Dataset Information

A randomized factorial trial comparing 4 treatment regimens in treatment-naive HIV-infected persons with AIDS and/or a CD4 cell count <200 cells/?L in South Africa.

ABSTRACT: BACKGROUND:Few randomized trials comparing antiretroviral therapy (ART) regimens have been conducted in resource-limited settings. METHODS:In the Republic of South Africa, antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals >14 years old with a CD4 cell count <200 cells/?L or a prior AIDS diagnosis were randomized to receive efavirenz (EFV) or lopinavir/ritonavir (LPV/r) with either zidovudine (ZDV) plus didanosine (ddI) or stavudine (d4T) plus lamivudine (3TC) in an open-label, 2-by-2 factorial study and followed up for the primary outcome of AIDS or death and prespecified secondary outcomes, including CD4 cell count and viral load changes, treatment discontinuation, and grade 4 events. RESULTS:In total, 1771 persons were randomized and followed up for a median of 24.7 months. AIDS or death occurred in (1) 163 participants assigned EFV and 157 assigned LPV/r (hazard ratio [HR], 1.04 [95% confidence interval {CI}, 0.84-1.30]) and in (2) 170 participants assigned ZDV+ddI and 150 assigned d4T+3TC (HR, 1.15 [95% CI, 0.93-1.44]). HIV RNA levels were lower (P < .001) and CD4 cell counts were greater (P < .01) over follow-up for d4T+3TC versus ZDV+ddI. Rates of potentially life-threatening adverse events and overall treatment discontinuation were similar for d4T+3TC and ZDV+ddI; however, more participants discontinued d4T because of toxicity (12.6%) than other treatments (<5%). CONCLUSION:EFV and LPV/r are effective components of first-line ART. The poorer viral and immune responses with ZDV+ddI and the greater toxicity-associated discontinuation rate with d4T+3TC suggest that these treatments be used cautiously as initial therapy. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT00342355.

SUBMITTER: Phidisa II Writing Team for Project Phidisa

PROVIDER: S-EPMC3008165 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A randomized factorial trial comparing 4 treatment regimens in treatment-naive HIV-infected persons with AIDS and/or a CD4 cell count <200 cells/μL in South Africa.

Ratsela Andrew A Polis Michael M Dhlomo Sibongiseni S Emery Sean S Grandits Greg G Khabo Paul P Khanyile Thandeka T Komati Stephanus S Neaton James D JD Naidoo Lionel Chris David LC Magongoa Daphne D Qolohle Duma D

The Journal of infectious diseases 20101013 10

<h4>Background</h4>Few randomized trials comparing antiretroviral therapy (ART) regimens have been conducted in resource-limited settings.<h4>Methods</h4>In the Republic of South Africa, antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals >14 years old with a CD4 cell count <200 cells/μL or a prior AIDS diagnosis were randomized to receive efavirenz (EFV) or lopinavir/ritonavir (LPV/r) with either zidovudine (ZDV) plus didanosine (ddI) or stavudine (d4T) plus lamivudine ...[more]

PMID: 20942650

Similar Datasets

Project description:BACKGROUND:The effect of drug resistance transmission on disease progression in the newly infected patient is not well understood. Major drug resistance mutations severely impair viral fitness in a drug free environment, and therefore are expected to revert quickly. Compensatory mutations, often already polymorphic in wild-type viruses, do not tend to revert after transmission. While compensatory mutations increase fitness during treatment, their presence may also modulate viral fitness and virulence in absence of therapy and major resistance mutations. We previously designed a modeling technique that quantifies genotypic footprints of in vivo treatment selective pressure, including both drug resistance mutations and polymorphic compensatory mutations, through the quantitative description of a fitness landscape from virus genetic sequences. RESULTS:Genotypic correlates of viral load and CD4 cell count were evaluated in subtype B sequences from recently diagnosed treatment-naive patients enrolled in the SPREAD programme. The association of surveillance drug resistance mutations, reported compensatory mutations and fitness estimated from drug selective pressure fitness landscapes with baseline viral load and CD4 cell count was evaluated using regression techniques. Protease genotypic variability estimated to increase fitness during treatment was associated with higher viral load and lower CD4 cell counts also in treatment-naive patients, which could primarily be attributed to well-known compensatory mutations at highly polymorphic positions. By contrast, treatment-related mutations in reverse transcriptase could not explain viral load or CD4 cell count variability. CONCLUSIONS:These results suggest that polymorphic compensatory mutations in protease, reported to be selected during treatment, may improve the replicative capacity of HIV-1 even in absence of drug selective pressure or major resistance mutations. The presence of this polymorphic variation may either reflect a history of drug selective pressure, i.e. transmission from a treated patient, or merely be a result of diversity in wild-type virus. Our findings suggest that transmitted drug resistance has the potential to contribute to faster disease progression in the newly infected host and to shape the HIV-1 epidemic at a population level.

Project description:BackgroundComplete recovery of the CD4 T cell count is uncommon among chronically HIV-infected individuals with very low pre-treatment CD4 count. We studied the prevalence of chronically immune recovery and its associated factors including immune characteristics chronic HIV-infected Thais.MethodsTreatment-naïve participants (n = 375) from the HIV-NAT 006 cohort with a pre-treatment CD4 T cell count after initiating antiretroviral therapy (ART) and having achieved a suppressed viremia (HIV-RNA level < 400 copies/mL) were retrospectively followed at the Thai Red Cross AIDS Research Centre, Bangkok, Thailand. Suboptimal immune recovery (SIR) was defined as having a CD4+ T cell count <200 cells/mm3 for 3 years after ART initiation. A case-control sub-study matched for age, sex and pre-ART CD4 T cell count was conducted to compare immunological characteristics between SIR (n = 17) and non-SIR (n = 24) participants. Immunological biomarkers such as interleukin-7 (IL-7) and soluble CD14 (sCD14) and other covariates including cytomegalovirus (CMV) DNA level, baseline hemoglobin level, hepatitis B and C co-infections, and T cell subsets associated with immune activation and exhaustion were evaluated.ResultsAmong 375 participants with pre-ART CD4 T cell counts < 200 cells/mm3, the prevalence of SIR was 39.7%, 19.7% and 7.7% at years 1, 2 and 3 after starting ART, respectively. In a multivariate analysis, a pre-ART CD4 T cell count ≤100 cells/mm3 (adjusted odds ratio [aOR] 9.45, 95% CI 2.92-30.61, p < 0.001), older age (aOR 1.07, 95% CI 1.01-1.13, p = 0.029) and baseline HIV-RNA level (aOR 0.36, 95% CI 0.21-0.59, p < 0.001) were independently associated with SIR at year 3 after ART initiation. In the matched case-control sub-study (cases = 17, controls = 24), there was a higher prevalence of hepatitis C co-infection (18.8% vs. 0%, p = 0.05), lower sCD14 levels (mean, 6.23 vs. 6.27 log10 pg/mL, p = 0.04), lower CD8 T cell counts (mean, 514 vs. 876, p = 0.0003), lower CD4/CD8 T cell ratio (mean, 0.27 vs. 0.41, p = 0.01) and higher expression of PD1 on CD8+ T cells (74.2% vs. 65.1%, p = 0.02) observed in SIR participants compared to their non-SIR counterparts at year 3 after ART initiation.ConclusionsNearly 10% of the study participants who had achieved virological suppression failed to recover a CD4 T cell count > 200 cells/mm3 after 3 years of ART which was with a very low pre-ART CD4 T cell count and older age. The long-term clinical outcomes of SIR participants need to be further explored.

Project description:Recently approved, interferon-free medication regimens for treating hepatitis C are highly effective, but extremely costly. We aimed to identify cost-effective strategies for managing treatment-naïve U.S. veterans with new hepatitis C medication regimens. We developed a Markov model with 1-year cycle length for a cohort of 60-year-old veterans with untreated genotype 1 hepatitis C seeking treatment in a typical year. We compared using sofosbuvir/ledipasvir or ombitasvir/ritonavir/paritaprevir/dasabuvir to treat: (1) any patient seeking treatment; (2) only patients with advanced fibrosis or cirrhosis; or (3) patients with advanced disease first and healthier patients 1 year later. The previous standard of care, sofosbuvir/simeprevir or sofosbuvir/pegylated interferon/ribavirin, was included for comparison. Patients could develop progressive fibrosis, cirrhosis, or hepatocellular carcinoma, undergo transplantation, or die. Complications were less likely after sustained virological response. We calculated the incremental cost per quality-adjusted life year (QALY) and varied model inputs in one-way and probabilistic sensitivity analyses. We used the Veterans Health Administration perspective with a lifetime time horizon and 3% annual discounting. Treating any patient with ombitasvir-based therapy was the preferred strategy ($35,560; 14.0 QALYs). All other strategies were dominated (greater costs/QALY gained than more effective strategies). Varying treatment efficacy, price, and/or duration changed the preferred strategy. In probabilistic sensitivity analysis, treating any patient with ombitasvir-based therapy was cost-effective in 70% of iterations at a $50,000/QALY threshold and 65% of iterations at a $100,000/QALY threshold.Managing any treatment-naïve genotype 1 hepatitis C patient with ombitasvir-based therapy is the most economically efficient strategy, although price and efficacy can impact cost-effectiveness. It is economically unfavorable to restrict treatment to patients with advanced disease or use a staged treatment strategy. (Hepatology 2016;63:428-436).

Dataset Information

A randomized factorial trial comparing 4 treatment regimens in treatment-naive HIV-infected persons with AIDS and/or a CD4 cell count <200 cells/?L in South Africa.

Publications

A randomized factorial trial comparing 4 treatment regimens in treatment-naive HIV-infected persons with AIDS and/or a CD4 cell count <200 cells/μL in South Africa.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure