OBJECTIVES:

To describe the validation of a sensitive high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) method allowing the simultaneous quantification of darunavir (DRV) and etravirine (ETR) in peripheral blood mononuclear cells (PBMCs) and its application in a cohort of HIV-1 infected patients.

METHODS:

Blood samples were obtained from 110 patients. PMBCs were isolated using density gradient centrifugation. Drug extraction from PBMCs was performed with a 60:40 methanol-water (MeOH-H2O) solution containing deuterated IS (DRV-d9 and ETR-d8). The chromatographic separation was performed on a RP18 XBridge™ column.

RESULTS:

The geometric mean (GM) of cell associated concentration ([DRV]CC) and plasmatic concentration ([DRV]plasma) were 360.5ng/mL (CI95%:294.5-441.2) and 1733ng/mL (CI95%:1486-2021), respectively. A geometric mean intracellular (IC)/plasma ratio (GMR) of 0.21 (CI95%:0.18-0.24) was calculated. Adjusted for dose/body surface area and post-intake time, a statistically significant correlation was observed between [DRV]Plasma and the eGFR (p=0.002) and between [DRV]Plasma and the concomitant use of ETR (p=0.038). For the 10 patients receiving ETR in addition to DRV, the GM of [ETR]Plasma (available for 8 out of 10 patients) and [ETR]CC were 492.3ng/mL and 2951ng/mL respectively. The GMR of ETR was 7.6 (CI95%: 3.61-13.83).

CONCLUSIONS:

A handy and sensitive high performance LC-MS/MS method allowing the simultaneous quantification of DRV and ETR in PBMCs has been described and successfully applied in the largest cohort of DRV-treated patients reported to date. ETR accumulates more efficiently in PBMCs compared to DRV. We have also highlighted a possible impact of ETR on DRV plasma concentrations requiring further investigations.

INTERVENTION:

Product Name: Darunavir/Cobicistat/Emtricitabine/Tenofovir alafenamide (D/C/F/TAF) FDC tablet (Placebo) Pharmaceutical Form: Film‐coated tablet Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use

CONDITION:

Human Immunodeficiency Virus Type 1 ; MedDRA version: 20.1 Level: LLT Classification code 10068341 Term: HIV‐1 infection System Organ Class: 100000004862 Therapeutic area: Diseases [C] ‐ Virus Diseases [C02]

PRIMARY OUTCOME:

; Secondary Objective: The secondary objectives are: ; • To assess the acceptability of swallowing the scored film coated D/C/F/TAF FDC tablet, taken as a whole tablet and as a split tablet; • To assess the acceptability of the intake of the scored film‐coated D/C/F/TAF FDC tablet, if to be taken daily as a whole tablet and as a; split tablet.; • To assess the ease of splitting the scored film‐coated D/C/F/TAF FDC tablet.; Main Objective: The primary objective is to assess the ability to swallow the scored film‐coated D/C/F/TAF FDC tablet, irrespective of the mode of intake. Primary end point(s): 1. The ability to swallow the tablet, irrespective of the mode of intake. Timepoint(s) of evaluation of this end point: 1. Day 1

SECONDARY OUTCOME:

; Secondary end point(s): 1. A 3‐point questionnaire to assess the acceptability of the intake of the ; whole tablet and as a split tablet by the participant and by the caregiver. ; 2. A 3‐point questionnaire to assess the acceptability of the intake of the ; whole tablet and as a split tablet by the participant, if to be taken daily. ; 3. A 3‐point questionnaire to assess the ease of splitting the tablet by ; the participant's caregiver. ; 4. A questionnaire to assess the swallowing difficulties as reported by ; the observer. ; 5. Assessment of adverse events (AEs).; ; Timepoint(s) of evaluation of this end point: 1 to 6: Within 15 minutes after each observed intake and before next intake ; 7: Throughout the study;

INCLUSION CRITERIA:

Each potential participant must satisfy all of the following criteria to be enrolled in the study: 1. Male or female. 2. =6 to <12 years of age. 3. Have a body weight of at least 25 kg and less than 40 kg. 4. Has documented chronic HIV‐1 infection. 5. Must be on a stable ARV regimen for at least 3 months prior to screening. 6. Has documented plasma HIV‐1 ribonucleic acid (RNA) <400 copies/mL within 6 months prior to screening. 7. Parent(s) (preferably both if available or as per local requirements) or their legally acceptable representative must sign an ICF indicating that he or she understands the purpose of, and procedures required for, the study and is willing to allow the child to participate in the study. Assent is also required of children capable of understanding the nature of the study (typically 7 ye

INTERVENTION:

Product Code: GS‐9883/F/TAF Pharmaceutical Form: Film‐coated tablet INN or Proposed

INN:

GS‐9883 Current Sponsor code: GS‐9883 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 50‐ INN or Proposed

INN:

EMTRICITABINE CAS Number: 143491‐57‐0 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200‐ INN or Proposed

INN:

Tenofovir Alafenamide CAS Number: 379270‐37‐8 Other descriptive name: TENOFOVIR ALAFENAMIDE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 25‐

CONDITION:

Human Immunodeficiency Virus (HIV‐1) Infection ; MedDRA version: 18.1 Level: LLT Classification code 10068341 Term: HIV‐1 infection System Organ Class: 100000004862 Therapeutic area: Diseases [C] ‐ Virus Diseases [C02]

PRIMARY OUTCOME:

Main Objective: To evaluate the efficacy of switching to a FDC of GS‐9883/F/TAF versus continuing on a regimen consisting of boosted atazanavir or darunavir plus either FTC/TDF or ABC/3TC in HIV‐1 infected adult subjects who are virologically suppressed as determined by the proportion of subjects with virologic failure (HIV‐1 RNA >= 50 copies/mL) at Week 48 Primary end point(s): The proportion of subjects with virologic failure (HIV‐1 RNA >= 50 copies/mL) at Week 48 as defined by the modified US FDA snapshot algorithm Secondary Objective: To evaluate the safety and tolerability of the two treatment groups through Week 48 Timepoint(s) of evaluation of this end point: Week 48

SECONDARY OUTCOME:

Secondary end point(s): ‐ The proportion of subjects with HIV‐1 RNA < 50 copies/mL at Week 48 as defined by the US FDA snapshot algorithm; ; ‐ The change from baseline in CD4+ cell counts at Week 48 Timepoint(s) of evaluation of this end point: Week 48

INCLUSION CRITERIA:

1) The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures 2) Aged 18 years or older 3) Currently receiving antiretroviral regimen consisting of ritonavir or cobicistat boosted ATV or DRV plus either FTC/TDF or ABC/3TC for 6 months or more preceding the screening visit 4) HIV RNA < 50 copies/mL at the screening visit 5) Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant) 6) Adequate renal function 7) Hepatic transaminases (AST and ALT) <= 5 x upper limit of normal (ULN) 8) Total bilirubin <= 1.5 mg/dL (<= 26 umol/L), or normal direct bilirubin 9) Adequate hematologic function (absolute neutrophil count >= 750/mm3 (>= 0.75 GI/L); platelets >= 50,000/mm3 (>= 50 GI/L); hemoglobin >= 8.5 g/dL (>= 85 g/L)) 10) Serum amylase <= 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible if serum lipase is <= 5 × ULN)<br

Background: Randomised comparative data on efficacy and safety of second-line antiretroviral therapy (ART) after failure of non-nucleoside reverse transcriptase inhibitors (NNRTIs) across diverse geographical settings are scarce. The aim of this study was to evaluate optimal second-line ART for people with HIV. Methods: D2EFT is a completed international, randomised, open-label, phase 3b/4 trial evaluating three second-line ART strategies in adults (aged ≥18 years) with HIV-1 for whom first-line NNRTI therapy has failed. The study was done at 28 sites across 14 countries in Asia, Africa, and Latin America. It was originally designed to compare recommended standard of care (ritonavir-boosted darunavir [800 mg darunavir plus 100 mg ritonavir once daily] plus two nucleoside reverse transcriptase inhibitors [NRTIs; dosed once or twice daily]) with a novel nucleoside sparing regimen of dolutegravir (50 mg once daily) with ritonavir-boosted darunavir. The study was adapted during the first year to add a third arm of dolutegravir (50 mg once daily) with fixed tenofovir disoproxil fumarate (300 mg once daily) plus either lamivudine (300 mg once daily) or emtricitabine (200 mg once daily). Participants were randomly assigned with a computer-generated, blocked randomisation scheme (block size of two) stratified by site, previous tenofovir disoproxil fumarate use, and HIV viral load. The trial was designed to evaluate non-inferiority of either interventional arm against standard of care for the primary outcome of virological suppression, as determined by HIV RNA load of less than 50 copies per mL at 48 weeks. The prespecified non-inferiority margin was 12%. Comparisons were made with a modified intention-to-treat population, including all participants randomly assigned but excluding administrative withdrawals. This study is registered with ClinicalTrials.gov, NCT03017872. Findings: 1190 individuals were screened; 828 participants were enrolled between Nov 1, 2017, and Dec 31, 2021. Two participants were unable to receive their assigned regimen for administrative reasons; and 826 participants were included in analyses. Median age was 39 years (IQR 33–46), and 450 (54%) participants were female. Baseline median CD4 count was 206 cells per μL (23–354) and median HIV RNA was 15 400 copies per mL (3600–65 986). The proportion of participants with HIV RNA of less than 50 copies per mL at 48 weeks was 194 (75%) of 257 in the ritonavir-boosted darunavir plus two NRTIs group, 222 (84%) of 264 in the ritonavir-boosted darunavir plus dolutegravir group, and 227 (78%) of 291 in the dolutegravir with tenofovir disoproxil fumarate plus either lamivudine or emtricitabine group. Compared with ritonavir-boosted darunavir plus two NRTIs, the difference in virological suppression was 8·6% (95% CI 1·7 to 15·5; p=0·016) for dolutegravir plus ritonavir-boosted darunavir and 6·7% (–1·2 to 14·4; p=0·093) for dolutegravir with tenofovir disoproxil fumarate plus either lamivudine or emtricitabine. Six deaths occurred, none of which were related to treatment. 19 pregnancies (11 livebirths) occurred with no congenital defects. Interpretation: In individuals experiencing failure of an NNRTI-based first-line ART, a switch to either dolutegravir plus ritonavir-boosted darunavir or dolutegravir with tenofovir disoproxil fumarate plus either lamivudine or emtricitabine, without universal access to genotyping, was non-inferior in achieving viral suppression compared with ritonavir-boosted darunavir plus two NRTIs. These global data support the most recent WHO treatment guidelines. Funding: UNITAID; National Institute of Allergy and Infectious Diseases, USA; National Health and Medical Research Council, Australia; ViiV Healthcare; and Janssen.

INTERVENTION:

Trade Name: REYATAZ 300 mg cápsulas duras Pharmaceutical Form: Capsule, hard INN or Proposed

INN:

ATAZANAVIR Other descriptive name: ATAZANAVIR Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 300‐ Trade Name: PREZISTA 400 mg comprimidos recubiertos con película Pharmaceutical Form: Film‐coated tablet INN or Proposed

INN:

DARUNAVIR ETANOLATO Other descriptive name: DARUNAVIR ETANOLATO Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 400‐

CONDITION:

Tratamiento para pacientes infectados por el VIH‐1 sin tratamiento previo ; MedDRA version: 13 Level: LLT Classification code 10020160 Term: Enfermedad por

VIH PRIMARY OUTCOME:

Main Objective: Comparar el efecto sobre los niveles de colesterol total entre las dos ramas de tratamiento a las 24 semanas de seguimiento Primary end point(s): Comparar la diferencia respecto al basal de los niveles de colesterol total entre las dos ramas de tratamiento a las 24 semanas de seguimiento. Secondary Objective: Comparar el efecto entre las dos ramas de tratamiento sobre:; 1. Perfil lipídico; 2. Riesgo cardiovascular; 3. Metabolismo de la glucosa; 4. Biomarcadores inflamatorios y anti‐inflamatorios; 5. Actividad antiviral; 6. Recuento de células CD4; 7. Seguridad y tolerabilidad; 8. Cambios en la composición corporal

INCLUSION CRITERIA:

1. Pacientes de ambos sexos* de edad igual o superior a 18 años 2. Diagnóstico de infección por VIH‐1 (según criterios diagnósticos estándar) 3. No tratados previamente con ningún fármaco antrretroviral 4. Carga viral plasmática 1000 copias/ml 5. Pacientes clínicamente estables en opinión del investigador en el momento de la inclusión 6. Capaces de cumplir el calendario de visitas del estudio y otros requisitos del protocolo 7. Que, adecuadamente informados, otorguen su consentimiento por escrito para participar en el estudio y someterse a las pruebas y exploraciones que ello comporta *Las mujeres en edad fértil deben comprometerse a la abstinencia sexual o a la utilización de métodos anticonceptivos de barrera durante el estudio. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes<

Background: Simplified regimens with reduced pill burden and fewer side-effects are desirable for people living with HIV. We investigated the efficacy and safety of switching to a single-tablet regimen of darunavir, cobicistat, emtricitabine, and tenofovir alafenamide versus continuing a regimen of boosted protease inhibitor, emtricitabine, and tenofovir disoproxil fumarate. Methods: EMERALD was a phase-3, randomised, active-controlled, open-label, international, multicentre trial, done at 106 sites across nine countries in North America and Europe. HIV-1-infected adults were eligible to participate if they were treatment-experienced and virologically suppressed (viral load <50 copies per mL for ≥2 months; one viral load of 50–200 copies per mL was allowed within 12 months before screening), and patients with a history of virological failure on non-darunavir regimens were allowed. Randomisation was by computer-generated interactive web-response system and stratified by boosted protease inhibitor use at baseline. Patients were randomly assigned (2:1) to switch to the open-label study regimen or continue the control regimen. The study regimen consisted of a fixed-dose tablet containing darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg, which was taken once per day for 48 weeks. The primary outcome was the proportion of participants with virological rebound (confirmed viral load ≥50 copies per mL or premature discontinuations, with last viral load ≥50 copies per mL) cumulative through week 48; we tested non-inferiority (4% margin) of the study regimen versus the control regimen in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT02269917. Findings: The study began on April 1, 2015, and the cutoff date for the week 48 primary analysis was Feb 24, 2017. Of 1141 patients (763 in the study group and 378 in the control group), 664 (58%) had previously received five or more antiretrovirals, including screening antiretrovirals, and 169 (15%) had previous virological failure on a non-darunavir regimen. The study regimen was non-inferior to the control for virological rebound cumulative through week 48 (19 [2·5%] of 763 patients in the study group vs eight (2·1%) of 378 patients in the control group; difference 0·4%, 95% CI −1·5 to 2·2; p<0·0001). No resistance to any study drug was observed. Numbers of discontinuations related to adverse events (11 [1%] of 763 patients in the study group vs four [1%] of 378 patients in the control group) and grade 3–4 adverse events (52 [7%] patients vs 31 [8%] patients) were similar between the two groups. There was a small non-clinically relevant but statistically significant (0·2 [SD 1·1] vs 0·1 [1·1], p=0.010) difference between the two groups in change from baseline in total cholesterol to HDL-cholesterol ratio. Only one serious adverse event (pancreatitis in the study group) was deemed as possibly related to the study regimen. Interpretation: Our findings show the safety and efficacy of single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide as a potential switch option for the treatment of HIV-1 infection in adults with viral suppression. Funding: Janssen. © 2018 Elsevier Ltd

The purpose of this study is to determine the pharmacokinetic profile of TMC125 400mg with tenofovir DF/emtricitabine FDC (fixed dose combination) 300/200mg all dosed once daily with and without darunavir/ritonavir 800/100 mg once daily in HIV-1 infected, antiretroviral (ARV) naÃ-ve patients (patients who have never received ARV treatment).

INTERVENTION:

Product Name: TMC114 ethanolate Product Code: TMC114 Pharmaceutical Form: Film‐coated tablet INN or Proposed

INN:

darunavir CAS Number: 206361‐99‐1 Current Sponsor code: TMC114 (F032) Other descriptive name: TMC114 ethanolate Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 600‐ Product Name: TMC114 ethanolate Product Code: TMC114 Pharmaceutical Form: Film‐coated tablet INN or Proposed

INN:

darunavir CAS Number: 206361‐99‐1 Current Sponsor code: TMC114 (F030) Other descriptive name: TMC114 ethanolate Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 400‐ Trade Name: Norvir Product Name: Norvir Pharmaceutical Form: Capsule, soft INN or Proposed

INN:

ritonavir CAS Number: 155213‐67‐5 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐

CONDITION:

HIV‐1 ; MedDRA version: 9.1 Level: LLT Classification code 10020161 Term: HIV infection

INCLUSION CRITERIA:

Subjects who meet all of the following criteria are eligible for this trial. 1. Male or female subjects, aged 18 years or older. 2. Subjects with documented HIV‐1 infection. 3. Stable HAART regimen for at least 12 weeks at screening. Note: HAART is defined as potent anti‐HIV treatment usually including a combination of 3 or more drugs with activity against HIV whose purpose is to reduce viral load to undetectable. This regimen usually includes treatment with at least 2 NRTIs in combination with at least 1 additional ARV from the NNRTI and/or PIs classes or a combination of 3 NRTIs. 4. In the investigator’s opinion, NNRTIs are not a valid treatment option, because of the subject’s ARV treatment history, ARV resistance testing, medication‐taking behavior, safety and tolerance concerns, or other patient‐related factors. 5. Prescreening or/and screening plasma HIV‐1 RNA > 1,000 copies/mL (assayed by RNA PCR standard specimen procedure) on

HAART PRIMARY OUTCOME:

Main Objective: MAIN PHASE; To demonstrate non‐inferiority in virologic response, defined as a confirmed plasma viral load of < 50 HIV‐1 RNA copies/mL at Week 48 (as defined by the TLOVR algorithm), with DRV/rtv 800/100 mg q.d. versus DRV/rtv 600/100 mg b.i.d. in early ARV‐experienced patients with a non‐inferiority margin (delta) of 12%, when administered in combination with an individually selected OBR.; ; EXTENSION PHASE AFTER WEEK 48; To provide DRV/rtv access as a 600/100 mg b.i.d. dosage via an extension phase of the TMC114‐TiDP31‐C229 trial to subjects who completed the 48 weeks of treatment with DRV/rtv in the main phase of the trial and continue to benefit from this treatment, and who live in a region where DRV is not yet commercially available, not yet reimbursed by the public and/or private health system or can not be accessed from another source (e.g., access program, government program). In addition, information on safety of DRV/rtv in combination with other ARVs will be monitored. Primary end point(s): Demonstration of non‐inferiority in virologic response Secondary Objective: The secondary objectives are:; ‐ to evaluate safety and tolerabilityover 48 weeks; ; ‐ to evaluate the durability of efficacy over 48 weeks;; ‐ to evaluate the change in viral load from baseline;; ‐ to evaluate the percentage subjects with a confirmed plasma viral load < 400 HIV‐1 RNA copies/mL;; ‐ to evaluate the lipid effects of DRV/rtv q.d. versus b.i.d.;; ‐ to compare the immunologic response;; ‐ to evaluate resistance characteristics;; ‐ to evaluate DRV and ritonavir pharmacokinetics following q.d. and b.i.d. dosing and explore the PK/PD relationship between: 1) DRV and efficacy/safety and 2) ritonavir and safety for b.i.d. and q.d. regimens;; ‐ to determine and compare the subject‐reported antiretroviral (ARV) medication adherence in subjects treated with DRV/rtv 800/100 mg q.d. versus DRV/rtv 600/100 b.i.d., both administered in combination with an individually selected OBR, at baseline and over 48 weeks.

BACKGROUND:

Integrase inhibitor (INSTI) with boosted darunavir (DRV/r), a regimen with a high-resistance barrier, avoiding NRTI toxicities, might be a switching option in children living with HIV (CLWHIV).

METHODS:

SMILE is a randomised non-inferiority trial evaluating safety and antiviral efficacy of once-daily INSTI + DRV/r vs. continuing on current standard-of-care (SOC) triple ART (2NRTI + boosted PI/NNRTI) in virologically-suppressed CLWHIV aged 6-18 years. The primary outcome is the proportion with confirmed HIV-RNA ≥50 copies/mL by week 48, estimated by Kaplan-Meier method. Non-inferiority margin was 10%. Registration number for SMILE are: ISRCTN11193709, NCT #: NCT02383108.

FINDINGS:

Between 10th June 2016 and 30th August 2019, 318 participants were enrolled from Africa 53%, Europe 24%, Thailand 15% and Latin America 8%, 158 INSTI + DRV/r [153 Dolutegravir (DTG); 5 Elvitegravir (EVG)], 160 SOC. Median (range) age was 14.7 years (7.6-18.0); CD4 count 782 cells/mm3 (227-1647); 61% female. Median follow-up was 64.3 weeks with no loss to follow-up. By 48 weeks, 8 INSTI + DRV/r vs. 12 SOC had confirmed HIV-RNA ≥50 copies/mL; difference (INSTI + DRV/r-SOC) -2.5% (95% CI.: -7.6, 2.5%), showing non-inferiority. No major PI or INSTI resistance mutations were observed. There were no differences in safety between arms. By week 48, difference (INSTI + DRV/r-SOC) in mean CD4 count change from baseline was -48.3 cells/mm3 (95% CI.: -93.4, -3.2; p = 0.036). Difference (INSTI + DRV/r-SOC) in mean HDL change from baseline was -4.1 mg/dL (95% CI.: -6.7, -1.4; p = 0.003). Weight and Body Mass Index (BMI) increased more in INSTI + DRV/r than SOC [difference: 1.97 kg (95% CI.: 1.1, 2.9; p < 0.001), 0.66 kg/m2 (95% CI.: 0.3, 1.0; p < 0.001)].

INTERPRETATION:

In virologically-suppressed children, switching to INSTI + DRV/r was non-inferior virologically, with similar safety profile, to continuing SOC. Small but significant differences in CD4, HDL-cholesterol, weight and BMI were observed between INSTI + DRV/r vs. SOC although clinical relevance needs further investigation. SMILE data corroborate adult findings and provide evidence for this NRTI-sparing regimen for children and adolescents.

FUNDING:

Fondazione Penta Onlus, Gilead, Janssen, INSERM/ANRS and UK MRC. ViiV-Healthcare provided Dolutegravir.

<b>

OBJECTIVES:

</b>Boosted PIs are commonly prescribed in patients presenting with advanced HIV infection. We assessed the efficacy and tolerability of once-daily ritonavir-boosted atazanavir or darunavir plus two NRTIs in HIV-1-infected ART-naive patients with severe immunosuppression, targeting at least an 85% success rate at week 48.<b>

METHODS:

</b>This 48 week, open-label, non-comparative, randomized, multicentre trial included ART-naive patients with CD4 cell counts <200 cells/mm(3), with plasma HIV-1 RNA >1000 copies/mL and without genotypic mutations conferring resistance to the study drugs. Patients were randomized (1:1) to receive once-daily atazanavir/ritonavir (300/100 mg) or darunavir/ritonavir (800/100 mg) plus tenofovir disoproxil fumarate/emtricitabine or abacavir/lamivudine. The primary endpoint was treatment success, defined as plasma HIV-1 RNA ≤50 copies/mL at week 48 and no permanent PI/ritonavir discontinuation. The study was registered with ClinicalTrials.gov (NCT01928407).<b>

RESULTS:

</b>One hundred and twenty patients were enrolled: 77% were men, 30% were born in Africa and 39% had AIDS. The median baseline CD4 and plasma HIV-RNA values were 69 cells/mm(3) and 5.4 log10 copies/mL. All but four patients received tenofovir disoproxil fumarate/emtricitabine. The week 48 treatment success rate was 66% (95% CI 54%-78%) with atazanavir/ritonavir and 80% (95% CI 68%-89%) with darunavir/ritonavir. The median CD4 cell count increased similarly in the two groups (Δweek 48 to week 0: +194 cells/mm(3)). Adverse events occurred in 23 and 18 patients, respectively.<b>

CONCLUSIONS:

</b>Despite good adherence, neither study regimen reached the predefined objective, suggesting a need for more potent regimens for patients with advanced HIV infection.