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Biomedical subjects

David A Cooper

Publications and source records attributed to David A Cooper.

At least 55 records · Page 3Linked to original sources
PubMed2005

Buffalo hump seen in HIV-associated lipodystrophy is associated with hyperinsulinemia but not dyslipidemia.

Accumulation of dorsocervical fat, or a "buffalo hump" (BH), is commonly reported in adults with HIV-associated lipodystrophy (HIVLD). The pathogenesis underlying this aspect of a syndrome characterized by loss of subcutaneous fat from other body sites is poorly understood. We aimed to identify risk factors for a BH in HIV-infected adults in cross-sectional analyses of 2 HIV-infected ambulatory populations. The first group (Australian Lipodystrophy Prevalence Survey [APS]) consisted of 1348 Australian HIV-infected adults (95% male) irrespective of changes in body composition. The second group (Lipodystrophy Case Definition [LDCD] study) comprised 417 subjects (83% male) with at least 1 reported moderate or severe feature of HIVLD. A BH was reported in 24 (2%) APS subjects and 79 (19%) LDCD study subjects. A BH was not an isolated finding. Patients with a BH had a high prevalence of other features of HIVLD, similar to lipodystrophic patients without a BH, such as facial lipoatrophy reported in 100% and 61% BH-positive subjects from the APS and LDCD study, respectively. In both groups, those with a BH had higher fasting insulin (P<or=0.007), a higher body mass index (P<or=0.003), a higher waist/hip ratio (P<or=0.001), higher limb fat (P<or=0.003), and higher systolic blood pressure (P<0.05). On multivariate analysis, higher serum insulin, systolic blood pressure, age, and duration of exposure to ritonavir were independently associated with a BH in the APS group. In the LDCD group, higher insulin, diastolic blood pressure, and duration of exposure to zidovudine were independently associated with a BH. There was no association between a BH and hyperlipidemia. These data show that a BH is associated with other physical features of the lipodystrophy phenotype and suggest that hyperinsulinemia, a feature common to HIVLD, obesity, and hypercortisolism, is an important component of this phenotype, thus warranting closer monitoring of BH-positive patients for glucose intolerance and diabetes.

Adult↗
PubMed2005

HIV disease progression in a patient cohort treated via a clinical research network in a resource limited setting.

OBJECTIVE: To examine HIV disease progression in a cohort of adult patients treated with antiretroviral therapy (ART) via a clinical research network in Thailand. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: A cohort of 417 patients enrolled in a series of randomized ART trials, between 1996 and December 2002. MAIN OUTCOME MEASURES: Progression to combined endpoint of AIDS defining illness or death according to baseline characteristics, ART used, immunological and virological responses to initial 6 months of ART. RESULTS: During 1677 person years of follow-up, 29 of 417 patients progressed; tuberculosis was the most common event defining progression (14 of 29 events). The rates of progression to combined endpoint or death alone were 1.7 [95% confidence interval (CI), 1.1-2.4] and 0.7 (95% CI, 0.3-1.3) per 10 person years respectively. Compared to patients with baseline CD4 cell counts > or =350 x 10/l, the adjusted hazard ratio (HR) for progression was 3.67 (95% CI, 1.31-10.27) for patients with <200 x 10 cells/l. Responses to 6 months of therapy were the strongest predictors of disease progression; compared to patients with undetectable viral load at 6 months, HR for progression was 4.95 (95% CI, 2.14-11.46) for viral load >4 log10. Compared to patients with a 6-month CD4 cell count > or =350 x 10/l, HR for progression was 5.22 (95% CI, 1.90-14.37) for patients with <200 x 10 cells/l. CONCLUSIONS: HIV-infected patients in Thailand who had access to ART, appropriate care, CD4 cell and viral load monitoring facilities via a clinical research network had progression rates comparable to those in developed countries. In this setting, ART initiation could generally be delayed until the CD4 cell count approaches 200 x 10/l.

AIDS-Related Opportunistic Infections↗
PubMed2005

Incidence and risk factors for rash in Thai patients randomized to regimens with nevirapine, efavirenz or both drugs.

OBJECTIVE: To determine the incidence and risk factors for rash in Thai patients taking four different non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. METHODS: HIV-positive, antiretroviral-naive patients enrolled in the 2NN study in Thailand and followed for at least 1 week were included. Patients were randomized to efavirenz (EFV) 600 mg once daily (OD) versus nevirapine (NVP) 200 mg twice daily (BD) versus NVP 400 mg OD versus NVP 400 mg OD + EFV 800 mg OD with stavudine/lamivudine. RESULTS: Of 202 patients, 95 (47%) and 69 (34.2%) developed a rash from all reasons and from NNRTI, respectively. For NNRTI-related rash the incidences were EFV (20%), NVP BD (21%), NVP OD (38%) and NVP + EFV (67%). The proportions of patients with grade I, II and III within the four treatment arms are as follows: EFV, 4.3, 13 and 2.9%; NVP BD, 2.3, 15.9 and 2.3%; NVP OD, 12.8, 19.1 and 6.4%; and NVP + EFV, 11.9, 47.6 and 7.1%. Multivariate analyses showed females with CD4 cell count > or =250 x 10 cells/l, high body mass index (>21.3 kg/m), and a rise in CD4 (> or =53 x 10 cells/l) and alanine aminotransferase (ALT) (> or =34 U/l) at week 4 to be risk factors for rash. CONCLUSIONS: Thai patients had a high incidence of NNRTI-related rash when treated with NVP + EFV or NVP OD. NVP if used BD had the same rash incidence as EFV for rash of all grades. Females, and persons with earlier HIV disease or with a large rise in CD4+ cell count after starting therapy are at greater risk for NNRTI-related rash.

Adult↗
PubMed2005

A prospective, randomized trial of structured treatment interruption for patients with chronic HIV type 1 infection.

BACKGROUND: Structured treatment interruption was evaluated in 74 patients who had been pretreated with antiretrovirals, consisting of 2 nucleoside reverse-transcriptase inhibitors (NRTIs) for 1 year followed by 3 years of highly active antiretroviral therapy containing a protease inhibitor. METHODS: Patients with a CD4 cell count of > or =350 cells/microL and a plasma viral load of <50 copies/mL were randomized to 3 therapy arms: (1) continuous therapy, (2) CD4 cell count-guided theory, and (3) week-on/week-off (WOWO) therapy. The efficacy and safety of structured treatment interruption and antiretroviral use were evaluated in human immunodeficiency type 1 (HIV-1)-infected patients. The study end points were percentage of patients who developed AIDS or who died and a CD4 cell count of > or =350 cells/microL. Intergroup differences were analyzed using analysis of variance and Kruskal-Wallis tests. RESULTS: Baseline characteristics at the start of the structured treatment interruption were similar. At week 48, no patient had died, and 1 patient in the WOWO group had an AIDS-defining condition. The proportions of patients with a CD4 cell count of > or =350 cells/microL were 100%, 87%, and 96% in treatment arms 1, 2, and 3, respectively. The percentages of weeks of antiretroviral use were 100%, 41.1%, and 69.8% in arms 1, 2, and 3, respectively. The adverse events were not significantly different among arms (P=.27). Thirty-one percent of patients in the WOWO group experienced virological failure. CONCLUSION: WOWO therapy maintained a CD4 cell count of > or =350 cells/microL in almost all patients but was associated with high virological failures rates (possibly resulting from previous dual-NRTI therapy), indicating that this strategy is less useful. Receipt of CD4 cell count-guided therapy resulted in comparable clinical outcomes to continuous therapy and may save antiretroviral-associated costs, but this needs to be confirmed by a larger trial.

Adult↗
PubMed2005

Long-term survival and concomitant gene expression of ribozyme-transduced CD4+ T-lymphocytes in HIV-infected patients.

BACKGROUND: An anti-HIV-1 tat ribozyme, termed Rz2, has been shown to inhibit HIV-1 infection/replication and to decrease HIV-1-induced pathogenicity in T-lymphocyte cell lines and normal peripheral blood T-lymphocytes. We report here the results of a phase I gene transfer clinical trial using Rz2. METHODS: Apheresis was used to obtain a peripheral blood cell population from each of four HIV-negative donors. After enrichment for CD4+ T-lymphocytes, ex vivo expansion and genetic manipulation (approximately equal aliquots of the cells were transduced with the ribozyme-containing (RRz2) and the control (LNL6) retroviral vector), these cells were infused into the corresponding HIV-1-positive twin recipient. Marking was assessed over an initial 24-week period and in total over an approximate 4-year period. RESULTS: The gene transfer procedure was shown to be safe, and technically feasible. Both RRz2- and LNL6-gene-containing peripheral blood mononuclear cells (PBMC) were detected at all time points examined to 4 years. There was concomitant gene construct expression in the absence of the need for ex vivo peripheral blood cell stimulation and there was no evidence of immune elimination of the neoR T-lymphocytes nor of silencing of the Moloney murine leukemia virus long terminal repeat. CONCLUSIONS: The proof of principle results reported here demonstrate safety and feasibility of this type of gene transfer approach. While not specifically tested, T-lymphocytes containing an anti-HIV gene construct may impact on HIV-1 viral load and CD4+ T-lymphocyte count, potentially representing a new therapeutic modality for HIV-1 infection.

Adult↗
PubMed2005

A new variant cytotoxic T lymphocyte escape mutation in HLA-B27-positive individuals infected with HIV type 1.

The immune response in HIV-infected individuals who carry HLA-B27 is characterized by an immunodominant cytotoxic T lymphocyte (CTL) response to a conserved epitope corresponding to amino acids 263-272 of HIV-1 p24 gag. The arginine at position 264 is a crucial anchor residue. Amino acid substitution at 264 from arginine (R) to glycine (G), lysine (K), or threonine (T) results in a low affinity peptide that binds to HLA-B27 inefficiently and is poorly recognized by T cells that respond to the wild-type peptide. These mutants have been characterized as CTL escape mutations. We studied the plasma virus of 20 HLA-B27 longterm nonprogressors: 14 were wild type and 6 were found to be mutant. Five of these carried known escape mutations coding for K or G at position 264. One patient demonstrated a previously undescribed R264Q mutation in 30/31 clones. This altered epitope failed to elicit an IFN-gamma response from PBMC isolated from any of four HLA-B27-positive individuals with strong responses to wild-type peptide. A peptide binding assay confirmed that the R264Q mutant peptide had 30-fold lower binding affinity to HLA-B27 compared to wild type. Therefore, the R264Q variant is a likely novel escape mutation in HLA-B27-positive individuals.

Amino Acid Sequence↗
PubMed2005

Influence of rosiglitazone on flow-mediated dilation and other markers of cardiovascular risk in HIV-infected patients with lipoatrophy.

BACKGROUND: Antiretroviral therapy for HIV infection is commonly complicated by lipoatrophy, insulin resistance and dyslipidaemia. In HIV-uninfected adults with insulin resistance or type 2 diabetes, thiazolidinediones can lower blood pressure and improve both insulin sensitivity and endothelial function. This study sought to investigate the effects of rosiglitazone on endothelial function and other markers of cardiovascular risk in patients with HIV-related lipoatrophy. METHODS: HIV-infected, lipoatrophic adults receiving antiretroviral therapy were randomized to receive either rosiglitazone 4 mg or matched placebo, twice daily. Percentage flow-mediated forearm arterial dilation (FMD%) was measured at weeks 0, 12, 24 and 48, together with other markers of vascular risk (blood pressure, lipids, glycaemic parameters, adiponectin and leptin). RESULTS: Out of 64 enrolled adults, 44 (69%) attended all visits (23 rosiglitazone, 21 placebo). Relative to placebo, at week 48, rosiglitazone decreased systolic blood pressure (8 mmHg, P=0.03), insulin (3 microIU/ml, P=0.02), insulin resistance (P=0.03) and leptin (0.6 ng/ml, P=0.02), whilst adiponectin was increased (3.3 microg/lml, P<0.0001). However, rosiglitazone increased total cholesterol (49.1 mg/dl, P=0.001), low-density lipoprotein cholesterol (23.5 mg/dl, P=0.01) and triglycerides (146 mg/dl, P=0.06). Mean baseline FMD% for the entire cohort was moderately impaired (4.5%). Compared with baseline, mean on-treatment FMD% increased by 0.8% with rosiglitazone and decreased by 0.3% with placebo, (mean difference 1.1%, 95% CI -0.2 to 2.5, P=0.09). CONCLUSIONS: Rosiglitazone has minimal effect on flow-mediated dilation in HIV-infected lipoatrophic adults. However, despite worsening of the lipid profile, the overall effect of rosiglitazone on the cardiovascular risk profile in these subjects was positive.

Adult↗
PubMed2005

Methodological considerations in human studies of gene expression in HIV-associated lipodystrophy.

In the majority of cases, HIV-associated lipodystrophy, lipoatrophy in particular, becomes clinically apparent only after months or years of continuous exposure to antiretroviral medications and, once developed, is difficult to reverse. Many lipid-related side effects of antiretroviral medications result from drug-induced changes in gene expression. As our understanding of the pathogenic mechanisms underlying HIV-associated lipodystrophy improves, it is important to be able to explore changes at a molecular level in order to fully elucidate the mechanisms whereby antiretroviral drugs exert their toxicities. Monitoring changes in gene expression in vivo may enable physicians to identify, predict or prevent drug toxicities early, before irreversible changes in body composition occur. However, monitoring changes in gene expression at a population level presents many methodological challenges that need to be addressed, over and above the considerable intra- and inter-individual variability inherent in the cellular expression of any gene. Careful collection and processing of adequate biological samples, robust laboratory processes and assays, and appropriate study design can help overcome many of these difficulties.

CCAAT-Enhancer-Binding Proteins↗
PubMed2005

A prospective study of efficacy and safety of once-daily saquinavir/ritonavir plus two nucleoside reverse transcriptase inhibitors in treatment-naive Thai patients.

OBJECTIVE: To assess the efficacy and safety of first-line treatment with once-daily saquinavir/ritonavir with two nucleoside reverse transcriptase inhibitors (NRTIs), as induction therapy before enrollment in a randomized trial of structured treatment interruption strategies. DESIGN: Two-hundred antiretroviral-naive patients with CD4+ cell counts between 200-350 at screening were enrolled in this open-label 24week study. METHODS: Patients were followed up every 8 weeks for CD4+ cells, HIV RNA, and clinical and laboratory toxicities. RESULTS: Two-hundred patients were enrolled with median baseline CD4+ cell count of 267 cells/microl and HIV RNA 50 118 (4.7 log10) copies/mi. After 24 weeks of treatment, 191 of 200 (96%) patients had below 400 copies/ml HIV RNA, with 177/200 (89%) below 50 copies/ml (intent to treat, missing equals failure method), with a median rise in CD4+ cell count of 122 cells/microl. There was no significant correlation between the minimum concentration of saquinavir and HIV RNA reductions at week 8 (P = 0.957) or absolute HIV RNA at week 24 (P = 0.77). CONCLUSION: First-line highly active antiretroviral therapy (HAART) with once-daily saquinavir/ritonavir plus two NRTIs showed strong antiviral efficacy over 24 weeks, and should be evaluated in larger prospective randomized clinical trials.

Adult↗
PubMed2005

Nevirapine plasma concentrations and concomitant use of rifampin in patients coinfected with HIV-1 and tuberculosis.

OBJECTIVES: In countries with high numbers of HIV/tuberculosis coinfection nevirapine and rifampin are used extensively. However, limited data are available about whether or not nevirapine and rifampin can be safely coadministered without the plasma concentration of nevirapine falling below therapeutic levels. METHODS: Blood samples for determination of nevirapine plasma concentrations were collected from patients using nevirapine 200 mg twice daily with or without concomitant rifampin. Bivariate and multivariate linear regression models were used to investigate factors possibly related to nevirapine concentrations. RESULTS: We received 74 blood samples from patients using nevirapine plus rifampin, and collected blood samples from an equal number of controls using nevirapine only. Groups were similar for age, gender, weight, height and body mass index (BMI). In the rifampin group the mean nevirapine concentration was 5.47 +/- 2.66 mg/l, whereas in the control group the mean nevirapine concentration was 8.72 +/- 3.98 mg/l. In the rifampin group seven nevirapine trough concentrations were low (< 3.1 mg/l), while in the control group two patients had low nevirapine trough concentrations (P = 0.164). In the multivariate linear regression analysis, corrected for time after drug intake, the use of rifampin was significantly (P < 0.001) associated with lower nevirapine plasma concentrations, whereas higher BMI reached borderline significance (P = 0.065). CONCLUSION: Although nevirapine plasma concentrations were 3.3 mg/l lower when co-administered with rifampin, still more than 86% of these patients had nevirapine plasma concentrations > 3.1 mg/l. Our results suggest that from a pharmacological point of view the majority of Thai coinfected patients, who have low BMIs, reach nevirapine plasma concentrations that are adequate for treatment of HIV. However this can only be undertaken if nevirapine plasma concentration monitoring is available and can be closely followed.

Anti-Infective Agents↗
PubMed2004

The incubation period of acute retroviral syndrome as a multistep process: a parametric survival analysis.

A long duration of acute retroviral syndrome (ARS) and a short incubation of ARS (IncARS) are independent predictors of a fast progression to AIDS. The first objective of this study was to validate previous estimates of IncARS by comparing durations between health care workers (HCWs) accidentally infected by HIV and individuals infected by other routes (non-health care workers [N-HCWs]). The second objective was to use parametric survival models to generate hypotheses on various steps occurring during the IncARS. Data from a prospective cohort of patients with documented ARS and from individuals with ARS as the result of accidental exposure to HIV were analyzed. Nonparametric and parametric survival models were used to describe the incubation of ARS. No differences were found for the median IncARS between 34 HCWs (21.5 days) and 70 N-HCWs (21.5 days) (log-rank test, P = 0.72). According to survival models, IncARS can be modeled with a gamma and/or lognormal model with means of 26.4 days and 26.7 days, respectively. The gamma model suggests that 3 sequential stages are present during the IncARS, which is compatible with basic science investigations identifying crossing of the epithelial barrier by the virus, the virus-host cell interactions, and the viral systemic dissemination.

Cohort Studies↗
PubMed2004

Evaluation in macaques of HIV-1 DNA vaccines containing primate CpG motifs and fowlpoxvirus vaccines co-expressing IFNgamma or IL-12.

Induction of HIV-specific T-cell responses by vaccines may facilitate efficient control of HIV. Plasmid DNA vaccines and recombinant fowlpoxvirus (rFPV) vaccines are promising HIV-1 vaccine candidates, although either vaccine alone may be insufficient to protect against HIV-1. A consecutive immunisation strategy involving priming with DNA and boosting with rFPV vaccines encoding multiple common HIV-1 antigens was further evaluated in 30 macaques. The DNA vaccine vector included CpG immunostimulatory molecules, and rFPV vaccines were compared with rFPV vaccines co-expressing the pro-T cell cytokines IFNgamma or IL-12. Vaccines expressed multiple HIV-1 genes, mutated to remove active sites of the HIV proteins. The vaccines were well tolerated, and a significant enhancement of DNA-vaccine primed HIV-1 specific T lymphocyte responses was observed following rFPV boosting. Co-expression of IFNgamma or IL-12 by the rFPV vaccines did not further enhance immune responses. Non-sterilising protection from a non-pathogenic HIV-1 challenge was observed. This study provides evidence of a safe, optimised, strategy for the generation of T-cell mediated immunity to HIV-1.

AIDS Vaccines↗
PubMed2004

Bosentan for the treatment of human immunodeficiency virus-associated pulmonary arterial hypertension.

Clinical studies have shown the importance of endothelin as a pathogenic mediator in pulmonary arterial hypertension (PAH). We describe the effects of bosentan, an oral dual endothelin receptor antagonist, in patients with PAH associated with human immunodeficiency virus (HIV) infection. In this prospective study, 16 patients with PAH associated with HIV infection in stable condition received bosentan for 16 weeks. Efficacy endpoints included exercise capacity, cardiopulmonary hemodynamics, Doppler echocardiography, New York Heart Association functional class, and quality of life (SF-36 and EQ-5D). Safety was assessed by laboratory tests, vital signs, and adverse events. Improvements were observed from baseline to Week 16 in all efficacy parameters: 6-minute walk distance (+91 +/- 60 m, p < 0.001), New York Heart Association class (14 patients improved), hemodynamics (cardiac index: +0.9 +/- 0.7 L/minute/m(2), p < 0.001), Doppler echocardiographic variables, and quality of life. During the study, no patient died and none required epoprostenol treatment. Hepatic tolerability was similar to that reported in patients with PAH. Bosentan had no negative impact on control of HIV infection. Although limited by uncontrolled design, small sample size and short duration, this study suggests that bosentan may benefit patients with PAH associated with HIV infection, and that endothelin is an important pathogenic mediator in this disease.

Adult↗
PubMed2004

Changes in mitochondrial DNA in peripheral blood mononuclear cells from HIV-infected patients with lipoatrophy randomized to receive abacavir.

It has been suggested that lipoatrophy associated with exposure to nucleoside analogues is caused by depletion of mitochondrial DNA (mtDNA). The aim of the present study was to determine whether switching treatment from a thymidine analogue to abacavir was associated with an increase in the mtDNA copy number in peripheral blood mononuclear cells (PBMCs). Of 111 patients with lipoatrophy who were randomized to have treatment switched to abacavir or to continue treatment with thymidine analogues, 94 patients had PBMCs obtained at baseline and at weeks 4, 12, and 24, for quantification of the mtDNA copy number. During the 24-week study, there was no significant change in mtDNA copy numbers in PBMCs in either treatment group, despite improvement in peripheral lipoatrophy among patients whose treatment was switched to abacavir.

Anti-HIV Agents↗
PubMed2004

Three-year durability of dual-nucleoside versus triple-nucleoside therapy in a Thai population with HIV infection.

We compared the long-term immunologic and virologic efficacy of the dual- and triple-nucleoside therapy for HIV infection. This was a retrospective analysis of 2 randomized clinical trials in antiretroviral-naive patients. In the dual-nucleoside group, 15 started with didanosine (ddI) monotherapy and then added stavudine (d4T) after 24 weeks, 63 started with various doses of d4T and ddI, and 53 started with zidovudine (ZDV) and lamivudine (3TC). In the triple-nucleoside group, 53 started with ZDV, 3TC, and ddI. After 48 weeks, patients who were not failing were randomized to immediate (before treatment failure) versus delayed (at the time of virologic failure) switching from ddI and d4T to ZDV and 3TC or vice versa and from ZDV, 3TC, and ddI to d4T, 3TC, and abacavir (ABC). Failure was defined as a plasma HIV-1 RNA level>or=1 log10 above nadir or >or=10,000 copies/mL when nadir was <500 copies/mL. Patients failing therapy before week 48 received the new treatment as in the immediate switching group. Hydroxyurea was added to the last treatment regimen if patients failed after week 96. CD4 count and plasma HIV-1 RNA level (branched DNA assay with a cutoff point of 50 copies/mL) at week 144 were analyzed by intention to treat. Compared with the dual-nucleoside group, the triple-nucleoside group had a higher proportion of patients with <50 copies/mL at 144 weeks (60% vs. 18%; P<0.001), higher median CD4 count (388 cells/microL vs. 346 cells/microL; P=0.018), and longer duration of response, defined as the time from onset of viral suppression (<500 copies/mL) to the time of treatment failure (the first of 2 consecutive HIV-1 RNA measurements >500 copies/mL never followed by 2 consecutive visits showing suppressible viremia to <500 copies/mL) or discontinuation from the study (144 weeks vs. 104 weeks; P=0.002). Multivariate regression analyses showed that significant predictors for treatment success, defined as a plasma viral load <50 copies/mL at week 144, were asymptomatic clinical status at enrollment, a baseline plasma viral load <or=30,000 copies/mL, treatment with triple nucleosides, and a viral load response of <500 copies/mL by week 12. Triple-nucleoside therapy with ZDV, 3TC, and ddI or d4T, 3TC, and ABC in patients with HIV infection is more effective in inducing a sustained virologic response than the dual combinations of ZDV and 3TC or ddI and d4T.

Adult↗
PubMed2004

Impact of viral hepatitis co-infection on response to antiretroviral therapy and HIV disease progression in the HIV-NAT cohort.

OBJECTIVE: To examine the impact of viral hepatitis co-infection on HIV disease outcomes following commencement of combination antiretroviral therapy in a developing country setting. METHODS: HIV RNA suppression, CD4 cell count recovery, and HIV disease progression were examined within a cohort of Thai HIV-infected patients enrolled in eight HIV-NAT randomized controlled trials of antiretroviral therapy (n = 692). Hepatitis B virus (HBV) and hepatitis C virus (HCV) testing was performed on stored serum. RESULTS: Mean age was 32.3 years, 52% were male, 11% had CDC category C HIV disease at baseline, and 22% had received prior antiretroviral therapy. Prevalence of HBV, HCV and HBV/HCV co-infection was 8.7, 7.2 and 0.4%, respectively. Median HIV RNA reductions (log10 copies/ml) were approximately 1.5 for HIV, HIV-HBV, HIV-HCV subgroups from week 4 up to week 48. Mean increases in CD4 cell count were significantly lower among HIV-HBV and HIV-HCV subgroups at week 4 (HIV, 62 x 10(6) cells/l; HIV-HBV, 29 x 10(6) cells/l; HIV-HCV, 33 x 10(6) cells/l), however, by week 48 CD4 cell increases were similar (HIV, 115 x 10(6) cells/l; HIV-HBV, 113 x 10(6) cells/l; HIV-HCV, 97 x 10(6) cells/l). Cox regression analyses showed that HIV-HBV or HIV-HCV co-infection were not associated with a CD4 cell count increase of 100 x 10(6) cells/l over 48 weeks. Estimated progression to AIDS event or death at week 48 was 3.3% (95% confidence interval, 2.0-5.1%) for HIV, 6.7% (2.5-14.6%) for HIV-HBV, and 8.0% (2.2-20.5%) for HIV-HCV subgroups (P > 0.05). CONCLUSIONS: An early delayed CD4 count recovery among HIV/viral hepatitis co-infected patients was not sustained, and was not associated with increased HIV disease progression.

AIDS-Related Opportunistic Infections↗
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↗