Biomedical subjects

Janaki Amin

Publications and source records attributed to Janaki Amin.

16 recordsLinked to original sources

PubMed2006

Causes of death after diagnosis of hepatitis B or hepatitis C infection: a large community-based linkage study.

BACKGROUND: Hepatitis B and hepatitis C virus infections are common causes of death related to liver disease. In this large study, we aimed to investigate all cause mortality of the viruses in a community-based setting. METHODS: In the study population, 39,109 people had hepatitis B, 75,834 had hepatitis C, and 2604 had hepatitis B and hepatitis C co-infection, notified to the New South Wales state health department, Australia, between 1990 and 2002. Their data were probabilistically linked to the National Death Index. Standardised mortality ratios for all causes of death were calculated and adjusted for age, sex, and calendar year. RESULTS: The number of deaths identified by the linkage were 1233 (3.2%) for hepatitis B, 4008 (5.3)% for hepatitis C, and 186 (7.1)% for hepatitis B and C co-infection. Raised risk of liver-related death (standardised mortality ratios 12.2, 95% CI 10.7-13.9; 16.8, 15.4-18.3, and 32.9, 23.1-46.7, for hepatitis B, hepatitis C, and hepatitis B and C co-infected patients, respectively) and drug-induced death (1.4, 1.0-2.0; 19.3, 18.1-20.5; and 24.7, 18.2-33.5, respectively) were detected. In people with hepatitis C, raised risk of dying from drug-related causes was significantly greater than from liver-related causes (p=0.012), with the greatest excess risk in women aged 15-24 years (56.9, 39.2-79.9). INTERPRETATION: All groups had increased risk of liver-related death compared with the standard population, with the greatest excess in people diagnosed with hepatitis B and hepatitis C co-infection. Our data highlight that young people with hepatitis C and with co-infection face a higher mortality risk from continued drug use than from their infection, whereas the main cause of hepatitis B death was liver related.

Adult↗

PubMed2006

Cancer incidence in people with hepatitis B or C infection: a large community-based linkage study.

BACKGROUND/AIMS: Risks of hepatocellular carcinoma (HCC) following hepatitis B and/or hepatitis C virus (HBV/HCV) infection are well known, those for other cancers are less well understood. The aim was to quantify the risk of cancers among persons diagnosed with HBV/HCV infections. METHODS: The data from a cohort of 39109 HBV, 75834 HCV, and 2604 HBV/HCV co-infected persons notified to the State health department, 1990-2002, were probabilistically linked to the Cancer Registry and standardised incidence ratios (SIRs) for cancer were calculated. RESULTS: The match rate for any cancer was 2.7%, 2.3% and 3.3% for HBV, HCV and HBV/HCV co-infected notifications. SIRs for HCC were 30.6 (95% CI 25.7-36.5), 22.7 (95% CI 19.1-26.5) and 30.3 (95% CI 13.6-67.5), respectively. Increased risk was detected for Burkitt's lymphoma and HBV (SIR 12.9, 95% CI 5.4-30.9) and immunoproliferative malignancies following HCV (SIR 5.6, 95% CI 1.8-17.5). CONCLUSIONS: The risk of HCC in the infected cohort was 20-30 times greater than in the uninfected population with SIRs two to three times greater than those for the other HBV/HCV infection associated cancers. The modest though significant risk of immunoproliferative malignancies associated with HCV infection is consistent with recent findings.

Adult↗

PubMed2006

Measurement of serum levels of macrophage inhibitory cytokine 1 combined with prostate-specific antigen improves prostate cancer diagnosis.

PURPOSE: Current serum testing for the detection of prostate cancer (PCa) lacks specificity. On diagnosis, the optimal therapeutic pathway is not clear and tools for adequate risk assessment of localized PCa progression are not available. This leads to a significant number of men having unnecessary diagnostic biopsies and surgery. A search for novel tumor markers identified macrophage inhibitory cytokine 1 (MIC-1) as a potentially useful marker. Follow-up studies revealed MIC-1 overexpression in local and metastatic PCa whereas peritumoral interstitial staining for MIC-1 identified lower-grade tumors destined for recurrence. Consequently, we sought to assess serum MIC-1 measurement as a diagnostic tool. EXPERIMENTAL DESIGN: Using immunoassay determination of serum MIC-1 concentration in 1,000 men, 538 of whom had PCa, we defined the relationship of MIC-1 to disease variables. A diagnostic algorithm (MIC-PSA score) based on serum levels of MIC-1, total serum prostate-specific antigen, and percentage of free prostate-specific antigen was developed. RESULTS: Serum MIC-1 was found to be an independent predictor of the presence of PCa and tumors with a Gleason sum > or =7. We validated the MIC-PSA score in a separate population and showed an improved specificity for diagnostic blood testing for PCa over percentage of free prostate-specific antigen, potentially reducing unnecessary biopsies by 27%. CONCLUSIONS: Serum MIC-1 is an independent marker of the presence of PCa and tumors with a Gleason sum of > or =7. The use of serum MIC-1 significantly increases diagnostic specificity and may be a future tool in the management of PCa.

Biomarkers, Tumor↗

PubMed2006

Nonnucleoside reverse transcriptase inhibitor fold change or plasma concentration as a predictor of virological response over 48 weeks in highly treatment experienced HIV-positive individuals.

The nonnucleoside reverse transcriptase inhibitors (NNRTI) have low genetic barriers to resistance. Resistance can sometimes be overcome by increasing drug exposure. We assessed factors associated with 48-week virological response in treatment-experienced individuals receiving NNRTI therapy including resistance testing results and plasma drug exposure. Of 62 individuals assigned a new NNRTI-based regimen following resistance testing therapy consisted of efavirenz in 35 (56%) and nevirapine in 27 (44%) individuals. NNRTI fold change (FC) was determined from resistance test at baseline and plasma drug concentration at week 4. Mean time weighted change from baseline VL was -0.68 log over 48 weeks. Significant associations with change from baseline VL included baseline VL and FC whereas plasma drug concentration was not associated. In this cohort of highly treatment-experienced individuals treated with NNRTI regimens, we did not observe a significant association between NNRTI plasma concentration and virological response.

Alkynes↗

PubMed2006

Enfuvirtide in HIV-1-infected individuals changing therapy to a nucleoside reverse transcriptase inhibitor sparing regimen: the ALLIANCE Study.

The role of the fusion inhibitor enfuvirtide in nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimens was assessed in an open-label study of fifty-nine highly antiretroviral drug exposed HIV-1-infected individuals. There was a reduction in plasma HIV-1 RNA of 1.43 (95% confidence interval [Cl]: -2.06, -1.22) log10 copies/ml plasma over 96 weeks, and 44% (95% CI: 31, 58) of individuals had a viral load less than 400 copies/ml. A viral load below detection at 96 weeks was predicted by a baseline genotypic sensitivity score greater than 1. There was an average increase of 67 cells/microl (95% Cl: 15, 120) from baseline CD4+ T-cell count to week 96, and the percentage of patients with CD4+ T-cell counts above 100 and 200 cells/microl increased over the trial. Injection site reactions (ISRs) were less common in people with CD4+ T-cell counts >250 cells/microl at any time during follow-up, and were more severe in patients with lower baseline peripheral fat. Adherence over 48 weeks to enfuvirtide injections ranged from 96.3-99.5%. During the 96 week trial there were two discontinuations due to ISRs and two discontinuations following hypersensitivity reactions. Over the 96 weeks of study lean body mass increased by an average 2.7 kg (95% Cl; 1.7, 3.6 kg). Mean peripheral fat increased by 0.2 kg (95% Cl; -0.2, 0.6 kg). Baseline NRTI-associated toxicities resolved in 17% of participants during follow-up. Enfuvirtide is an important component of antiretroviral therapy in highly treatment-experienced individuals where NRTI sparing may be desirable.

Adult↗

PubMed2005

The normalized inhibitory quotient of boosted protease inhibitors is predictive of viral load response in treatment-experienced HIV-1-infected individuals.

OBJECTIVE: The normalized inhibitory quotient (NIQ) has been proposed as a measure for refining the precision of HIV resistance testing when selecting antiretroviral therapy (ART). We undertook an assessment of NIQ and 48-week virological outcome in patients commencing ritonavir-boosted protease inhibitor (PI) regimens. DESIGN: A cohort of 87 HIV-infected individuals who all had extensive prior exposure to ART were assigned a new boosted PI regimen following resistance testing. PI therapy consisted of lopinavir, indinavir, saquinavir and amprenavir at 50, 32, 11 and 6%, respectively. Fold change (FC) for each PI was determined from the resistance test at baseline. Trough drug concentration (Cmin) was determined at week 4. METHODS: NIQ was derived individually by taking the logarithm of the ratio of Cmin/FC divided by the fixed ratio of population mean trough drug concentration/clinical cut off. Associations between viral load (VL) response over 48 weeks with baseline VL, FC, Cmin, NIQ and selected PI were assessed. RESULTS: Mean change from baseline VL reduced by 0.83 log at week 48. In multivariate analyses, baseline VL and NIQ were the parameters most associated with change from baseline VL at week 48 (P = 0.012 and 0.003, respectively). FC, Cmin and selected PI were not significantly associated with VL changes. CONCLUSION: In this cohort of highly treatment-experienced individuals treated with boosted PI regimens, baseline VL and NIQ were significantly predictive of virological response over 48 weeks whereas FC and Cmin were not. These results support the use of a NIQ at week 4, as a tool for predicting response to therapy in this setting.

Antiretroviral Therapy, Highly Active↗

PubMed2005

Atazanavir trough plasma concentration monitoring in a cohort of HIV-1-positive individuals receiving highly active antiretroviral therapy.

OBJECTIVES: Atazanavir is a recently approved HIV protease inhibitor (PI). As with other PIs, careful attention to potential pharmacokinetic drug interactions in clinical practice is necessary. The aim of this study was to assess the clinical associations with plasma atazanavir concentrations in HIV-positive individuals. METHODS: Individuals established on an atazanavir-containing regimen, completed an interviewer-administered questionnaire recording atazanavir dosing characteristics, concomitant medication use and adherence. After completion, plasma atazanavir concentrations were measured. RESULTS: Of 100 individuals, mean trough plasma atazanavir concentrations (mug/L) were 282 (95% CI 95-468, n = 19) and 774 (95% CI 646-902, n = 81) in those on non- and ritonavir-boosted atazanavir regimens, respectively. Eighty-five individuals had HIV RNA <50 copies/mL. Seven individuals had atazanavir plasma concentrations below the assay limit of detection (<50 microg/L), all of whom had undetectable plasma HIV RNA. In a multivariate analysis, nevirapine use was associated with significantly lower trough atazanavir concentrations (P = 0.011) and lopinavir/ritonavir use with higher trough atazanavir concentrations (P = 0.032). Dosing characteristics (including food taken), concomitant medications (including drugs used for dyspepsia) and HIV RNA were not significantly associated with trough atazanavir concentrations. CONCLUSIONS: In this cohort, despite the wide inter-individual variability of atazanavir trough concentrations, no significant association with dosing characteristics, concomitant medication (with the exception of nevirapine and lopinavir/ritonavir) or virological response was observed. Further work is needed to assess the optimal dosing regimen when using atazanavir with nevirapine.

Anti-HIV Agents↗

PubMed2005

Sexual behaviour and human herpesvirus 8 infection in homosexual men in Australia.

BACKGROUND: Human herpesvirus 8 (HHV-8) is a common sexually transmitted agent among homosexual men, but there are few Australian data. We aimed to describe the prevalence and risk factors for seropositivity to HHV-8 in Australian homosexual men. METHODS: We conducted a prospective cohort study of 179 homosexual men in Sydney Australia in 1992-1998. Detailed data on sexual behaviour was collected annually, and HHV-8 status was determined at the end of the study by an algorithm based on results of an immunofluorescence assay and an enzyme-linked immunoassay to the K8.1 protein of HHV-8. HHV-8 DNA was detected in buffy coats using a nested qualitative PCR. RESULTS: Data on sexual behaviour in at least three interviews and HHV-8 status were available in 174 (97%) of 179 men who agreed to participate. Of these, 31 (18%) were HHV-8 seropositive, and HHV-8 DNA was detected in 5 (16%) of these. The prevalence of HHV-8 infection was much higher in HIV positive (52%) than HIV negative (11%) men (OR 8.60, 95% CI 3.55-20.86). HHV-8 infection was related to more frequent reporting of unprotected receptive anal sex (OR for most frequent versus least frequent category 3.03, 95% CI 1.01-9.03, P trend 0.02), insertive oro-anal sex (OR for most frequent v. least frequent category 3.02, 95% CI 1.15-7.93, P trend 0.02) and receptive oro-anal sex (OR for most frequent v. least frequent category 3.09, 95% CI 1.11-8.60, P trend 0.05) with casual partners. CONCLUSIONS: These data are consistent with sexual transmission of HHV-8, but the precise mode of HHV-8 transmission remains unclear. Studies to elucidate the precise mode of sexual transmission of HHV-8 need to focus on potential salivary transmission, and should collect data on the HHV-8 infection and excretion status of the sexual partner.

Adult↗

PubMed2005

Hepatitis C virus prevalence and outcomes among injecting drug users on opioid replacement therapy.

OBJECTIVES: To determine hepatitis C virus (HCV) prevalence among injecting drug users (IDUs) receiving opioid replacement therapy in a referred office setting, and assess potential needs for hepatitis C treatment and care. METHODS: Data were collected on 178 IDUs receiving opioid replacement therapy who underwent clinical assessment between January 2002 and June 2003. Standard clinic protocols included HCV and hepatitis B virus (HBV) serology, liver biochemistry and HCV RNA analysis for patients with a positive HCV antibody and normal alanine aminotransferase (ALT) levels. RESULTS: HCV prevalence was 75.3%, similar for males (75.5%) and females (74.4%), and increased with age from 60.8% for 19-30 years to 93.9% above 40 years. Among patients with HCV antibodies and no prior HCV antiviral therapy (n = 130), 53.1% had normal ALT levels and 25.4% were HCV-RNA negative. Older patients were more likely to have normal ALT levels (P = 0.02), and be HCV-RNA negative (P = 0.02). Younger patients were more likely to have been HBV vaccinated (P < 0.001), however, were less likely to have either vaccine or natural immunity (P = 0.006). Of 97 patients with probable chronic HCV infection, 58 patients met pre-liver biopsy criteria for HCV treatment, 34 had relative contraindications to treatment and 6 had been referred for treatment assessment. CONCLUSION: Clinical characterization in a setting of high HCV prevalence has enabled the differentiation of patients into groups with no evidence of HCV viraemia, with chronic HCV infection, and those most appropriate for HCV treatment referral. These clinical assessments along with appropriate referral should be instituted in drug dependency treatment settings.

Adult↗

PubMed2004

Clearance of hepatitis C virus after newly acquired infection in injection drug users.

A retrospective cohort of injection drug users with newly acquired hepatitis C virus (HCV) infection was established to examine viral clearance. Newly acquired HCV infection was defined by anti-HCV antibody seroconversion within a 2-year interval. Stored serum samples were tested for HCV RNA, with viral clearance defined as >/=2 consecutive negative HCV RNA test results after infection. Ninety-nine cases of HCV infection were identified; 57 had >/=2 HCV RNA test results after infection. Viral clearance occurred in 24 (42%) cases, with Kaplan-Meier estimated probabilities of 23%, 38%, and 40% at 6, 12, and 24 months, respectively.

Adolescent↗

PubMed2004

Reversibility of lipoatrophy in HIV-infected patients 2 years after switching from a thymidine analogue to abacavir: the MITOX Extension Study.

OBJECTIVE: To determine if long-term improvement in HIV lipoatrophy can be attained by substitution of thymidine analogues zidovudine (ZDV) or stavudine (d4T) with abacavir (ABC). DESIGN: Long-term follow-up (104 weeks) of a randomized, open-label study. SETTING: Seventeen ambulatory HIV clinics in Australia and London. SUBJECTS: Patients with HIV lipodystrophy were randomized to switch from a thymidine analogue to ABC, while continuing all other antiretroviral therapy (ABC arm) (n = 42) or continue current therapy (ZDV/d4T arm) (n = 43). INTERVENTION: At week 24, all control patients could switch to ABC. Of the original 111 patients randomized, 85 had long-term follow-up data, with 77 having imaging data available at 104 weeks. MAIN OUTCOME MEASURE: The primary endpoint was time-weighted change in limb fat mass, measured by dual-energy X-ray absorptiometry (DEXA). RESULTS: At week 104, the mean increase in limb fat for the ABC and ZDV/d4T group was 1.26 +/- 2.02 kg and 0.49 +/- 1.38 kg, respectively. The time-weighted change for limb fat was significantly different between the two arms (0.43 kg; P = 0.008). On-treatment analysis demonstrated a trend for increased limb fat in patients in the ABC arm. Visceral fat accumulation, buffalo hump, self-assessed lipodystrophy or the lipodystrophy case definition score (LCDS) did not improve. CONCLUSIONS: In patients with moderate-to-severe lipodystrophy, significant improvements in subcutaneous fat continued over 104 weeks after switching from a thymidine analogue to ABC. Nevertheless, the lipodystrophy syndrome was still evident, indicating additional strategies need evaluating.

Absorptiometry, Photon↗

PubMed2004

Changes in hematologic parameters and efficacy of thymidine analogue-based, highly active antiretroviral therapy: a meta-analysis of six prospective, randomized, comparative studies.

BACKGROUND: Hematologic changes that occur with HIV infection and antiretroviral therapy may impact the quality of life of patients and have been associated with morbidity and mortality. The management of anemia and neutropenia has improved survival in persons with HIV. OBJECTIVES: This meta-analysis was performed to assess the changes in hemoglobin (Hb) levels and neutrophil counts that occur during thymidine analogue-based triple therapy and to establish whether different regimens of triple therapy are similar in efficacy based on CD4(+) T-cell count and viral load changes. METHODS: This was a meta-analysis of the impact of zidovudine (AZT) compared with stavudine (d4T) in triple therapy regimens in HIV patients with regard to hematologic parameters and efficacy markers. The peer-reviewed literature was searched with use of MEDLINE, PubMed, EMBASE, and the Cochrane database of systematic reviews (key terms: HIV, antiretroviral therapy, CD4, viral load, three, triple, and highly active antiretroviral therapy [HAART]). Searches were initially not limited by publication type, study design, date, or language but subsequently were sorted to include only studies performed in treatment-naive adult patients; randomized; and comparative of a regimen that included d4T with a regimen that included AZT; to involve regimens that included a minimum of 3 drugs each; and to include hematologic outcomes data. Outcomes were CD4(+), viral load, and hematologic parameters. RESULTS: This meta-analysis included 6 studies. Treatment efficacy as measured by changes in CD4(+) T-cell counts and viral load did not differ significantly between regimens. Hb levels decreased with AZT treatment by a mean (SE) 0.4 (0.05) g/dL and 0.2 (0.06) g/dL at weeks 24 and 48, respectively, but increased with d4T treatment by 0.45 (0.03) g/dL and 0.58 (0.04) g/dL, respectively. All grades of anemia and neutropenia events were consistently more common with AZT-based regimens relative to d4T-based therapy. CONCLUSIONS: AZT-based HAART has a greater negative impact on hematologic parameters relative to d4T-based regimens. AZT recipients are more likely than d4T recipients to experience anemia and neutropenia events of any grade, and AZT is associated with a net decrease in Hb level relative to a net increase with d4T. These factors may influence the choice of drug used in the treatment of certain patient populations.

Anemia↗

PubMed2004

Hepatitis C virus incidence among injecting drug users on opioid replacement therapy.

OBJECTIVE: To determine hepatitis C virus (HCV) incidence among injecting drug users (IDUs) receiving opioid replacement therapy (ORT). METHODS: A retrospective cohort study was established in a primary care drug dependency treatment clinic. The cohort included all IDUs who commenced ORT after January 1996 with an initial anti-HCV antibody negative result and repeat testing prior to July 2003. HCV incidence was estimated for all subjects, with further comparison among those with continuous versus interrupted ORT. RESULTS: Fifty-four subjects were initially HCV antibody negative and had repeat testing. Five cases of HCV antibody seroconversion occurred during a total follow-up period of 131.1 person years (py), an incidence of 3.8/100 py (95% CI 1.2-8.9/ 100 py). Four seroconversions occurred in the subgroup with interrupted ORT (n=20), an incidence of 7.4/100 py (95% CI 2.0-18.9/100 py), compared with one seroconversion in the subgroup with continuous ORT (n=34), an incidence of 1.3/100 py (95% CI 0.03-7.3/100 py). CONCLUSIONS: HCV incidence among IDUs receiving ORT in our clinic was relatively low. Those IDUs without interruptions to their treatment appeared to be at particularly low risk of HCV infection. These findings support the role of ORT in HCV prevention for IDUs.

Adult↗

PubMed2002

A randomized, double-blind study of gemfibrozil for the treatment of protease inhibitor-associated hypertriglyceridaemia.

BACKGROUND: Hypertriglyceridaemia is common in patients with HIV, especially those taking protease inhibitors or with lipodystrophy, frequently observed at levels associated with accelerated cardiac disease. This study aimed to explore the efficacy and safety of gemfibrozil for hypertriglyceridemia in patients with HIV infection. METHODS: A 16-week, randomized, double-blind, comparative study of low saturated fat diet versus low saturated fat diet with gemfibrozil 600 mg twice daily in patients with triglycerides > or = 3mmol/l receiving protease inhibitor therapy. Following a 4-week period of dietary intervention alone, patients were randomized to gemfibrozil or matching placebo. The primary outcome was the difference in mean change in fasting triglycerides at week 16 between the two groups. RESULTS: 37 men were randomized (17 gemfibrozil, 20 placebo) with median fasting triglycerides 5.6 mmol/l. Mean changes in triglycerides from week 4 to week 16 were -1.22 mmol/l and +0.35 mmol/l for the gemfibrozil and placebo groups respectively (between-group mean difference of 1.57 mmol/l; 95% confidence interval, -6.7 to 3.5; = 0.08). Only one patient treated had triglycerides return to a desirable range (< or = 2.00 mmol/l). No significant changes in the other metabolic parameters were observed. Gemfibrozil was well tolerated, did not appear to induce additional protease inhibitor toxicity, and did not induce changes in CD4 lymphocyte counts or HIV RNA load. CONCLUSIONS: Gemfibrozil is safe and demonstrated at most, modest efficacy for hypertriglyceridemia in HIV-infected patients receiving protease inhibitors. Given the level of response, however, it is unclear whether these reductions will confer clinical benefit, at least in the presence of continued protease inhibitor use.

Diet↗

PubMed2002

Abacavir substitution for nucleoside analogs in patients with HIV lipoatrophy: a randomized trial.

CONTEXT: Peripheral lipoatrophy may complicate antiretroviral therapy of human immunodeficiency virus (HIV) infection, often related to duration and type of nucleoside analog therapy, and may have a mitochondrial pathogenesis. No proven therapy exists for lipoatrophy, but abacavir is a nucleoside analog that may be less toxic to mitochondria. OBJECTIVE: To determine if substitution of stavudine or zidovudine with abacavir improves HIV lipoatrophy without affecting control of HIV replication. DESIGN: Randomized, open-label 24-week study. SETTING: Seventeen hospital HIV outpatient clinics and primary care centers in Australia and England, with randomization from June 2000 through January 2001. PARTICIPANTS: A total of 111 adults (109 men) with moderate or severe lipoatrophy who were receiving stavudine (n = 85) or zidovudine (n = 26) and had stable plasma HIV RNA levels below 400 copies/mL and no prior abacavir therapy. INTERVENTION: Patients were randomly assigned to switch from stavudine or zidovudine to abacavir, 300 mg twice per day, while continuing all other antiretroviral therapy (n = 54) or to continue all antiretroviral therapy (n = 57). MAIN OUTCOME MEASURES: The primary end point was limb fat mass, measured by dual-energy x-ray absorptiometry; key secondary end points were plasma HIV RNA levels, adverse events, physician-assessed (via subjective measures) lipodystrophy severity, total and central fat mass, and fasting metabolic (lipid, glycemic, and lactate) levels. RESULTS: There was a significant increase in limb fat in the abacavir group relative to the stavudine/zidovudine group (0.39 vs 0.08 kg; mean difference, 0.31; 95% confidence interval [CI], 0.06-0.57 kg), as well as significant relative increases in subcutaneous thigh (P =.01), arm (P<.001), and abdominal (P =.001) fat areas on computed tomography. Switching had no significant effect on secondary end points, including plasma HIV RNA (for unadjusted comparison between groups at week 24, odds ratio, 1.38; 95% CI, 0.48-3.96). Change in limb fat mass at week 24 did not correlate with change in subjectively determined perceived lipoatrophy severity (r = -0.06; P =.53 by Spearman correlation). Hypersensitivity to abacavir was seen in 5 patients (10%). CONCLUSIONS: In this sample of lipoatrophic HIV-infected adults, switching from stavudine or zidovudine to abacavir for 24 weeks led to significant, albeit modest, objectively measured increases in limb fat. Clinical lipoatrophy, as assessed subjectively, did not resolve, however, and at the rate of increase observed may take years to resolve with use of this strategy. Longer-term follow-up is needed.

Absorptiometry, Photon↗

PubMedDate not supplied

Randomized, open-label, comparative trial to evaluate the efficacy and safety of three antiretroviral drug combinations including two nucleoside analogues and nevirapine for previously untreated HIV-1 Infection: the OzCombo 2 study.

PURPOSE: To assess and compare the efficacy and safety of three triple combination antiretroviral therapies in HIV-1-infected treatment-naive patients. METHOD: Seventy treatment-naive HIV-infected adults with CD4+ T-cell counts >50/microL were randomized to receive either zidovudine + lamivudine + nevirapine (AZT + 3TC + NVP), stavudine + didanosine + nevirapine (d4T+ddI+NVP), or stavudine + lamivudine + nevirapine (d4T+3TC+NVP) for 52 weeks. Patient assessments were conducted monthly and included measurement of plasma HIV RNA levels and CD4+ T-cell counts and evaluations for drug toxicity. RESULTS: The mean time-weighted reductions in plasma HIV RNA in the AZT+3TC+NVP, d4T+3TC+NVP, and d4T+ddI+NVP groups were 1.29, 2.13, and 1.78 log(10) copies/mL, respectively (p =.389). The proportions of patients with HIV RNA <50 copies/mL in the AZT+3TC+NVP, d4T+3TC+NVP, and d4T+ddI+NVP groups were 73%, 68%, and 80%, respectively (p =.71). The mean time-weighted increases in CD4+ T-cell counts in the AZT+3TC+NVP, d4T+3TC+NVP, and d4T+ddI+NVP groups were 139, 113, and 174 cells/microL, respectively (p =.30). Three patients ceased assigned treatment due to rash (one from each treatment arm), and 5 of the 45 patients on d4T (3 from the d4T+3TC+NVP arm and 2 from the d4T+ddI+NVP arm) ceased assigned treatment due to neuropathy. CONCLUSION: All three-drug combinations were equally effective at suppressing viral load and increasing CD4+ T-cell counts. No significant differences were detected between the treatment groups in virological or immunological response or cessation of study drugs due to adverse events, although it is possible that the study was underpowered to detect differences. NVP was safe and efficacious in this setting, and efficacy was not influenced by nucleoside reverse transcriptase inhibitor backbone.

Adult↗