Health economic outcomes of a minimal monitoring approach to providing HCV therapy.

Background: The ACTG A5360 trial demonstrated that HCV treatment without planned on-treatment monitoring is safe and effective. We report the health economic outcomes of MINMON.

Methods: A5360 was a 5-country, single-arm trial providing sofosbuvir/velpatasvir to people with HCV infection with no planned clinic visits between treatment initiation and week 24 sustained virologic response (SVR) evaluation.

Pharmacogenetic interactions of efavirenz or rifampin and isoniazid with levonorgestrel emergency contraception during treatment of HIV or tuberculosis.

Objective: In AIDS Clinical Trials Group study A5375, a pharmacokinetic trial of levonorgestrel emergency contraception, double-dose levonorgestrel (3 mg, versus standard dose 1.5 mg) offset the induction effects of efavirenz or rifampin on plasma levonorgestrel exposure over 8 h post-dose (AUC 0-8h ). We characterized the pharmacogenetics of these interactions.

Pharmacokinetics of dose-adjusted levonorgestrel emergency contraception combined with efavirenz-based antiretroviral therapy or rifampicin-containing tuberculosis regimens.

Objectives: To determine if double-dose levonorgestrel emergency contraception (EC) in combination with efavirenz or rifampicin, 2 drugs known to decrease levonorgestrel exposure, resulted in similar pharmacokinetics compared to standard-dose levonorgestrel EC without drug-drug interactions.

Study Design: We conducted a phase 2, open-label, multicenter, partially randomized, 4 parallel group trial in pre-menopausal females ≥16 years old without an indication for EC and not on hormonal contraception. Participants on dolutegravir-based antiretroviral therapy (ART) received levonorgestrel 1.

The Association Between Weight Gain, Sex, and Immune Activation Following the Initiation of Antiretroviral Therapy.

Background: Immune activation persists despite suppressive antiretroviral therapy (ART) and may be affected by sex or body composition. We explored these relationships in a subset of participants who initiated ART in two large randomized trials.

Methods: Purposeful sampling selected participants who achieved virologic suppression on ART and either maintained weight within ± 0.

Characteristics of REPRIEVE Trial Participants Identifying Across the Transgender Spectrum.

Because persons who identify across the transgender spectrum (PATS) are a key population in human immunodeficiency virus (HIV) yet are underreported in HIV and cardiovascular research, we aimed to characterize this population within the REPRIEVE global clinical trial (n = 7770). Acceptance of gathering gender identity was high (96%). Participation by PATS was 1.

Hepatitis C Virus (HCV) Direct-Acting Antiviral Therapy in Persons With Human Immunodeficiency Virus-HCV Genotype 1 Coinfection Resulting in High Rate of Sustained Virologic Response and Variable in Normalization of Soluble Markers of Immune Activation.

Background: Hepatitis C virus (HCV) direct-acting antivirals are highly effective. Less is known about changes in markers of immune activation in persons with human immunodeficiency virus (HIV) in whom a sustained virologic response (SVR) is achieved.

Methods: We conducted a nonrandomized clinical trial of 12 or 24 weeks of paritaprevir-ritonavir-ombitasvir plus dasabuvir (PrOD) with or without ribavirin in persons with HCV-1/HIV coinfection suppressed with antiretroviral therapy.

Intrahepatic Viral Kinetics During Direct-Acting Antivirals for Hepatitis C in Human Immunodeficiency Virus Coinfection: The AIDS Clinical Trials Group A5335S Substudy.

Background: Direct-acting antivirals (DAAs) targeting hepatitis C virus (HCV) have revolutionized outcomes in human immunodeficiency virus (HIV) coinfection.

Methods: We examined early events in liver and plasma through A5335S, a substudy of trial A5329 (paritaprevir/ritonavir, ombitasvir, dasabuvir, with ribavirin) that enrolled chronic genotype 1a HCV-infected persons coinfected with suppressed HIV: 5 of 6 treatment-naive enrollees completed A5335S.

Results: Mean baseline plasma HCV ribonucleic acid (RNA) = 6.

Screening and Enrollment by Sex in Human Immunodeficiency Virus Clinical Trials in the United States.

Background: Women are underrepresented in human immunodeficiency virus (HIV) research in the United States. To determine if women screening for HIV clinical trials enrolled at lower rates than men, we performed a retrospective, cross-trial analysis.

Methods: We conducted an analysis of screening and enrollment during 2003-2013 to 31 clinical trials at 99 AIDS Clinical Trials Group network research sites in the United States.

Long-term Outcomes in a Large Randomized Trial of HIV-1 Salvage Therapy: 96-Week Results of AIDS Clinical Trials Group A5241 (OPTIONS).

Background: Short-term (48-week) results of the OPTIONS trial showed that nucleoside reverse transcriptase inhibitors (NRTIs) can be safely omitted from salvage therapy as long as the regimen has a cumulative activity of >2 active antiretroviral medications. The long-term durability of this approach and outcomes in persons who have more-extensive HIV-1 drug resistance are uncertain.

Methods: Participants with virologic failure and anticipated antiretroviral susceptibility received an optimized regimen and were randomized to omit or add NRTIs.

HIV-Infected Women Gain More Weight than HIV-Infected Men Following the Initiation of Antiretroviral Therapy.

Background: Obesity is prevalent among HIV-infected individuals on antiretroviral therapy (ART). Cross-sectional studies have suggested that HIV-infected women are more likely to be overweight than men, but observational studies evaluating sex differences in body mass index (BMI) increases following ART initiation are conflicting.

Materials And Methods: We pooled data from three randomized clinical trials of ART initiation in persons with HIV in the United States.

Predictors of late virologic failure after initial successful suppression of HIV replication on efavirenz-based antiretroviral therapy.

Background: Practical issues, including cost, hinder implementing virologic monitoring of patients on antiretroviral therapy (ART) in resource-limited settings. We evaluated factors that might guide monitoring frequency and efforts to prevent treatment failure after initial virologic suppression.

Methods: Participants were the 911 HIV-infected antiretroviral-naïve adults with CD4 count <300 cells/μL who started efavirenz-based ART in the international A5175/PEARLS trial and achieved HIV-1 RNA <1000 copies/mL at 24 weeks.

Pharmacogenetics of unboosted atazanavir in HIV-infected individuals in resource-limited settings: a sub-study of the AIDS Clinical Trials Group (ACTG) PEARLS study (NWCS 342).

Objectives: The multinational PEARLS (ACTG A5175) study, conducted mainly in resource-limited settings, identified an increased treatment failure rate among HIV-infected individuals randomized to once-daily unboosted atazanavir, didanosine-EC, and emtricitabine compared with efavirenz-based regimens. We evaluated associations between selected human genetic polymorphisms and atazanavir pharmacokinetics in PEARLS.

Methods: Polymorphisms in CYP3A5, ABCB1, SLCO1B1 and NR1I2 were genotyped in PEARLS participants randomized to atazanavir plus didanosine-EC plus emtricitabine in Peru, South Africa and the USA, who also consented to genetic analysis.

HIV Salvage Therapy Does Not Require Nucleoside Reverse Transcriptase Inhibitors: A Randomized, Controlled Trial.

Background: Nucleoside reverse transcriptase inhibitors (NRTIs) are often included in antiretroviral regimens in treatment-experienced patients in the absence of data from randomized trials.

Objective: To compare treatment success between participants who omit versus those who add NRTIs to an optimized antiretroviral regimen of 3 or more agents.

Design: Multicenter, randomized, controlled trial.

Presence of Plasmodium falciparum DNA in Plasma Does Not Predict Clinical Malaria in an HIV-1 Infected Population.

Background: HIV-1 and Plasmodium falciparum malaria cause substantial morbidity in Sub-Saharan Africa, especially as co-infecting pathogens. We examined the relationship between presence of P. falciparum DNA in plasma samples and clinical malaria as well as the impact of atazanavir, an HIV-1 protease inhibitor (PI), on P.

Differences in antiretroviral safety and efficacy by sex in a multinational randomized clinical trial.

Background And Objective: Worldwide, 50% of human immunodeficiency virus (HIV)-infected people are women. This study was to evaluate whether the safety and efficacy outcomes of three initial antiretroviral regimens (ARVs) differed by sex.

Methods: Antiretroviral regimen naive participants from nine countries in four continents were assigned to ARVs with efavirenz (EFV) plus lamivudine-zidovudine, atazanavir (ATV) plus didanosine (ddI)-EC/emtricitabine (FTC) or EFV plus FTC-tenofovir-DF.

Combination antiretroviral treatment for women previously treated only in pregnancy: week 24 results of AIDS clinical trials group protocol a5227.

Background: Women with HIV and prior exposure to combination antiretroviral therapy (cART) solely for prevention of mother-to-child transmission (pMTCT) need to know whether they can later be treated successfully with a commonly used regimen of efavirenz (EFV) and coformulated emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF).

Methods: Nonpregnant women with plasma HIV-1 RNA of ≥500 copies per milliliter, previously cART exposed for pMTCT only, were eligible if they were off ART for ≥24 weeks before entry, were without evidence of drug resistance on standard genotyping, and were ready to start EFV plus FTC/TDF. The primary endpoint was virologic response (defined as plasma HIV RNA <400 copies/mL) at 24 weeks.

Efficacy and safety of three antiretroviral regimens for initial treatment of HIV-1: a randomized clinical trial in diverse multinational settings.

Background: Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.

Methods And Findings: 1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF).

Detection of microbial translocation in HIV and SIV infection using the Limulus amebocyte lysate assay is masked by serum and plasma.

Objective: Microbial translocation (MT) is thought to be a major contributor to the pathogenesis of HIV-related immune activation, and circulating lipopolysaccharide (LPS) from gram-negative bacteria is the principle measurement of this process. However, related research has been impeded by inconsistent LPS test results.

Methods: Specimens were obtained from HIV-infected adults enrolled in the PEARLS study (ACTG A5175) and HIV-HCV co-infected participants enrolled in a study of liver disease staging using MRI elastography.

Prevalence and clinical associations of CXCR4-using HIV-1 among treatment-naive subtype C-infected women in Botswana.

HIV-1 coreceptor use was determined using a phenotypic assay in plasma samples from treatment-naive women infected with subtype C virus who had CD4 cell counts below 200 cells/mm3. Of 148 women, 14.9% were infected with dual/mixed virus; the remainder had R5 virus.

Hematologic and hepatic toxicities associated with antenatal and postnatal exposure to maternal highly active antiretroviral therapy among infants.

Objective: To assess hematologic and hepatic toxicities associated with in utero and breastfeeding exposure to maternal highly active antiretroviral therapy (HAART) among infants in Botswana.

Design: A nested cohort study within a randomized clinical trial (the Mashi Study). Laboratory toxicities among infants born to women who initiated HAART before delivery were compared with toxicities among those born to women who received zidovudine and a single dose of nevirapine or placebo in labor.

Response to antiretroviral therapy after a single, peripartum dose of nevirapine.

Background: A single dose of nevirapine during labor reduces perinatal transmission of human immunodeficiency virus type 1 (HIV-1) but often leads to viral nevirapine resistance mutations in mothers and infants.

Methods: We studied the response to nevirapine-based antiretroviral treatment among women and infants who had previously been randomly assigned to a single, peripartum dose of nevirapine or placebo in a trial in Botswana involving the prevention of the transmission of HIV-1 from mother to child. All women were treated with antenatal zidovudine.

Breastfeeding plus infant zidovudine prophylaxis for 6 months vs formula feeding plus infant zidovudine for 1 month to reduce mother-to-child HIV transmission in Botswana: a randomized trial: the Mashi Study.

Context: Postnatal transmission of human immunodeficiency virus-1 (HIV) via breastfeeding reverses gains achieved by perinatal antiretroviral interventions.

Objective: To compare the efficacy and safety of 2 infant feeding strategies for the prevention of postnatal mother-to-child HIV transmission.

Design, Setting, And Patients: A 2 x 2 factorial randomized clinical trial with peripartum (single-dose nevirapine vs placebo) and postpartum infant feeding (formula vs breastfeeding with infant zidovudine prophylaxis) interventions.

Maternal single-dose nevirapine versus placebo as part of an antiretroviral strategy to prevent mother-to-child HIV transmission in Botswana.

Background: Single-dose nevirapine given to women and infants reduces mother-to-child HIV transmission, but nevirapine resistance develops in a large percentage of women.

Objective: To determine whether the maternal nevirapine dose could be eliminated in the setting of zidovudine prophylaxis.

Design, Setting, And Participants: A 2 x 2 factorial, randomized, clinical trial, with a double-blinded peripartum factor designed to assess the equivalence of maternal single-dose nevirapine versus placebo with respect to HIV transmission.

Oxidant stress and peripheral neuropathy during antiretroviral therapy: an AIDS clinical trials group study.

Background: Peripheral neuropathy that complicates HIV nucleoside reverse transcriptase inhibitor (NRTI) therapy is likely caused by mitochondrial injury. Mitochondria play a central role in regulating oxidant stress. We explored the relationships between oxidant stress and NRTI-induced peripheral neuropathy.