Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Reverse Transcriptase Inhibitors”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,297 records · Page 72Linked to original sources
PubMed2003

Genotypic resistance of antiretroviral drugs among drug-naive HIV type 1 patients with the background of long-term access-easy zidovudine therapy.

The prevalence of transmitted resistance to antiretroviral drugs varies geographically, with little known about this effect in Asia. In Korea, zidovudine has been widely administered, without charge, through the National AIDS program since the early 1990s; with other potent antiretroviral agents also being introduced in the late 1990s. An analysis of the drug susceptibility to antiretroviral drugs was performed by genotyping of the drug-resistant mutations in HIV on plasma samples from 50 HIV-infected patients who had received no treatment, between February 1998 and November 2002, which was interpreted according to the consensus guidelines of the International AIDS Society-USA panel. The median CD4 cell count was 100 cells/mm3; the mean plasma RNA level was (5.19 +/- 0.56) log copies per milliliter. Of the 50 subjects tested 4 (8.0%) had one or more major drug-resistance mutation. The prevalence of resistance to multiple classes of drugs was 2.0%. No mutations, associated with resistance to non nucleoside reverse transcriptase inhibitors, were identified. Resistant mutations of the reverse-transcriptase gene were found at codons 67, 70, 118, 215, and 219, and a resistant mutation of the protease gene was found only at codon 46 (2.6%, 1 of 39). There was an 8.0% prevalence of primary drug resistance to antiretroviral drugs in Korean patients infected with HIV-1.

Adult↗
PubMed2000

Delavirdine susceptibilities and associated reverse transcriptase mutations in human immunodeficiency virus type 1 isolates from patients in a phase I/II trial of delavirdine monotherapy (ACTG 260).

The development of human immunodeficiency virus type 1 resistance to delavirdine (DLV) was studied in subjects receiving DLV monotherapy. Phenotypic resistance developed in 28 of 30 subjects within 8 weeks. K103N and Y181C, which confer nonnucleoside reverse transcriptase inhibitor (NNRTI) cross-resistance, were the predominant reverse transcriptase mutations. P236L, which confers DLV resistance but hypersensitivity to other NNRTIs, developed in <10% of isolates.

Adult↗
PubMed2004

Clinical implications of stopping nevirapine-based antiretroviral therapy: relative pharmacokinetics and avoidance of drug resistance.

OBJECTIVE: To determine the pharmacokinetics of cessation of nevirapine (NVP) in order to design clinical protocols which will reduce the risk of resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs). METHODS: In a case study, NNRTI genotypic resistance was demonstrated in a patient discontinuing therapy for toxicity. Subsequently, nine patients receiving NVP-containing antiretroviral regimens and stopping treatment were recruited. Patients were advised to continue the nucleoside analogue reverse transcriptase inhibitor (NRTI) backbone for 5 days following cessation of NVP. Plasma NVP concentrations were determined over 7-10 days after the last dose. HIV-1 reverse transcriptase genotyping was performed at viral load rebound (approximately day 21 following cessation) to detect mutations associated with reduced NNRTI sensitivity. RESULTS: The median predicted time for plasma NVP concentration to fall below the inhibitory concentration (IC)(50) of wild-type virus was 168 h (range 108-264 h). De novo genotypic mutations conferring resistance to NRTIs or NNRTIs were not demonstrated following cessation of therapy. CONCLUSIONS: The prolonged elimination half-life of NVP compared with NRTIs, which persists even after 20 weeks of therapy, raises concern over the development of NNRTI resistance if all three drugs are stopped together. Continuation of the NRTI backbone for a further 5 days, allowing the elimination of NVP, may avoid the development of drug resistance.

Anti-HIV Agents↗
PubMed2000

Saquinavir soft-gel capsule: an updated review of its use in the management of HIV infection.

UNLABELLED: Saquinavir is a potent and highly selective HIV protease inhibitor. Initially formulated as a hard-gel capsule (HGC), saquinavir was the first protease inhibitor available commercially for the treatment of patients with HIV infection. The limited oral bioavailability of saquinavir HGC has been improved significantly with the introduction of a soft-gel capsule (SGC) formulation. Saquinavir SGC displays greater than dose-proportional pharmacokinetics and mean area under the plasma concentration-time curve (AUC) values are 8- to 10-fold higher with saquinavir SGC 1200 mg 3 times daily than with the HGC formulation 600 mg 3 times daily, the recommended dosages of the 2 formulations. In combination with other protease inhibitors (particularly "low dose" ritonavir), the oral bioavailability of saquinavir (as either the HGC or SGC formulation) is markedly increased, allowing for reduced dosing frequency and/or dosage. The efficacy and tolerability of once- or twice-daily saquinavir SGC/"low dose" ritonavir combinations are currently being evaluated in patients with HIV infection. Data (up to 48 weeks) from noncomparative and comparative clinical trials evaluating saquinavir SGC-containing combination regimens in adult patients with HIV infection, support and strengthen the clinical efficacy profile of the drug that was demonstrated in initial trials. In antiretroviral therapy-naive and -experienced patients, saquinavir SGC combined with > or =2 nucleoside reverse transcriptase inhibitors (NRTIs), or nelfinavir, or nelfinavir plus 2 NRTIs or nonnucleoside reverse transcriptase inhibitors (NNRTIs), markedly improved immunological and virological surrogate markers (increased mean CD4+ cell counts and decreased mean plasma HIV RNA levels) of HIV infection. Saquinavir SGC demonstrated a trend to greater antiviral efficacy (measured by improvements in surrogate markers) than the HGC formulation (not statistically significant); a significantly greater proportion of patients treated with saquinavir SGC had plasma HIV RNA levels <400 copies/ml than patients receiving the HGC formulation. In the first direct comparison of 2 protease inhibitors, saquinavir SGC plus 2 NRTIs demonstrated similar antiviral efficacy to indinavir plus 2 NRTIs in patients with HIV infection (almost all of whom were antiretroviral therapy-naive); at 24 weeks, a significantly greater increase in CD4+ cell count from baseline was obtained in the saquinavir SGC group compared with the indinavir group, although this difference was not apparent at week 32. Triple therapy with saquinavir SGC plus 2 NRTIs was as effective as nelfinavir-containing triple therapy, or quadruple therapy (saquinavir SGC plus 2 NRTIs plus nelfinavir) in markedly suppressing HIV RNA levels in antiretroviral therapy-experienced or -naive patients. Saquinavir SGC is generally well tolerated. Gastrointestinal disturbances (generally nausea, diarrhoea, abdominal pain, vomiting and dyspepsia of moderate or greater intensity) are the most common adverse events associated with saquinavir SGC-containing therapy. In comparative trials, saquinavir SGC-containing therapy was as well tolerated as indinavir- and nelfinavir-containing therapy; although there were no statistical differences between treatment groups, the incidence of diarrhoea was lower in patients receiving saquinavir SGC compared with nelfinavir, saquinavir SGC plus nelfinavir (all combined with 2 NRTIs) or saquinavir SGC plus nelfinavir without additional therapy. Compared with the HGC formulation, saquinavir SGC appears to be associated with a higher overall incidence of adverse events. CONCLUSIONS: Clinical trial data have shown that as part of triple or quadruple combination therapy, saquinavir SGC is an effective and generally well tolerated protease inhibitor in antiretroviral therapy-naive or -experienced patients with HIV infection. (ABSTRACT TRUNCATED)

Animals↗
PubMed2000

Prevalence of genotypic and phenotypic resistance to anti-retroviral drugs in a cohort of therapy-naïve HIV-1 infected US military personnel.

OBJECTIVE: While transmission of drug-resistant HIV-1 has been reported, estimates of prevalence of resistance in drug-naïve populations are incomplete. We investigated the prevalence of genotypic mutations and phenotypic antiretroviral resistance in a cohort of HIV-1 infected U.S. military personnel prior to the institution of antiretroviral therapy. DESIGN: Cross-sectional cohort study. METHODS: Plasma was obtained from 114 recently HIV-1 infected subjects enrolled in an epidemiological study. Genotypic resistance was determined by consensus sequencing of a PCR product from the HIV-1 pol gene. Sequences were interpreted by a phenotypic-genotypic correlative database. Resistance phenotypes were determined by a recombinant virus cell culture assay. RESULTS: Genotypic mutations and phenotypic resistance were found at a higher than expected frequency. Resistance to non-nucleoside reverse transcriptase inhibitors was most common, with a prevalence of 15% of 95 subjects by genotype and 26% of 91 subjects by phenotype. Genotypic and phenotypic resistance respectively were found in 4% and 8% of subjects for nucleoside reverse transcriptase inhibitors and in 10% and 1% for protease inhibitors. One subject harbored virus with resistance to all three drug classes. CONCLUSIONS: A substantial frequency of resistance to antiretroviral drugs was identified in a therapy-naïve U.S. cohort. In most cases, the genotypic and phenotypic assays yielded similar results, although the genotypic assay could detect some protease inhibitor resistance-associated mutations in the absence of phenotypic resistance. These data suggest the need for optimization of treatment guidelines based on current estimates of the prevalence of drug resistance in HIV-1 seroconverters.

Adult↗
PubMed2002

Dioxolane guanosine, the active form of the prodrug diaminopurine dioxolane, is a potent inhibitor of drug-resistant HIV-1 isolates from patients for whom standard nucleoside therapy fails.

Amdoxovir ([-]-beta-D-2,6-diaminopurine dioxolane [DAPD]) is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against HIV-1. DAPD is deaminated in vivo by adenosine deaminase to (-)-beta-D-dioxolane guanosine (DXG), a highly active anti-HIV compound. The median 50% effective concentrations (EC 50 ) +/- SD (representing antiviral activity against a laboratory-derived HIV-1 isolate) for DAPD and DXG in peripheral blood mononuclear cells were 4.0 +/- 2.2 micromol/L and 0.25 +/- 0.17 micromol/L, respectively. The 50% cytotoxic dose (CC 50 ) of both DAPD and DXG was >500 micromol/L. Recombinant viruses and clinical isolates of HIV-1 from patients for whom NRTI therapy and/or nonnucleoside reverse transcriptase inhibitor (NNRTI) combination therapies failed remained susceptible to inhibition by DXG (less than fourfold change in EC 50). Similar analysis showed that recombinant viruses harboring mutations known to confer resistance to NRTIs (zidovudine, lamivudine, and abacavir) and NNRTIs (efavirenz and nevirapine) as well as the multidrug resistance-associated mutation Q151M and double codon insertions (SS and SG) were also susceptible to inhibition by DXG. Resistance to DXG was observed only in recombinant isolates containing the 65R and 151M double mutations. Phenotypic analysis of a site-directed mutant containing only the 151M mutation demonstrated moderate resistance to DXG (<10-fold change in EC 50). We also examined site-directed mutants containing only L74V or K65R, the characteristic resistance mutations for DXG. The L74V mutant remained susceptible to inhibition by DXG, and the K65R mutant demonstrated moderate resistance to DXG.

Antiviral Agents↗
PubMed1999

Effect of changing antiretroviral therapy on human immunodeficiency virus viral load: experience with fifty-four perinatally infected children.

BACKGROUND: Experience in adults has shown that combination therapy including HIV protease inhibitors (PI) can profoundly affect viral replication and slow progression of HIV-associated disease. Trials defining the influence of PI and combination therapies on long term outcome of HIV infection in children have not yet been completed. Experience with infants and children who were receiving routine care in an HIV specialty clinic was reviewed to characterize the effect of changes involving one, two or three antiretrovirals. METHODS: Clinical and laboratory findings of children in whom antiretroviral therapy was changed were retrospectively reviewed. Successful response was defined as a reduction of viral load of at least 0.7 log10 RNA copies/ml lasting for at least 3 months. Differences in characteristics and the character of the response associated with successful and unsuccessful changes were analyzed. RESULTS: Of the 72 changes in therapy that were made in 54 children, 29 resulted in a successful response. A change involving 3 antiretrovirals was more likely to produce a successful response than a change involving 1 agent (6 of 9 vs. 6 of 24; P < 0.04). Reduction of viral load by > 100-fold or to undetectable amounts occurred more frequently in children who responded to a regimen containing a PI than in children who responded to reverse transcriptase inhibitors (11 of 21 vs. 1 of 8; P=0.05). Furthermore successful responses associated with addition of a PI were associated with a greater reduction in viral load than those that involved reverse transcriptase inhibitors (1.63+/-0.60 vs. 0.99+/-0.12 log10; P=0.003). CONCLUSIONS: This experience suggests that changing antiretroviral therapy in HIV-infected children to regimens containing three drugs is more likely to result in a successful virologic outcome than changes in therapy involving one drug. This experience further supports the conclusion that including a PI as part of an antiretroviral regimen is more likely to result in a greater reduction in viral load in children.

Anti-HIV Agents↗
PubMed2004

Nevirapine in the treatment of HIV.

Nevirapine (Viramune, Boehringer Ingelheim Ltd) is the first marketed non-nucleoside reverse transcriptase inhibitor. As with any antiretroviral drug, nevirapine should always be used as part of a fully suppressive regimen. Clinical studies have shown that nevirapine-containing regimens may accomplish durable virological and immunological responses in approximately half of all antiretroviral-naive patients. It can also be successfully used as a component of salvage therapies and as a part of a strategy to simplify protease inhibitor-containing regimens. Nevirapine has a beneficial effect on the lipid profile in both treatment-naive and -experienced patients. Nevirapine also has an important role in preventing mother-to-child transmission of HIV. It is usually well-tolerated with rash and liver toxicity being the most frequently reported adverse events. Nevirapine interacts with cytochrome P450 enzymes both as a substrate and as an inducer. For this reason, therapeutic drug monitoring should be recommended whenever nevirapine is used with protease inhibitors, methadone (Methadose, Rosemont Pharmaceuticals Ltd), oral contraceptives, rifampicin (Rifadin, Aventis Pharma) and other potentially interacting drugs. Nevirapine-resistant mutations are common to the non-nucleoside reverse transcriptase inhibitor family and they include K103N, V106A, Y181C, Y188C and G190A. A better understanding of the nevirapine profile will certainly contribute to ensuring that its clinical application becomes more effective and beneficial.

Animals↗
PubMed2001

Riboflavin treatment of antiretroviral induced lactic acidosis and hepatic steatosis.

BACKGROUND: Antiretroviral induced lactic acidosis and hepatic steatosis is a rare syndrome caused by inhibition of deoxyribonucleic acid (DNA) polymerase gamma by the Nucleoside Reverse Transcriptase Inhibitor (NRTI) class of antiretrovirals. There have been recent reports of NRTI-induced lactic acidosis treated with high-dose riboflavin. INTERVENTION AND RESULTS: We report a case of NRTI lactic acidosis reversed with high-dose riboflavin. Treatment with 50 mg of riboflavin per day was initiated on hospital day 10 after the patient developed respiratory failure. Arterial lactate decreased from 11.9 mmol/dL to 2.1 mmol/dL. Despite lactic acidosis reversal the patient developed acute respiratory distress syndrome (ARDS) and expired. Autopsy confirmed extensive hepatic steatosis with no infectious agents identified. CONCLUSION: Nucleoside Reverse Transcriptase Inhibitor lactic acidosis will likely become more prevalent with the trend toward aggressive antiretroviral treatment. This report provides additional support for the efficacy of riboflavin treatment to reverse this serious complication of antiretroviral therapy. Clinicians should have a high index of suspicion for lactic acidosis in a patient on NRTIs and the medications should be stopped at the earliest sign of toxicity.

Acidosis, Lactic↗
PubMed2003

HIV-1 protease and reverse transcriptase mutation patterns responsible for discordances between genotypic drug resistance interpretation algorithms.

Several rules-based algorithms have been developed to interpret results of HIV-1 genotypic resistance tests. To assess the concordance of these algorithms and to identify sequences causing interalgorithm discordances, we applied four publicly available algorithms to the sequences of isolates from 2,045 individuals in northern California. Drug resistance interpretations were classified as S for susceptible, I for intermediate, and R for resistant. Of 30,675 interpretations (2,045 sequences x 15 drugs), 4.4% were completely discordant, with at least one algorithm assigning an S and another an R; 29.2% were partially discordant, with at least one algorithm assigning an S and another an I, or at least one algorithm assigning an I and another an R; and 66.4% displayed complete concordance, with all four algorithms assigning the same interpretation. Discordances between nucleoside reverse transcriptase inhibitor interpretations usually resulted from several simple, frequently occurring mutational patterns. Discordances between protease inhibitor interpretations resulted from a larger number of more complex mutation patterns. Discordances between nonnucleoside reverse transcriptase inhibitor interpretations were uncommon and resulted from a small number of individual drug resistance mutations. Determining the clinical significance of these mutation patterns responsible for interalgorithm discordances will improve interalgorithm concordance and the accuracy of genotypic resistance interpretation.

Algorithms↗
PubMed2005

Beyond efficacy: the impact of combination antiretroviral therapy on quality of life.

Combination antiretroviral therapy (ART) with two nucleoside reverse transcriptase inhibitors (NRTIs) plus a protease inhibitor (PI) significantly improved the prognosis of patients with HIV. Nevertheless, the usefulness of the first PIs was sometimes compromised by poor tolerability, high pill burden, frequent dosing, and food and fluid restrictions. Consequently, initial ART choices evolved toward simpler PI-sparing regimens incorporating non-nucleoside reverse transcriptase inhibitors or triple NRTIs. Because these PI-sparing alternatives also are imperfect, interest in PI-based approaches to initial therapy remains, especially in light of newer PIs that have a more favorable tolerability profile. The better safety and tolerability attributes of the newer PIs suggest that highly effective therapy can be administered while preserving patients' health-related quality of life. As long as the virologic activity of these newer PIs is comparable to that of existing options, differentiating features beyond efficacy are important in the choice of an appropriate treatment regimen for patients with HIV.

Antiretroviral Therapy, Highly Active↗
PubMed2003

[Problems in the management of HIV infection in clinical practice. Patients still on dual therapy 8 years after the introduction of HAART].

Eight years after the introduction of HAART as the standard therapy of HIV disease, around one fifth of treated patients of our cohort still rely on isolated dual nucleoside analogue administration, mostly due to an apparently effective treatment initiated with these last drugs before the HAART era, or severe intolerance to triple regimens based on protease inhibitors or non-nucleoside reverse transcriptase inhibitors, or patient's refusal of HAART. Three representative case reports are described, and their implications discussed on the ground of current guidelines of antiretroviral therapy and common clinical practice.

Adult↗
PubMed2007

Variability in non-nucleoside reverse transcriptase and protease inhibitors concentrations among HIV-infected adults in routine clinical practice.

AIMS: The objective of this study was to assess interindividual variability in plasma trough concentrations of non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI) among HIV-infected adults in an outpatient routine clinical practice setting. METHODS: The study included 117 patients who attended our clinic for routine outpatient blood tests and who were receiving antiretroviral therapy which included NNRTI or PI. Patients were not informed that drug concentrations were going to be assessed until blood sampling. The time of the last antiretroviral treatment intake and blood sampling were recorded. Drug concentrations were considered optimal if they were above the proposed minimum effective concentration. In addition, efavirenz, nevirapine and atazanavir concentrations were considered potentially toxic if they were higher than 4.0 mg l(-1), 6.0 mg l(-1), and 0.85 mg l(-1), respectively. RESULTS: Overall, interindividual variability in NNRTI and PI plasma concentrations was approximately 50%, and only 68.4% of the patients had drug concentrations within the proposed therapeutic range. Inappropriate adherence only explained 35% of subtherapeutic drug concentrations. CONCLUSION: Interindividual variability in trough concentrations of NNRTI and PI among HIV-infected adults is large in routine clinical practice, with drug concentrations being outside the therapeutic window in a significant proportion of patients. Therapeutic drug monitoring may be useful to guide antiretroviral therapy in clinical practice.

Adult↗
PubMed2001

The emergence of different resistance mechanisms toward nucleoside inhibitors is explained by the properties of the wild type HIV-1 reverse transcriptase.

Nucleoside reverse transcriptase inhibitors (NRTIs) represent one of the main drug families used against AIDS. Once incorporated in DNA, they act as chain terminators, due to the lack of a 3'-hydroxyl group. As for the other anti-human immunodeficiency virus type 1 drugs, their efficiency is limited by the emergence of resistant viral strains. Unexpectedly, previous studies indicated that resistance toward NRTIs is achieved via two distinct and generally exclusive mechanisms. Resistance mutations either decrease the efficiency of NRTIs incorporation or increase their excision from the extended primer. To understand the emergence of different resistance mechanisms toward a single inhibitor class, we compared the incorporation and the pyrophosphorolysis of several NRTIs using wild type reverse transcriptase (WT RT). We found that the efficiency of discrimination or excision by pyrophosphorolysis in the presence of nucleotides of a given NRTI is a key determinant in the emergence of one or the other resistance pathway. Indeed, our results suggest that the pathway by which RT become resistant toward a given NRTI can be predicted by studying the inhibition of WT RT, because the resistance mutations do not confer new properties to the mutant enzyme, but rather exacerbate pre-existing properties of the WT enzyme. They also help to understand the low cross-resistance toward d4T observed with the 3'-azido-3'-deoxythymidine (AZT or zidovudine)-resistant RT.

Acquired Immunodeficiency Syndrome↗
PubMed2004

The phenylmethylthiazolylthiourea nonnucleoside reverse transcriptase (RT) inhibitor MSK-076 selects for a resistance mutation in the active site of human immunodeficiency virus type 2 RT.

The phenylmethylthiazolylthiourea (PETT) derivative MSK-076 shows, besides high potency against human immunodeficiency virus type 1 (HIV-1), marked activity against HIV-2 (50% effective concentration, 0.63 microM) in cell culture. Time-of-addition experiments pointed to HIV-2 reverse transcriptase (RT) as the target of action of MSK-076. Recombinant HIV-2 RT was inhibited by MSK-076 at 23 microM. As was also found for HIV-1 RT, MSK-076 inhibited HIV-2 RT in a noncompetitive manner with respect to dGTP and poly(rC).oligo(dG) as the substrate and template-primer, respectively. MSK-076 selected for A101P and G112E mutations in HIV-2 RT and for K101E, Y181C, and G190R mutations in HIV-1 RT. The selected mutated strains of HIV-2 were fully resistant to MSK-076, and the mutant HIV-2 RT enzymes into which the A101P and/or G112E mutation was introduced by site-directed mutagenesis showed more than 50-fold resistance to MSK-076. Mapping of the resistance mutations to the HIV-2 RT structure ascertained that A101P is located at a position equivalent to the nonnucleoside RT inhibitor (NNRTI)-binding site of HIV-1 RT. G112E, however, is distal to the putative NNRTI-binding site in HIV-2 RT but close to the active site, implying a novel molecular mode of action and mechanism of resistance. Our findings have important implications for the development of new NNRTIs with pronounced activity against a wider range of lentiviruses.

Amino Acid Sequence↗
PubMed2006

Variability in non-nucleoside reverse transcriptase and protease inhibitor concentrations among HIV-infected adults in routine clinical practice.

AIMS: The objective of this study was to assess interindividual variability in trough concentrations of plasma of non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI) among HIV-infected adults in a routine outpatient setting. METHODS: One hundred and seventeen patients who attended our clinic for routine blood tests, and who were receiving antiretroviral therapy which included NNRTI or PI were studied. Patients were not informed that drug concentrations were going to be measured until blood sampling. The times of the last antiretroviral dose and of blood sampling were recorded. Drug concentrations were considered optimal if they were above the proposed minimum effective value. In addition, efavirenz, nevirapine and atazanavir concentrations were considered potentially toxic if they were > 4.0 mg l(-1), > 6.0 mg l(-1) and > 0.85 mg l(-1), respectively. RESULTS: Overall, interindividual variability of NNRTI and PI concentrations in plasma was approximately 50%, and only 68.4% of the patients had drug concentrations within the proposed therapeutic range. Poor adherence explained only 35% of subtherapeutic drug concentrations. CONCLUSION: Interindividual variability in trough concentrations of NNRTI and PI among HIV-infected adults is large in routine clinical practice, with drug concentrations being outside the therapeutic window in a significant proportion of patients. These findings provide further evidence that therapeutic drug monitoring may be useful to guide antiretroviral therapy in clinical practice.

Adult↗
PubMed2000

Effect of human immunodeficiency virus-1 protease inhibitors on the clearance of human herpesvirus 8 from blood of human immunodeficiency virus-1-infected patients.

The effect of human immunodeficiency virus-1 protease inhibitors on the frequency of human herpesvirus 8 DNA detection from peripheral blood of human immunodeficiency virus-positive persons was evaluated. Thirty-three human immunodeficiency virus-seropositive male patients were studied longitudinally. DNA from open reading frame 26 of the human herpesvirus 8 genome was amplified by the polymerase chain reaction from the CD45+ fraction of peripheral blood before and after the introduction of protease inhibitor therapy. Human herpesvirus 8 IgG status, CD4+ cell counts, and human immunodeficiency virus-1 plasma viral load were also assessed before and after therapy. When both reverse transcriptase inhibitor and protease inhibitor treatment were introduced at the same time, there was an increase in CD4+ T cell counts (P=0.0041), a decrease in human immunodeficiency virus plasma load (P=0.0584), and a decrease in the detection rate of human herpesvirus 8 DNA (P=0.0077). Introducing protease inhibitor to patients already receiving reverse transcriptase inhibitor treatment was associated with an increase in CD4+ T cell counts (P=0.0003), a decrease in human immunodeficiency virus plasma viral load (P=0.0911), and a decrease in the human herpesvirus 8 detection rate (P=0.0412). No significant changes in the titters of anti-human herpesvirus 8 IgG were observed. Treatment with human immunodeficiency virus-1 protease inhibitors is therefore associated with the clearance of human herpesvirus 8 DNA from peripheral blood of human immunodeficiency virus-infected patients. The concomitant decrease in the human immunodeficiency virus plasma load and increase in the peripheral CD4+ cell count suggest that an amelioration in the immune defect following reduction in the burden of human immunodeficiency virus-1 infection is responsible for the clearance of human herpesvirus 8 by protease inhibitors.

Adult↗
PubMed2006

Antiretroviral resistance in viral isolates from HIV-1-transmitting mothers and their infants.

OBJECTIVE: To characterize concordance of resistance mutations to antiretroviral drugs (ART) in mother-infant pairs. DESIGN: Case series of HIV-transmitting mothers and infants in the Women and Infants Transmission Study, where delivery occurred between April 1994 and December 1999. METHODS: Reverse transcriptase and protease genes were sequenced in stored viral isolates from 32 mother-infant pairs. Mutations were coded as "pure mutants" where only mutant virus was detected or as "mixtures" where a mixed mutant/wild-type population was identified. ART resistance mutations were compared for concordance between mothers and their infants. RESULTS: Maternal mutations associated with resistance to nucleoside reverse transcriptase inhibitor (NRTI) and minor protease inhibitor (PI) drugs were typically concordant with that of infant, while those associated with non-nucleoside reverse transcriptase inhibitors (NNRTI) and major PI drugs were not. Of five NRTI-associated maternal mutations observed, three pure mutants corresponded with mutant in the infant, while two wild-type-predominant mixtures corresponded with infant wild type. The only NNRTI-associated mutation observed, K103N, was not transmitted, nor were the two major PI-associated mutations, L90M and V82I/V. Transmission of minor PI-associated mutations was consistent with the sole observed or dominant variant for 20 of 21 mutations. CONCLUSIONS: For NRTI- and minor PI-associated mutations, transmission was consistent with relative quantity of variants in maternal virus. However, where NNRTI- and major PI-associated mutations were present in three cases, they were not transmitted, even where only mutant virus was detectable in maternal isolates. This is consistent with evidence of loss of transmission with resistance to NNRTI and PI drugs.

Anti-HIV Agents↗