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Biomedical subjects

Matthew Law

Publications and source records attributed to Matthew Law.

At least 37 records · Page 2Linked to original sources
PubMed2003

Cardiovascular disease risk factors in HIV patients--association with antiretroviral therapy. Results from the DAD study.

OBJECTIVE: To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-infected persons, and to investigate any association between such risk factors, stage of HIV disease, and use of antiretroviral therapies. DESIGN: Baseline data from 17,852 subjects enrolled in DAD, a prospective multinational cohort study initiated in 1999. METHODS: Cross-sectional analyses of CVD risk factors at baseline. The data collected includes data on demographic variables, cigarette smoking, diabetes mellitus, hypertension, dyslipidaemia, body mass index, stage of HIV infection, antiretroviral therapy. RESULTS: Almost 25% of the study population were at an age where there is an appreciable risk of CVD, with those receiving a protease inhibitor (PI) and/or non-nucleoside reverse transcriptase inhibitor (NNRTI) tending to be older. 1.4% had a previous history of CVD and 51.5% were cigarette smokers. Increased prevalence of elevated total cholesterol (> or = 6.2 mmol/l) was observed among subjects receiving an NNRTI but no PI [odds ratio (OR), 1.79; 95% confidence interval (CI), 1.45-2.22], PI but no NNRTI (OR, 2.35; 95% CI, 1.92-2.87), or NNRTI + PI (OR, 5.48; 95% CI, 4.34-6.91) compared to the prevalence among antiretroviral therapy (ART)-naive subjects. Subjects who have discontinued ART as well as subjects receiving nucleoside reverse transcriptase inhibitors had similar cholesterol levels to treatment-naive subjects. Higher CD4 cell count, lower plasma HIV RNA levels, clinical signs of lipodystrophy, longer exposure times to NNRTI and PI, and older age were all also associated with elevated total cholesterol level. CONCLUSION: HIV-infected persons exhibit multiple known risk factors for CVD. Of specific concern is the fact that use of the NNRTI and PI drug classes (alone and especially in combination), particularly among older subjects with normalized CD4 cell counts and suppressed HIV replication, was associated with a lipid profile known to increase the risk of coronary heart disease.

Adult↗
PubMed2003

Lactate concentrations distinguish between nucleoside neuropathy and HIV neuropathy.

We prospectively assessed serum lactate and plasma HIV viral load in 20 patients with stavudine-related nucleoside neuropathy, 10 with HIV-related distal sensory polyneuropathy (DSPN), 20 receiving stavudine but without neuropathy and 23 not receiving stavudine and without neuropathy. Raised serum lactate levels discriminated between stavudine nucleoside neuropathy and DSPN with 90% sensitivity and 90% specificity (P = 0.001). DSPN occurred despite an undetectable viral load, making it a poor discriminator.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Dendritic nanowire ultraviolet laser array.

Self-organized dendritic crystal growth is explored to assemble uniform semiconductor nanowires into highly ordered one-dimensional microscale arrays that resemble comb structures. The individual ZnO nanowires have uniform diameters ranging from 10 to 300 nm. They are evenly spaced on a stem with a regular periodicity of 0.1-2 micrometer. Under optical excitation, each individual ZnO nanowire serves as a Fabry-Perot optical cavity, and together they form a highly ordered nanowire ultraviolet laser array.

Journal Article↗
PubMed2003

Limited evolution of HIV antiretroviral drug resistance-associated mutations during the performance of drug resistance testing.

We investigated the evolution of HIV reverse transcriptase (RT)- and protease-associated antiretroviral (ARV) drug resistance mutations during the time taken to perform genotypic drug resistance testing. Thirty treatment-experienced patients who were adherent to therapy and who underwent genotypic drug resistance testing provided blood samples at randomization and when reviewing the test results (baseline). Patients remained on their existing therapy between randomization and baseline. The predominant HIV strains in 10 patients (33%) either lost and/or gained primary RT inhibitor (RTI)- or protease inhibitor (PI)-associated resistance mutations during the testing period. Of the 9 patients with RT mutations, 2 lost, 5 gained, and 2 both lost and gained RTI resistance mutations. One patient gained a significant PI-associated resistance mutation on an existing PI-resistant background. The evolution that occurred in the RT may have altered the effectiveness of subsequent ARV therapy in some patients. Neither viral load at randomization, ARV drug class used at randomization, time between collection of blood samples, duration of current therapy, nor number of ARV drugs used influenced gain or loss of resistance mutations. There was a significant association between duration of previous ARV therapy and gain of RTI-associated resistance mutations ( p =.02), however. In general, our results suggest that patients should continue current therapy until test results are available. A few patients would be expected to gain ARV drug-associated resistance mutations during this time, however.

Adult↗
PubMed2003

Epidemiology of hepatitis C virus infection in Australia.

BACKGROUND: Since the discovery in 1989 of hepatitis C virus (HCV) as the infectious agent responsible for the vast majority of post-transfusion non-A non-B hepatitis the patterns of transmission and clinical consequences of this highly prevalent flavivirus have been widely studied. OBJECTIVE: This paper reviews available evidence on the epidemiology of HCV infection in Australia, including HCV notification data obtained through public health surveillance systems, HCV seroprevalence surveys among high risk populations, and models for estimating and projecting HCV transmission and long-term consequences of chronic HCV infection. RESULTS: Over the period 1990-2000 approximately 160,000 notifications of HCV infection were received by State and Territory health jurisdictions making it the most commonly notified communicable disease in Australia. Approximately 210,000 people are estimated to be living with HCV infection in Australia, with an estimated 80% having acquired their infection through injecting drug use. Less than 500 cases of newly acquired HCV infection are notified each year, however, an estimated 16,000 new infections occur annually. Despite the widespread introduction of needle and syringe programmes in the late 1980s, HCV transmission continues at high levels among current injecting drug users (IDUs) with incidence and prevalence estimates of 10-20/100 person years and 50-55%, respectively. Levels of HCV transmission are particularly high in both younger and incarcerated IDUs. In contrast to HCV infection, prevalence of HIV among current IDUs has remained below 2% since 1995. Although a small minority of people with chronic HCV infection will develop liver failure or hepatocellular carcinoma, the incidence of these advanced disease complications is estimated to double over the next decade. CONCLUSION: The epidemic of HCV infection continues to escalate in Australia, predominantly through transmission related to injecting drug use. As the population of people with chronic HCV infection and progressive liver disease expands the public health burden of advanced disease complications will be considerable.

Adolescent↗
PubMed2003

Estimating the effect of antiretroviral treatment during HIV seroconversion: impact of confounding in observational data.

OBJECTIVE: To assess whether treatment with antiretroviral drugs within the first 3 months of infection with HIV affects medium-term health outcomes. DESIGN AND METHODS: Data from 20 cohorts in Europe and Australia were used Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE). Analysis was restricted to persons seroconverting in 1988-1998 who started antiretroviral treatment in the first 3 months or 1-2 years from seroconversion. The relationship between times to low CD4 count, AIDS and death and time of initiation of treatment was estimated using proportional hazards models. RESULTS: Seroconversion illness was more common in those who began antiretroviral treatment in the first 3 months (73%) than in those who started treatment within 1-2 years post-seroconversion (33%). Subjects receiving early antiretroviral treatment had times to AIDS and to CD4 counts <200 cells/microL that were intermediate between those of subjects starting treatment within 1-2 years and those of the subset of these subjects starting treatment within 1-2 years who also had a prior CD4 count of >350 cells/microL and no prior AIDS diagnosis. CONCLUSIONS: On the basis of these analyses, the effect of antiretroviral treatment initiation during HIV seroconversion is uncertain. It may result in lower rates of progression compared with starting antiretroviral treatment at 1-2 years, but the early antiretroviral treatment group had a similar or even higher incidence of low CD4 counts and AIDS events than the group who started antiretroviral treatment within 1-2 years with CD4 counts over 350 cells/microL and no prior AIDS diagnosis. Estimates of the effect of early treatment are probably confounded with a number of factors, including, in particular, reasons for treatment initiation.

Adult↗
PubMed2003

Natural history models for hepatitis C-related liver disease: different disease progression parameters for different settings.

An understanding of the natural history of hepatitis C virus (HCV) infection has improved in recent years. Estimates of liver disease progression among people with chronic hepatitis C have been developed from various study populations, including liver clinics, post-transfusion hepatitis C cohorts and community-based cohorts. These estimates can be used in hepatitis C natural history models; however, they need to be matched to differing requirements. Estimation and projection of liver disease burden at the population level requires estimates of HCV prevalence and incidence, and disease progression among all people with chronic hepatitis C. Liver disease progression based on community cohorts would appear the most appropriate for a population level model. In contrast, models that examine the cost-effectiveness of antiviral therapy for people with chronic hepatitis C require disease progression estimates from the treatment setting. Further models are required to determine individual prognosis and should be based on an assessment of cofactors for liver disease progression.

Antiviral Agents↗
PubMed2003

HIV lipodystrophy case definition using artificial neural network modelling.

OBJECTIVE: A case definition of HIV lipodystrophy has recently been developed from a combination of clinical, metabolic and imaging/body composition variables using logistic regression methods. We aimed to evaluate whether artificial neural networks could improve the diagnostic accuracy. METHODS: The database of the case-control Lipodystrophy Case Definition Study was split into 504 subjects (265 with and 239 without lipodystrophy) used for training and 284 independent subjects (152 with and 132 without lipodystrophy) used for validation. Back-propagation neural networks with one or two middle layers were trained and validated. Results were compared against logistic regression models using the same information. RESULTS: Neural networks using clinical variables only (41 items) achieved consistently superior performance than logistic regression in terms of specificity, overall accuracy and area under the ROC curve. Their average sensitivity and specificity were 72.4 and 71.2%, as compared with 73.0 and 62.9% for logistic regression, respectively (area under the ROC curve, 0.784 vs 0.748). The discriminating performance of the neural networks was largely unaffected when built excluding 13 parameters that patients may not have readily available. The average sensitivity and specificity of the neural networks remained the same when metabolic variables were also considered (total 60 items) without a clear advantage against logistic regression (overall accuracy 71.8%). The performance of networks considering also body composition variables was similar to that of logistic regression (overall accuracy 78.5% for both). CONCLUSIONS: Neural networks may offer a means to improve the discriminating performance for HIV lipodystrophy, when only clinical data are available and a rapid approximate diagnostic decision is needed. In this context, information on metabolic parameters is apparently not helpful in improving the diagnosis of HIV lipodystrophy, unless imaging and body composition studies are also obtained.

Absorptiometry, Photon↗
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

Dynamics of T cells and TCR excision circles differ after treatment of acute and chronic HIV infection.

We quantified T cell proliferation and thymic function in primary HIV infection (PHI; n = 19) and chronic HIV infection (CHI; n = 14) by measuring Ki67 staining and TCR excision circle (TREC) number. After antiretroviral therapy of PHI there is a profound decrease in the number and percentage of Ki67(+) T cells (<6% Ki67(+)) with no significant increase in TREC per million cells and a transient increase in TREC per milliliter. In contrast, after antiretroviral therapy of CHI there is a reduction in the percentage but little change in the total number of Ki67(+)CD4(+) T cells associated with increases in both TREC per million cells and TREC per milliliter. Using a mathematical model that accounts for proliferation, death, and redistribution of T cells, we find that redistribution is consistent with the TREC changes observed during treatment of PHI and that an increase in thymic output is needed to explain the increase in TREC during treatment of CHI. Consideration of TREC per milliliter shows that changes in proliferation alone cannot explain the changes in TREC. In addition, although increased proliferation of memory cells in HIV infection has been established, we find no difference in TREC per million CD45RA(-) "memory" T cells between healthy and infected individuals (p = 0.154 for CD4(+); p = 0.383 for CD8(+)). Finally, although the number of TREC per million cells is always much lower in memory T cells than in naive T cells, in the setting of HIV infection, given that memory cells make up a larger proportion of total T cells, we find that 50% of TREC per milliliter in CD4(+) T cells is harbored in the CD45RA(-) "memory" subset of our infected subjects.

Acute Disease↗
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↗
PubMed2002

Estimation of risk of cancers before occurrence of acquired immunodeficiency syndrome in persons infected with human immunodeficiency virus.

There is methodological debate as to whether cohorts defined by acquired immunodeficiency syndrome (AIDS) diagnosis can be used to estimate risks of cancer in persons with human immunodeficiency virus (HIV) before AIDS. The authors compared risks of non-AIDS-defining cancers before AIDS in persons with HIV using a cohort based on AIDS diagnosis and a second cohort based on HIV diagnosis. National population-based registries of AIDS and HIV diagnoses to August 1999 were matched separately with the National Cancer Registry in Australia. Four analyses were performed. In analysis 1, follow-up was from 5 years before AIDS registration in 8,118 persons with AIDS. Analysis 2 was similar but adjusted expected numbers of cancers for decreased survival. Analysis 3 was based on 7,061 persons registered with HIV, with follow-up from the reported date of diagnosis. Analysis 4 was based on 2,112 AIDS cases previously reported with HIV, with follow-up from 5 years before AIDS diagnosis. In all analyses, follow-up ended at cancer diagnosis, death, 6 months before AIDS, or the end of available cancer data, whichever occurred first. For 10 types of cancer there were at least three cases in any one of the analyses. For these cancers there was no systematic pattern such that one analysis produced consistently higher or lower estimates than the others. These analyses suggest that cancer risk in persons with HIV before AIDS diagnosis may be estimated reliably based on cancer experience 5 years before AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Is severe liver disease a common outcome for people with chronic hepatitis C?

For people with chronic hepatitis C, an assessment of their risk of progression to advanced liver disease is a major priority. Early studies of the natural history of chronic hepatitis C suggested that development of cirrhosis was a relatively common outcome, even in the first 20 years of infection. These studies were either cross-sectional liver clinic series of people referred for assessment to specialist clinics, or longitudinal cohorts of people with post-transfusion hepatitis. More recent studies (particularly longitudinal community-based cohorts) indicate that liver disease progression is generally slow, and that a minority of people with chronic hepatitis C will develop advanced liver disease. Based on an extensive review of studies reporting on chronic hepatitis C natural history, we have developed a Markov model of liver disease progression. This model estimates that the risk of progression to cirrhosis is 7% and 20% after 20 and 40 years of infection, respectively. Corresponding estimates for hepatitis C-related mortality are 1% and 4%. However, liver disease progression is highly variable, and certain subgroups of people with chronic hepatitis C are at increased risk of advanced liver disease. Those groups include people with a heavy alcohol intake, those who have coinfection with HIV or HBV, and those who have already progressed to moderate to severe hepatic fibrosis.

Disease Progression↗
PubMed2002

Analysis of virological efficacy in trials of antiretroviral regimens: drawbacks of not including viral load measurements after premature discontinuation of therapy.

OBJECTIVES: To compare two analytic approaches to assess the virological effect of HAART according to the intention-to-treat (ITT) principle. MATERIAL: Data from 2318 patients enrolled in 10 randomised clinical trials (RCTs) and from 3091 patients followed in an observation cohort (EuroSIDA) starting their first HAART regimen. METHODS: Two classifications of defining virological response 48 weeks after starting the therapy to be evaluated were compared: 1) only patients remaining on the therapy and having a plasma viral load (pVL) below a given cut-off level at week 48 were classified as responders (ITT/s=f); and 2) patients with a pVL below a given cut-off at week 48 whether they remained on initial assigned therapy or switched therapy were responders (ITT/s incl). In both analyses, patients with missing data at week 48 were classified as failures (i.e., non-responders). RESULTS: According to ITT/s=f, 22-70% of the patients starting a HAART regimen in a RCT experienced a virological response at week 48. Only two RCTs had complete follow-up data (n=424): between 29 and 62% achieved a virological response at week 48 in the six treatment arms evaluated in the studies according to ITT/s=f, and 41-72% according to ITT/s incl. Among those who discontinued the therapy to be evaluated in these two trials, 13-45% (cohort: 39-74%) subsequently experienced a virological response at week 48. The subsequent response rates were associated with the reason for discontinuation (toxicity versus confirmed virological failure: 63 vs 33%), varied largely across regimens and were not associated with the discontinuation rate. CONCLUSIONS: Discontinuation of follow-up at switch from the therapy to be evaluated remains common in antiretroviral treatment trials, but leads to an imprecise and incomplete assessment of the intrinsic effect of a given regimen. Complete follow-up of all patients should be encouraged strongly as this will allow for several complementary analytic approaches and a focus on optimal treatment strategies rather than specific regimens.

Antiretroviral Therapy, Highly Active↗
PubMedDate not supplied

Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes.

BACKGROUND: Treatment strategies for patients in whom HIV replication is not suppressed after exposure to several drug classes remain unclear. We aimed to assess the inter-relations between viral load, CD4-cell count, and clinical outcome in patients who had experienced three-class virological failure. METHODS: We undertook collaborative joint analysis of 13 HIV cohorts from Europe, North America, and Australia, involving patients who had had three-class virological failure (viral load >1000 copies per mL for >4 months). Regression analyses were used to quantify the associations between CD4-cell-count slope, HIV-1 RNA concentration, treatment information, and demographic characteristics. Predictors of death were analysed by Cox's proportional-hazards models. FINDINGS: 2488 patients were included. 2118 (85%) had started antiretroviral therapy with single or dual therapy. During 5015 person-years of follow-up, 276 patients died (mortality rate 5.5 per 100 person-years; 3-year mortality risk 15.3% (95% CI 13.5-17.3). Risk of death was strongly influenced by the latest CD4-cell count with a relative hazard of 15.8 (95% CI 9.28-27.0) for counts below 50 cells per microL versus above 200 cells per microL. The latest viral load did not independently predict death. For any given viral load, patients on treatment had more favourable CD4-cell-count slopes than those off treatment. For patients on treatment and with stable viral load, CD4-cell counts tended to be increasing at times when the current viral load was below 10000 copies per mL or 1.5 log10 copies per mL below off-treatment values. INTERPRETATION: In patients for whom viral-load suppression to below the level of detection is not possible, achievement and maintenance of a CD4-cell count above 200 per microL becomes the primary aim. Treatment regimens that maintain the viral load below 10000 copies per mL or at least provide 1.5 log10 copies per mL suppression below the off-treatment value do not seem to be associated with appreciable CD4-cell-count decline.

Adult↗
PubMedDate not supplied

Progression of lipodystrophy (LD) with continued thymidine analogue usage: long-term follow-up from a randomized clinical trial (the PIILR study).

PURPOSE: During the 24-week PIILR study of protease inhibitor (PI) withdrawal, improved lipids and reduction in intraabdominal visceral fat was seen, however, there was also a loss of subcutaneous limb fat in patients with HIV-lipodystrophy (LD). It was hypothesized that overall improvement in LD may require a longer period of time off PIs. METHOD: Follow-up of patients randomized to stop or continue PI-based therapy for 24 weeks, in a multicenter study, was continued for up to 120 weeks. Biochemistry and lipid parameters were assessed every 3 months. DEXA and CT scans were performed annually. Limb fat, visceral adipose tissue, and the lipodystrophy case definition score (LCDS) were used as indicators of LD severity. RESULTS: Forty-five male patients with baseline and week 120 body composition data were assessed. There were no significant changes in the limb fat or visceral adipose tissue (VAT) components of LD, with the exception of the LCDS (change from baseline +5.79, p < .001). Control of viral replication was maintained and lipid and glycemic parameters were unchanged over the 120-week follow-up. Linear regression analysis showed on-study usage of stavudine was independently and significantly correlated with both decreased limb fat mass and a higher LCDS. CONCLUSION: Body composition or metabolic features of LD did not improve over 2 years of observation in patients remaining on predominantly PI-sparing therapy. LD was adversely influenced by continued stavudine use.

Abdomen↗
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↗