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Biomedical subjects

Praphan Phanuphak

Publications and source records attributed to Praphan Phanuphak.

At least 19 recordsLinked to original sources
PubMed2006

Effects of highly active antiretroviral therapy (HAART) on psychomotor performance in children with HIV disease.

OBJECTIVE: This study assesses the effects of HAART on psychomotor performance of symptomatic HIV-infected children. It is one of the first studies to look at neurobehavioral functioning in children infected with HIV in resource-limited countries. DESIGN: A longitudinal pilot study of vertically HIV-infected children at the HIV Netherlands Australia Thailand Research Collaboration Center in Bangkok, Thailand. METHODS: A total of 34 children participated in the study of whom 16 had never received antiretroviral (ARV) therapy and were about to start HAART (Newly treated children), 7 did not receive antiretroviral therapy (Untreated children) and 11 had been treated with HAART for more than one year (HAART experienced children). All children were administered 4 psychomotor tasks at baseline and after 4 months. The Newly treated and the Untreated children were also evaluated after 12 months. RESULTS: In general, the children performed similarly on all psychomotor tasks at baseline. After 12 months of HAART, there was a significant increase in CD4% in the Newly treated group. Overall, psychomotor performance did not change at the 4-month evaluation in all groups. At the 12-month evaluation psychomotor performance had deteriorated substantially on all tasks in both the Newly treated and the Untreated children. CONCLUSIONS: There was no significant difference in psychomotor functioning between children newly treated, previously treated and untreated with HAART over the course of one year. Psychomotor performance deteriorated after 12 months of HAART, which provides important indications concerning the lack of benefits of HAART on psychomotor functions in children despite immunologic reconstitution. Further research with larger sample sizes is needed to confirm these findings.

Analysis of Variance↗
PubMed2006

Viral decay dynamics in HIV-infected patients receiving ritonavir-boosted saquinavir and efavirenz with or without enfuvirtide: a randomized, controlled trial (HIV-NAT 012).

The availability of enfuvirtide enables assessment of whether human immunodeficiency virus (HIV) decay can be enhanced by targeting reverse transcriptase, protease, and fusion. We performed a 12-week study of 22 patients randomized to receive ritonavir-boosted saquinavir and efavirenz with (the 3-target arm) or without (the 2-target arm) enfuvirtide. We observed no difference in the mean+/-SD elimination-rate constant for overall decay (0.142+/-0.040 per day and 0.128 +/- 0.033 per day in the 2- and 3-target arms, respectively; P>.1) or for modeled first-phase decay rate (-0.62+/-0.34 per day and -0.51+/-0.16 per day; P>.1). Antiretroviral therapy that inhibits HIV reverse transcriptase and protease exerts potent antiviral effects that might not be augmented by the addition of an HIV fusion inhibitor.

Alkynes↗
PubMed2006

CD4-guided scheduled treatment interruptions compared with continuous therapy for patients infected with HIV-1: results of the Staccato randomised trial.

BACKGROUND: Stopping antiretroviral therapy in patients with HIV-1 infection can reduce costs and side-effects, but carries the risk of increased immune suppression and emergence of resistance. METHODS: 430 patients with CD4-positive T-lymphocyte (CD4) counts greater than 350 cells per muL, and viral load less than 50 copies per mL were randomised to continued therapy (n=146) or scheduled treatment interruptions (n=284). Median time on randomised treatment was 21.9 months (range 16.4-25.3). Primary endpoints were proportion of patients with viral load less than 50 copies per mL at the end of the trial, and amount of drugs used. Analysis was intention-to-treat. This study is registered at ClinicalTrials.gov with the identifier NCT00113126. FINDINGS: Drug savings in the scheduled treatment interruption group, compared with continuous treatment, amounted to 61.5%. 257 of 284 (90.5%) patients in the scheduled treatment interruption group reached a viral load less than 50 copies per mL, compared with 134 of 146 (91.8%) in the continued treatment group (difference 1.3%, 95% CI-4.3 to 6.9, p=0.90). No AIDS-defining events occurred. Diarrhoea and neuropathy were more frequent with continuous treatment; candidiasis was more frequent with scheduled treatment interruption. Ten patients (2.3%) had resistance mutations, with no significant differences between groups. INTERPRETATION: Drug savings with scheduled treatment interruption were substantial, and no evidence of increased treatment resistance emerged. Treatment-related adverse events were more frequent with continuous treatment, but low CD4 counts and minor manifestations of HIV infection were more frequent with scheduled treatment interruption.

Adolescent↗
PubMed2006

Changes in body composition and mitochondrial nucleic acid content in patients switched from failed nucleoside analogue therapy to ritonavir-boosted indinavir and efavirenz.

BACKGROUND: Body composition changes complicate antiretroviral therapy. Improvements in lipoatrophy after a switch in nucleoside reverse-transcriptase inhibitors (NRTIs) have been demonstrated. We investigated 60 patients switching from failed NRTIs to ritonavir-boosted indinavir and efavirenz. METHODS: Body composition (assessed by dual-energy x-ray absorptiometry scan and by single-slice computed tomography of the abdomen through the level of the fourth lumbar vertebra [L4] and the mid-right thigh) and fasted metabolics were measured at the baseline time-point at switch and at weeks 48 and 96 thereafter. Mitochondrial DNA and RNA were extracted from right-thigh subcutaneous fat and peripheral-blood mononuclear cells (PBMCs) at weeks 0 and 48. The primary end point was the change in mean limb fat over 48 weeks. RESULTS: At week 96, we observed increases in mean (standard deviation [SD]) limb fat (+620 [974] g; P=.003), L4 subcutaneous adipose tissue (+20 [35] cm(2); P<.001), mid-thigh subcutaneous adipose tissue (+5 [10] cm(2); P<.001), and L4 visceral adipose tissue (+11 [34] cm(2); P=.01), but we also observed reduced lean limb mass (-831 [1,100] g; P=.3). Mean (SD) mtDNA content in subcutaneous fat and in PBMCs increased (+109 [274] and +45 [100] copies/cell, respectively). Improved virological control or immune recovery did not explain the results. Triglyceride, total cholesterol, estimated low-density lipoprotein cholesterol, ratio of total cholesterol to high-density lipoprotein cholesterol, and blood glucose levels deteriorated (i.e., had increased by 206%, 67%, 58%, 19%, and 6%, respectively, at week 96). CONCLUSIONS: This regimen was associated with statistically significant but clinically modest increases in peripheral fat, visceral fat, and mitochondrial nucleic acid content. A predominantly adverse metabolic profile developed.

Absorptiometry, Photon↗
PubMed2006

Efficacy and tolerability of 10-day monotherapy with apricitabine in antiretroviral-naive, HIV-infected patients.

OBJECTIVE: Apricitabine (formerly AVX754 and SPD754) is a deoxycytidine analogue nucleoside reverse transcriptase inhibitor in clinical development for patients with HIV disease. This study evaluated the antiretroviral efficacy, tolerability and safety of apricitabine monotherapy, administered for 10 days in antiretroviral-naive, HIV-1 infected adults. METHODS: Adult patients (> or = 18 years) with HIV infection (CD4 count > or = 250 cells/microl; plasma HIV-1 RNA level 5000-100 000 copies/ml) were randomized to 10 days' double-blind oral therapy with placebo or apricitabine 400 mg/day, 800 mg/day, 1200 mg/day, or 1600 mg/day. RESULTS: At 7 days, all apricitabine doses produced statistically significant log10 reductions in plasma HIV RNA levels from baseline relative to placebo (n = 13; P < 0.0001), as follows: -1.16 (400 mg; n = 11), -1.28 (800 mg; n = 12), -1.44 (1200 mg; n = 14), -1.30 (1600 mg; n = 13). After 10 days, the log10 viral load reductions with apricitabine 1200 mg (-1.65; P = 0.01) and 1600 mg/day (-1.58; P = 0.04) were significantly greater than that with the 400-mg dose (-1.18). No clinically relevant changes were observed in CD4 or CD8 cell indices. Apricitabine was well tolerated and showed no tendency to select any particular resistance mutation. CONCLUSION: Apricitabine monotherapy showed promising antiretroviral efficacy, good tolerability and a low propensity for resistance selection in antiretroviral-naive HIV-infected patients treated for 10 days. These results warrant further evaluation of the long-term clinical efficacy and tolerability of apricitabine.

Administration, Oral↗
PubMed2006

The use of pharmacokinetically guided indinavir dose reductions in the management of indinavir-associated renal toxicity.

OBJECTIVES: Indinavir is associated with nephrotoxicity. Therapeutic drug monitoring of indinavir improves clinical outcome, but there is little data regarding therapeutic drug monitoring for patients with established indinavir-associated renal impairment. We prospectively studied the use of therapeutic drug monitoring in patients with virological success but established nephrotoxicity on an indinavir-containing regimen. METHODS: We measured indinavir C(trough)/C(2h), serum creatinine, pyuria, blood pressure (BP), weight and HIV RNA. The major endpoint of interest was the number of patients achieving a normal creatinine level 20 weeks following final indinavir dose adjustment. Primary analysis was by intention to treat (ITT). RESULTS: A total of 35 patients were enrolled; mean (SD) age 40.3 (5.8) years; mean (SD) BMI 21.5 (2.8) kg/m(2). At baseline 6/35 (17%) had a serum creatinine concentration within normal limits, but were offered enrolment because of previous nephrotoxicity (nephrolithiasis and/or abnormal serum creatinine), and a screening pharmacokinetic profile associated with increased nephrotoxicity risk. By ITT analysis 11/35 (31%) had normal creatinine at study end (P = 0.18). Of the 29 patients with abnormal creatinine at baseline, 7/29 (24.1%) had normal creatinine at study end (P = 0.016). Patients had a median (IQR) indinavir per dose adjustment over the study of 400 (400-800) mg. We observed improvements in estimated creatinine clearance, pyuria, resting BP and indinavir pharmacokinetic profile. HIV RNA control was maintained with continued immune recovery despite lower indinavir doses. CONCLUSIONS: Patients experiencing nephrotoxicity on an indinavir-containing regimen were safely maintained on indinavir by means of therapeutic drug monitoring. Parameters of renal function improved but did not return to baseline values, at least in the short-term.

Adult↗
PubMed2006

Inconsistent condom use with steady and casual partners and associated factors among sexually-active men who have sex with men in Bangkok, Thailand.

HIV/STD risk behavior has not been examined in community samples of men who have sex with men (MSM) in Thailand. The sexually-active sample (n=927) was recruited from bars, saunas, and parks; 20% identified as bisexual and 17% tested HIV-positive. Inconsistent (<100%) condom use was reported by 45% of those with steady partners and 21% of those with casual partners in the prior three months. 21% had heard of effective HIV treatments (n=194), among whom 44% believed HIV was less serious and 36% said their risk behavior had increased after hearing about the treatments. In multivariate analysis, HIV-positive status, gay-identification, getting most HIV information from the radio, believing HIV can be transmitted by mosquito bite, and concern about acquiring an STD were associated with inconsistent condom use during anal sex; slightly older age (25-29 vs. 18-24 years) was associated with more consistent condom use. HIV/STD risk-reduction strategies for MSM in Bangkok should clearly state sexual risk to individuals in this population.

Adolescent↗
PubMed2006

Monitoring the toxicity of antiretroviral therapy in resource limited settings: a prospective clinical trial cohort in Thailand.

BACKGROUND: One of the many challenges which come together with the implementation of antiretroviral therapy (ART) in settings with limited resources is the monitoring of toxicity. This monitoring increases costs of ART and strains resources. We therefore investigated the necessity for laboratory toxicity monitoring of ART in Thailand. DESIGN, METHODS AND PARTICIPANTS: A prospective Thai cohort of 417 HIV-infected patients were enrolled in randomized clinical trials investigating ART. Time-dependent occurrence of grade III/IV abnormal laboratory values as defined by the AIDS Clinical Trial Group was analysed. RESULTS: During a median observation period of 3.7 years (2.4-4.3) 142 grade III/IV toxicities occurred in 101 (24.2%) patients. Hepatic toxicity (n = 33, 7.9%), hypercholesterolaemia (n = 57, 13.7%), hypertriglyceridaemia (n = 26, 6.2%), anaemia (n = 16, 3.8%) and low platelet counts (n = 8, 1.9%) were frequently observed. Anaemia and low platelets occurred early and during the first 2 years of ART. Hepatic toxicity was seen early and throughout the observation period. Hypertriglyceridaemia and hypercholesterolaemia occurred throughout the observation period, and increased over time. Hypercreatininaemia and hyperglycaemia occurred once after 120 and 132 weeks. ART was changed or interrupted for grade III/IV hepatic toxicity, anaemia and hyperglycaemia only. The incidence rate for grade III/IV toxicity was between 5.56 (95% CI, 6.76-18.02) for low platelet counts and 41.18 (31.77-53.39) per 1000 patient years for hypercholesterolaemia. Antiretrovirals used were zidovudine, stavudine, lamivudine, zalcitabine, didanosine, efavirenz, saquinavir, ritonavir and indinavir. CONCLUSIONS: Grade III/IV toxicity is frequently observed in Thai patients treated with ART. The simple and inexpensive monitoring of ALT and haemoglobin could prevent most serious short-term toxicity. Long-term toxicity can be addressed with a yearly monitoring of triglycerides, cholesterol, glucose and creatinine if nephrotoxic drugs are used.

Adult↗
PubMed2006

Relationship between hyperbilirubinaemia and UDP-glucuronosyltransferase 1A1 (UGT1A1) polymorphism in adult HIV-infected Thai patients treated with indinavir.

OBJECTIVES: To investigate the association between the UGT1A1*6 (G71R) and UGT1A1*28 (promoter (TA)7-repeat) genotypes and hyperbilirubinaemia in Thai patients treated with indinavir, and characterize the inhibition of human UGTs by indinavir in vitro. METHODS: Ninety-six Thai HIV patients receiving indinavir, 800 mg t.i.d. or 800 mg b.i.d. "boosted" with ritonavir (100 mg b.i.d.), had serum bilirubin levels measured to 24 weeks post-treatment and were genotyped for UGT1A1*6 and UGT1A1*28. The inhibition selectivity and kinetics of indinavir were determined using a panel of recombinant human UGTs. RESULTS: UGT1A1*6 and UGT1A1*28 frequencies in the Thai patients were 10.4% and 15.6%, respectively. Total, conjugated (direct) and unconjugated (indirect) serum bilirubin concentrations increased significantly at 24 weeks of indinavir treatment for all four genotypes, with a trend towards higher levels depending on the number of UGT1A1 mutant alleles; *6/*28 > *6 > *28 > reference. The hazards ratio (HR) for serious hyperbilirubinaemia (total bilirubin > 2.5 mg/dl) at week 24 was statistically significant only in those patients carrying the UGT1A1*6 (HR 2.87) and UGT1A1*6/*28 (HR 11.42) genotypes. The Ki values for indinavir inhibition of UGT1A1 and UGT1A1*6 were 4.1 and 10.7 mumol/l respectively. However, indinavir was also shown to inhibit other human UGTs, notably UGT1A3 and UGT1A7. CONCLUSIONS: In contrast to Caucasian HIV-infected patients treated with indinavir, the promoter polymorphism (UGT1A1*28) is of less significance than the coding region (UGT1A1*6) mutation as a risk factor for hyperbilirubinaemia. The Ki values determined for indinavir inhibition of UGT1A1 are consistent with an interaction in vivo, with an additive effect in patients with already impaired bilirubin glucuronidation activity.

Adult↗
PubMed2006

Discordances between interpretation algorithms for genotypic resistance to protease and reverse transcriptase inhibitors of human immunodeficiency virus are subtype dependent.

The major limitation of drug resistance genotyping for human immunodeficiency virus remains the interpretation of the results. We evaluated the concordance in predicting therapy response between four different interpretation algorithms (Rega 6.3, HIVDB-08/04, ANRS [07/04], and VGI 8.0). Sequences were gathered through a worldwide effort to establish a database of non-B subtype sequences, and demographic and clinical information about the patients was gathered. The most concordant results were found for nonnucleoside reverse transcriptase (RT) inhibitors (93%), followed by protease inhibitors (84%) and nucleoside RT inhibitor (NRTIs) (76%). For therapy-naive patients, for nelfinavir, especially for subtypes C and G, the discordances were driven mainly by the protease (PRO) mutational pattern 82I/V + 63P + 36I/V for subtype C and 82I + 63P + 36I + 20I for subtype G. Subtype F displayed more discordances for ritonavir in untreated patients due to the combined presence of PRO 20R and 10I/V. In therapy-experienced patients, subtype G displayed a lot of discordances for saquinavir and indinavir due to mutational patterns involving PRO 90 M and 82I. Subtype F had more discordance for nelfinavir attributable to the presence of PRO 88S and 82A + 54V. For the NRTIs lamivudine and emtricitabine, CRF01_AE had more discordances than subtype B due to the presence of RT mutational patterns 65R + 115 M and 118I + 215Y, respectively. Overall, the different algorithms agreed well on the level of resistance scored, but some of the discordances could be attributed to specific (subtype-dependent) combinations of mutations. It is not yet known whether therapy response is subtype dependent, but the advice given to clinicians based on a genotypic interpretation algorithm differs according to the subtype.

Algorithms↗
PubMed2006

Calypte AWARE HIV-1/2 OMT antibody test using oral fluid: special challenges of rapid HIV testing in the developing world.

The testing and counseling of persons at risk for infection with HIV and their subsequent treatment remains the primary tool to curb worldwide transmission of the virus. Rapid HIV tests address the need in the developing world for accurate, easy-to-use tests that do not require laboratory equipment or highly trained professionals for implementation or refrigeration for storage. Calypte Biomedical has recently developed the Calypte AWARE HIV-1/2 OMT antibody test using oral fluid samples. This test has demonstrated high sensitivity and specificity for specimens collected in target areas where increased testing is needed. The inexpensive dipstick format in combination with the use of an alternative fluid to blood provides an improved testing procedure for areas with limited resources.

AIDS Serodiagnosis↗
PubMed2006

Boosted versus unboosted indinavir with zidovudine and lamivudine in nucleoside pre-treated patients: a randomized, open-label trial with 112 weeks of follow-up (HIV-NAT 005).

INTRODUCTION: The use of HIV protease inhibitors (PIs) in a ritonavir (RTV)-boosted form is now common. However, randomized data comparing boosted with unboosted PI strategies are scarce. METHODS: This randomized, open-label trial compared indinavir (IDV) 800 mg three times daily with IDV/RTV 800/100 mg twice daily, both given with zidovudine (AZT)/lamivudine (3TC) twice daily in individuals with at least 3 months previous AZT experience. The primary endpoint was the time-weighted average change in HIV RNA from baseline. Designed as a 48-week study, follow-up continued until week 112. Primary analysis is by intention to treat. RESULTS: One hundred and three patients commenced therapy and are included in the analysis. Patients had a median of 29 months past nucleoside reverse transcriptase inhibitor (NRTI) exposure. Baseline median (interquartile range) log10 HIV RNA was 4.0 (3.3-4.5) and CD4+ T-cell count 166 (40-323) cells/microl. After 112-weeks of study there was no significant difference observed between arms in the mean (SD) change in time-weighted average HIV RNA from baseline (-1.6 [1.1] HIV RNA copies/week/ml three times daily arm; -1.4 [1.1] HIV RNA copies/week/ml twice daily arm; P = 0.3). Both arms were associated with substantial toxicity expressed as serious adverse events and study drug interruptions. The twice daily arm experienced greater dyslipidaemia. Mean (SD) changes in time-weighted CD4+ T-cell count from baseline were similar [88 (84) cells/week/microl three times daily arm; 70 [109] cells/week/microl twice daily arm; P = 0.3). CONCLUSIONS: RTV-boosted IDV 800/100 mg twice daily demonstrated comparable efficacy to unboosted IDV 800 mg three times daily dosing. Both regimens were associated with substantial toxicity. Use of lower doses of RTV-boosted IDV may result in better tolerability without loss of efficacy and warrant further research.

Adult↗
PubMed2006

High prevalence of indinavir-associated renal complications in Thai HIV-infected patients.

BACKGROUND: Indinavir (IDV) is the protease inhibitor (PI) used most often in resource-limited countries. The present study aimed to determine the prevalence of IDV-associated renal complications as well as their clinical characteristics. MATERIAL AND METHOD: The authors reviewed all patients participating in cohorts of indinavir-containing regimens at the HIV-NAT research center during the period of indinavir treatment. Patients who had pre-existing renal diseases were excluded. Renal toxicities included presence of urologic symptoms, nephrolithiasis, abnormal urine sediments, crystalluria and loss of renal function. Radiological studies of KUB system were reviewed as well. RESULTS: Two-hundred and four patients treated with IDV were included. Median (IQR) follow up period was 216 (150-312) weeks. One hundred and eighty patients were treated with ritonavir-boosted regimens at some point, and 24 patients were treated only with unboosted regimens. Leukocyturia (51.9%) was the most common finding of IDV-associated renal complications. Thirty-five percent of patients had urologic symptoms such as flank pain or dysuria. Almost half of the patients had significant loss of renal function that was associated with prolonged use of IDV The most common radiological finding was nephrolithiasis. Less common, but of greater clinical importance, are nephrocalcinosis or renal atrophy. CONCLUSION: A high prevalence of IRC was found in Thai HIV-infected patients. As long as no other cost-effective boosted PI regimens are available, strategies to prevent irreversible loss of renal function are warranted.

Adult↗
PubMed2005

Interindividual variability of once-daily ritonavir boosted saquinavir pharmacokinetics in Thai and UK patients.

OBJECTIVES: Differential exposure to saquinavir/ritonavir may lead to therapy failure. The objective was to identify factors that influence variability of saquinavir/ritonavir plasma concentrations. METHODS: Saquinavir/ritonavir data, dosed as 1600/100 mg once daily, from three separate pharmacokinetic studies, in 45 patients from Thailand and the UK, were pooled. Pharmacokinetic parameters were based on non-compartmental analysis. Univariate analysis was performed with saquinavir as the dependent variable, and ritonavir area under the curve (AUC), gender, body weight, body mass index (BMI) and study site as independent variables. Variables with a P value <0.10 were included in a multivariate linear regression analysis. RESULTS: Higher saquinavir AUCs, maximum concentrations (Cmax) and minimum concentrations (Cmin) were seen in Thai patients than in UK patients. Univariate analysis showed associations between body weight, gender, study site and ritonavir AUC and saquinavir AUC (P < 0.05), whereas BMI (P = 0.13) did not. In the multivariate analysis, ritonavir AUC (P = 0.0001) and study site (P = 0.0021) were significantly related to saquinavir AUC (R2 = 0.50). CONCLUSIONS: The ritonavir AUC and study site appeared to be related to exposure of saquinavir. Study site should be viewed as the total of country- and study-specific differences--such as differences in lifestyle, environment, genetic background and dietary composition--between the analysed studies.

Adult↗
PubMed2005

Highly active antiretroviral therapy (HAART) retreatment in patients on CD4-guided therapy achieved similar virologic suppression compared with patients on continuous HAART: the HIV Netherlands Australia Thailand Research Collaboration 001.4 study.

OBJECTIVE: To assess the safety of 2 intermittent treatment strategies compared with continuous therapy for patients with virologic suppression on highly active antiretroviral therapy (HAART) at baseline. DESIGN: Seventy-four nucleoside reverse transcriptase inhibitor (NRTI) and protease inhibitor (PI) pretreated patients with an HIV RNA level <50 copies at screening were randomized to continuous treatment, CD4-guided treatment, or week-on-week-off treatment with 2 NRTIs plus 1600 mg/100 mg of saquinavir/ritonavir once daily. At week 96 (end of the randomized phase of the study), all patients were given continuous HAART for 12 weeks to week 108. Primary outcomes were the proportion of patients with a CD4 count >350 cells/microL and HIV RNA level <400 copies/mL at week 108. METHODS: Patients were followed up every 12 weeks for CD4 count, HIV RNA level, and clinical and laboratory toxicities. In the CD4-guided arm, treatment was stopped and restarted using a CD4 count threshold (above or below 350 cells/microL or reduction of 30%). RESULTS: Seventy-four patients were enrolled with a median CD4 count of 644 cells/microL before the structured treatment interruption (STI). The week-on-week-off arm (n=26) was discontinued at week 72 because of high rates (46%) of HIV RNA rebound above 50 copies/mL. In the continuous arm, 25 (100%) of 25 patients and 24 (96%) of 25 patients had an HIV RNA level <400 copies/mL and <50 copies/mL, respectively, at week 108, and 96% had a CD4 count above 350 cells/microL, with a median CD4 count of 661 cells/microL. Patients in the CD4-guided arm had a significantly lower median CD4 count (489 cells/microL) than the patients in the continuous arm (P=0.03), but all had a CD4 count above 350 cells/microL and 1 had a new HIV-related illness. At week 108, 21 (91%) of 23 patients and 13 (57%) of 23 patients had an HIV RNA level <400 copies/mL and <50 copies/mL, respectively. Those who did not achieve an HIV RNA level <50 copies/mL had a higher HIV RNA load before retreatment, and 4 of 5 patients subsequently achieved viral suppression after an additional 12 weeks of HAART (week 120). Therefore, 17 (94%) of 18 evaluable CD4-guided arm patients achieved viral suppression after retreatment. Antiretroviral (ARV) side effects were similar in all arms. CD4-guided treatment had a 54% ARV cost savings. CONCLUSIONS: This pilot study suggests that CD4-guided HAART is a well-tolerated and cost-saving treatment strategy for patients with high pre-ARV and pre-STI CD4 counts. Week-on-week-off treatment had a high virologic failure rate and was discontinued. The HIV RNA suppression rate was similar in patients treated with continuous HAART and in those retreated with 12 to 24 weeks of HAART after CD4-guided therapy.

Adult↗
PubMed2005

Impact of HIV-1 subtype and antiretroviral therapy on protease and reverse transcriptase genotype: results of a global collaboration.

BACKGROUND: The genetic differences among HIV-1 subtypes may be critical to clinical management and drug resistance surveillance as antiretroviral treatment is expanded to regions of the world where diverse non-subtype-B viruses predominate. METHODS AND FINDINGS: To assess the impact of HIV-1 subtype and antiretroviral treatment on the distribution of mutations in protease and reverse transcriptase, a binomial response model using subtype and treatment as explanatory variables was used to analyze a large compiled dataset of non-subtype-B HIV-1 sequences. Non-subtype-B sequences from 3,686 persons with well characterized antiretroviral treatment histories were analyzed in comparison to subtype B sequences from 4,769 persons. The non-subtype-B sequences included 461 with subtype A, 1,185 with C, 331 with D, 245 with F, 293 with G, 513 with CRF01_AE, and 618 with CRF02_AG. Each of the 55 known subtype B drug-resistance mutations occurred in at least one non-B isolate, and 44 (80%) of these mutations were significantly associated with antiretroviral treatment in at least one non-B subtype. Conversely, of 67 mutations found to be associated with antiretroviral therapy in at least one non-B subtype, 61 were also associated with antiretroviral therapy in subtype B isolates. CONCLUSION: Global surveillance and genotypic assessment of drug resistance should focus primarily on the known subtype B drug-resistance mutations.

Amino Acid Sequence↗