral fitness.

Anti-Retroviral Agents↗