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To characterize diet quality across a global cohort of people with HIV (PWH).Cross-sectional analysis.Leveraging REPRIEVE data from baseline across five Global Burden of Disease (GBD) regions, we analyzed participant responses to the Rapid Eating Assessment for Participants questionnaire. An overall diet quality score and scores for specific diet components were generated. Higher scores indicate better diet quality.Among 7736 participants (median age 50 years, 30% women, median BMI 25.8 kg/m 2 ) overall diet quality score (max score 30) was optimal in 13% of participants and good, suboptimal or poor in 45%, 38%, and 4% of participants, respectively; saturated fat score (max score 18) was good, suboptimal, or poor in 38%, 40%, or 7% of participants, respectively. Diet quality scores differed across GBD region with the highest scores reported in the South Asia region [median 23 (21-25)] and lowest in the sub-Saharan Africa region [median 15 (12-18)]; 61% of participants in the South Asia region reported optimal diet quality compared with only 6% in the sub-Saharan Africa region. Higher atherosclerotic cardiovascular risk scores were seen with worsening diet quality.Among PWH eligible for primary CVD prevention, diet quality was suboptimal or poor for almost half of participants, and there were substantial variations in diet quality reported by GBD region.NCT02344290.

Background Paired with other active antiretrovirals (ARVs), fostemsavir (FTR) may offer heavily treatment-experienced (HTE) people with HIV (PWH) options for continuing effective treatment. Durability and effectiveness of FTR-containing regimens in routine clinical care in the United States were assessed. Methods Electronic health record data from the OPERA® cohort were used to identify adults initiating FTR-containing regimens between 2JUL2020 (FDA approval) and 1SEP2021. Eligible PWH were followed from first FTR prescription (baseline) until FTR discontinuation, death, loss to follow up, or study end (28FEB2022). Durability was assessed as frequency of FTR discontinuation. Virologic outcomes assessed at 6 and 12 months (±3 months) included suppression (viral load [VL] < 50 copies/mL), virologic failure (2 consecutive VL ≥200 copies/mL or 1 VL ≥200 copies/mL + FTR discontinuation within 120 days after suppression), and viral blips (1 VL ≥50 copies/mL preceded and followed by VLs < 50 copies/mL). Analyses were stratified by baseline viral load (bVL < 50 copies/mL; bVL ≥50 copies/mL). Results Overall, 86 PWH initiated FTR (bVL < 50: 30; bVL ≥50: 55), with median follow up of 10.8 months (IQR: 6.8, 15.3). Compared to PWH with bVL ≥50, those with bVL < 50 were older and more likely to be white and have lived longer with HIV (Table 1). Over follow up, 20% discontinued FTR (Table 2). Most (82%) FTR discontinuations were switches to alternative regimens; the remaining were ARV interruptions (no ARVs for > 45 days). Among PWH with bVL < 50, most maintained suppression (6 months: 74%; 12 months: 82%; Figure). Among PWH with bVL ≥50 and with follow up VL during the period assessed, 33% were suppressed at 6 months, 36% were suppressed at 12 months, and 48% achieved suppression at any time over the entire follow up (Figure). In either group, ≤5 PWH experienced virologic failure or blip, though the proportion of PWH with multiple follow up VLs was low. Conclusion Despite a heterogenous population and diverse regimens, most HTE PWH remained on FTR at study end. Most PWH with bVL < 50 remained suppressed and half of PWH with bVL ≥50 achieved suppression over the entire study period. Virologic failure and blips were infrequent, although follow up was limited in this early evaluation of real-world FTR use. Disclosures Ricky K. Hsu, MD, Gilead: Honoraria|Merck: Honoraria|ViiV: Advisor/Consultant|ViiV: Grant/Research Support|ViiV: Honoraria Laurence Brunet, PhD, AIDS Healthcare Foundation: Client of my employer|EMD Serono: Client of my employer|Gilead Sciences: Client of my employer|Janssen: Client of my employer|Merck & Co: Client of my employer|TheraTechnologies: Client of my employer|ViiV Healthcare: Client of my employer Jennifer S. Fusco, BS, AIDS Healthcare Foundation: Client of my employer|EMD Serono: Client of my employer|Gilead Sciences: Client of my employer|Janssen: Client of my employer|Merck & Co.: Client of my employer|TheraTechnologies: Client of my employer|ViiV Healthcare: Client of my employer Cassidy Henegar, PhD, MSPH, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: full-time employee Vani Vannappagari, MBBS, MPH, PhD, ViiV Healthcare: I am full time employee of ViiV Healthcare and receive GlaxoSmithKline stock as part of my compensation package|ViiV Healthcare: Stocks/Bonds Andrew Clark, MD, ViiV Healthcare: Employee|ViiV Healthcare: Stocks/Bonds Gerald Pierone, Jr., MD, Gilead: Grant/Research Support|GSK-VIIV: Grant/Research Support Gregory P. Fusco, MD, MPH, AIDS Healthcare Foundation: Client of employer|EMD: Grant/Research Support|Gilead Sciences: Client of employer|Janssen: Client of employer|Merck & Co.: Client of employer|Theratechnologies: Client of employer|ViiV Healthcare: Client of employer.

Background Real-world effectiveness of fixed dose dolutegravir/lamivudine (DTG/3TC) two-drug regimens (2DR) during the first 24 months of availability in the US was compared to common three-drug regimens (3DRs) among suppressed antiretroviral therapy (ART)-experienced people living with HIV (PLWH). Methods Suppressed (viral load [VL] < 200 copies/mL) PLWH initiating DTG/3TC 2DR, bictegravir (BIC)-3DR, or DTG-3DR between 01MAY2019 and 31OCT2020 in the OPERA® Cohort were followed until 30APR2021 (potential for ≥6 months of follow-up). Univariate Poisson regression (incidence rates) and Cox proportional hazards marginal structural models were employed to assess confirmed virologic failure (2 viral loads [VLs] ≥200 copies/mL) or regimen discontinuation. Results Overall, 8037 PLWH were included in the analysis (Table). Virologic failure incidence rates were low, ranging from 0.66 (DTG/3TC) to 1.78 (DTG 3DR) per 100 person-years. Compared to DTG/3TC, only DTG 3DR was associated with an increase in the hazard of virologic failure. Discontinuation incidence rates ranged from 8.30 (BIC 3DR) to 24.9 (DTG 3DR) per 100 person-years. The discontinuation hazard was 69% greater with DTG 3DRs and 49% lower with BIC 3DRs compared to DTG/3TC. Regardless of regimen, most discontinuers were suppressed (VL< 200 copies/mL) at the time of discontinuation (DTG/3TC 2DR: 96%, BIC 3DR: 94%, DTG 3DR: 93%; all p >0.05). Discontinuations following an adverse diagnosis/side effect were uncommon with DTG/3TC 2DR (3%) and DTG 3DR (4%, p=0.5), and higher with BIC 3DR discontinuation (7%, p=0.02). The most common reason for DTG 3DR discontinuations was regimen simplification (21%); no reason was given for >50% of the discontinuations in each group. Conclusion Among ART-experienced, virologically suppressed PLWH, virologic failure was rare after switching to DTG/3TC 2DR, BIC 3DR or DTG 3DR. Most discontinuations were not attributed to the treatment (i.e., loss of suppression, adverse diagnosis, side effects), suggesting other reasons for discontinuation despite high levels of suppression and tolerability. Disclosures Gerald Pierone, Jr., MD, Gilead: Grant/Research Support|GSK-VIIV: Grant/Research Support Jennifer S. Fusco, BS, AIDS Healthcare Foundation: Client of my employer|EMD Serono: Client of my employer|Gilead Sciences: Client of my employer|Janssen: Client of my employer|Merck & Co.: Client of my employer|TheraTechnologies: Client of my employer|ViiV Healthcare: Client of my employer Laurence Brunet, PhD, AIDS Healthcare Foundation: Client of my employer|EMD Serono: Client of my employer|Gilead Sciences: Client of my employer|Janssen: Client of my employer|Merck & Co: Client of my employer|TheraTechnologies: Client of my employer|ViiV Healthcare: Client of my employer Vani Vannappagari, MBBS, MPH, PhD, ViiV Healthcare: I am full time employee of ViiV Healthcare and receive GlaxoSmithKline stock as part of my compensation package|ViiV Healthcare: Stocks/Bonds Supriya Sarkar, PhD, MPH, ViiV Healthcare: Salary|ViiV Healthcare: Stocks/Bonds Cassidy Henegar, PhD, MSPH, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: full-time employee Andrew Zolopa, MD, ViiV Healthcare: full time employee|ViiV Healthcare: Stocks/Bonds Gregory P. Fusco, MD, MPH, AIDS Healthcare Foundation: Client of employer|EMD: Grant/Research Support|Gilead Sciences: Client of employer|Janssen: Client of employer|Merck & Co.: Client of employer|Theratechnologies: Client of employer|ViiV Healthcare: Client of employer.

Background People living with HIV (PLHIV) are at increased risk of atherosclerotic cardiovascular disease (ASCVD) and prone to statin-related adverse events from drug-drug interactions with certain antiretroviral regimens. Objectives This study sought to evaluate the efficacy and safety of evolocumab in dyslipidemic PLHIV. Methods BEIJERINCK is a randomized, double-blind, multinational trial comparing monthly subcutaneous evolocumab 420 mg with placebo in PLHIV with hypercholesterolemia/mixed dyslipidemia taking maximally-tolerated statin therapy. The primary endpoint was the percent change (baseline to week 24) in low-density lipoprotein cholesterol (LDL-C); secondary endpoints included achievement of LDL-C Results A total of 464 patients were analyzed (mean age of 56.4 years, 82.5% male, mean duration with HIV of 17.4 years). ASCVD was documented in 35.6% of patients, and statin intolerance/contraindications to statin use were present in 20.7% of patients. Evolocumab reduced LDL-C by 56.9% (95% CI: 61.6%, 52.3%) from baseline to week 24 versus placebo. An LDL-C level of Conclusions Evolocumab was safe and significantly reduced lipid levels in dyslipidemic PLHIV on maximally-tolerated statin therapy. Evolocumab is an effective therapy for lowering atherogenic lipoproteins in PLHIV with high cardiovascular risk.

People with HIV (PWH) are at an increased risk of atherosclerotic cardiovascular disease. Suboptimal responses to statin therapy in PWH may result from antiretroviral therapies (ARTs). This open-label extension study aimed to evaluate the long-term safety and efficacy of evolocumab up to 52 weeks in PWH.This final analysis of a multinational, placebo-controlled, double-blind, randomized phase 3 trial evaluated the effect of monthly subcutaneous evolocumab 420 mg on low-density lipoprotein cholesterol (LDL-C) during the open-label period (OLP) following 24 weeks of double-blind period in PWH with hypercholesterolemia/mixed dyslipidemia. All participants enrolled had elevated LDL-C or nonhigh-density lipoprotein cholesterol (non-HDL-C) and were on stable maximally tolerated statin and stable ART.Efficacy was assessed by percentage change from baseline in LDL-C, triglycerides, and atherogenic lipoproteins. Treatment-emergent adverse events (TEAEs) were examined.Of the 467 participants randomized in the double-blind period, 451 (96.6%) received at least one dose of evolocumab during the OLP (mean age of 56.4 years, 82.5% male, mean duration with HIV of 17.4 years). By the end of the 52-week OLP, the overall mean (SD) percentage change in LDL-C from baseline was -57.8% (22.8%). Evolocumab also reduced triglycerides, atherogenic lipid parameters (non-HDL-C, apolipoprotein B, total cholesterol, very-low-density lipoprotein cholesterol, and lipoprotein[a]), and increased HDL-C. TEAEs were similar between placebo and evolocumab during the OLP.Long-term administration of evolocumab lowered LDL-C and non-HDL-C, allowing more PWH to achieve recommended lipid goals with no serious adverse events.NCT02833844.http://links.lww.com/QAD/C441.

Background This study compared the effectiveness and durability of DTG/RPV with commonly prescribed 3-drug regimens (3-DR) in people living with HIV (PLWH) in a real-world setting. Methods Antiretroviral therapy (ART)-experienced, virologically suppressed PLWH who initiated DTG/RPV or a 3-DR in 2018 were identified in the OPERA® database and followed through 6/30/2019. Virologic failure (two consecutive viral loads (VL) ≥ 200 copies/mL or single VL ≥ 200 copies/mL with regimen modification/discontinuation) and maintained virologic suppression (last VL test < 50 or < 200 copies/mL) were described. Kaplan–Meier methods were used to estimate time to virologic failure and treatment discontinuation. Risk of virologic failure was adjusted for age, sex, race/ethnicity, risk of infection, region, baseline CD4 cell count, history of substance abuse or syphilis, and mortality risk score at baseline in a Cox model. Results PLWH initiating DTG/RPV were older and more likely to be Hispanic or have comorbidities than 3-DR initiators. DTG/RPV users experienced fewer discontinuations (15%) and were more likely to be suppressed at study end (98%) than 3-DR users (28% and 96%, respectively). Virologic failure was uncommon; rates per 100 person-years did not differ between the DTG/RPV (1.45, 95% CI: 0.69, 3.03) and 3-DR (2.63, 95% CI: 2.21, 3.14) groups. The risk of virologic failure did not differ significantly between the groups in adjusted Cox models (adjusted hazard ratio 1.32, 95% CI: 0.61, 2.89). Conclusions The findings of this real-world OPERA® study suggest that DTG/RPV can be a viable alternative to standard 3-DRs for ART-experienced, virologically suppressed PLWH.

INTRODUCTION Two-drug regimens (2-DR) have the potential to be a viable solution to the challenges of treatment complexity, cost, adverse effects and contraindications. We sought to describe the real-world use and effectiveness of 2-DR among persons living with HIV (PLHIV) in the United States. METHODS We analysed data for 10,190 treatment-experienced patients from the OPERA® Observational Database initiating a new 2-DR or three-drug regimen (3-DR) between 1 January 2010 and 30 June 2016. Multivariate Cox Proportional Hazards models were used to estimate the association among 2-DR or 3-DR initiation and virologic suppression (viral load (VL) 200 copies/mL or 1 VL > 200 copies/mL + discontinuation) or regimen discontinuation. RESULTS Patients initiating a 2-DR (n = 1337, 13%) were older, and more likely to have a lower CD4 count, a history of AIDS and comorbid conditions than patients initiating a 3-DR. There was no difference between groups in time to virologic suppression (aHR: 1.00 (95% CI: 0.88, 1.13)) among viraemic patients (baseline VL ≥ 50 copies/mL, n = 4180), or time to virologic failure (aHR: 1.15 (95% CI: 0.90, 1.48)) among virologically stable patients (baseline VL

Introduction Two‐drug regimens (2‐DR) have the potential to be a viable solution to the challenges of treatment complexity, cost, adverse effects and contraindications. We sought to describe the real‐world use and effectiveness of 2‐DR among persons living with HIV (PLHIV) in the United States. Methods We analysed data for 10,190 treatment‐experienced patients from the OPERA® Observational Database initiating a new 2‐DR or three‐drug regimen (3‐DR) between 1 January 2010 and 30 June 2016. Multivariate Cox Proportional Hazards models were used to estimate the association among 2‐DR or 3‐DR initiation and virologic suppression (viral load (VL) 200 copies/mL or 1 VL > 200 copies/mL + discontinuation) or regimen discontinuation. Results Patients initiating a 2‐DR (n = 1337, 13%) were older, and more likely to have a lower CD4 count, a history of AIDS and comorbid conditions than patients initiating a 3‐DR. There was no difference between groups in time to virologic suppression (aHR: 1.00 (95% CI: 0.88, 1.13)) among viraemic patients (baseline VL ≥ 50 copies/mL, n = 4180), or time to virologic failure (aHR: 1.15 (95% CI: 0.90, 1.48)) among virologically stable patients (baseline VL

Background and Objectives The standard of care for HIV treatment is a three-drug regimen consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) and either a non-nucleoside reverse transcriptase inhibitor, a protease inhibitor (PI) or an integrase strand transfer inhibitor. Darunavir boosted with ritonavir (DRV/r) is the only preferred PI in the US Department of Health and Human Services (DHHS) HIV treatment guidelines for antiretroviral-naïve patients, recommended in combination with tenofovir/emtricitabine for antiretroviral-naïve patients. For treatment-experienced and certain antiretroviral-naïve patients, abacavir and lamivudine (ABC/3TC) in combination with DRV/r is considered an effective and tolerable alternative, despite limited research on the effectiveness of this particular combination. This study evaluated virologic outcomes in treatment-experienced patients taking ABC/3TC + DRV/r compared to treatment-experienced patients taking ABC/3TC with any other PI. Methods Treatment-experienced HIV-infected patients initiating their first regimen containing ABC/3TC in combination with any PI in the year 2005 or later were selected from the Observational Pharmaco-Epidemiology Research and Analysis (OPERA®) cohort, a prospective observational cohort reflecting routine medical care. Viral load measurements taken during follow-up were compared between patients taking ABC/3TC + DRV/r and ABC/3TC with a PI other than DRV/r. Logistic regression models were fit to assess the association between regimen exposure and viral load suppression. Results A total of 151 patients initiating ABC/3TC + DRV/r and 525 patients initiating ABC/3TC + a non-darunavir PI were included. Patients in both treatment groups had comparable clinical indicators (viral load, CD4) at baseline. A regimen of ABC/3TC + DRV/r was more likely to be prescribed in the later years of the study period, leading to a shorter median follow-up in the DRV/r treatment group (as-treated analysis: 14 vs. 17 months, p = 0.04; intent-to-treat analysis: 33 vs. 68 months, p

Background In 2017, the first complete antiretroviral regimen (ART) containing only two drugs, dolutegravir/rilpivirine (DTG/RPV), was approved for treatment of HIV-1 in virologically suppressed ( Methods HIV-1+ individuals initiating DTG/RPV from January 1, 2018 to December 31, 2018 were identified in the OPERA Database. Outcomes were evaluated among the virologically suppressed subgroup who initiated in the first 6 months. Discontinuation (d/c) was defined as cessation of DTG/RPV. Virologic failure (VF) was defined as either 2 consecutive HIV viral loads (VL) ≥ 200 copies/mL OR 1 VL ≥200 copies/mL + d/c. Population was observed from DTG/RPV start (index) until the first of: (a) d/c, (b) death, or (c) study end (December 31, 2018). Demographic and clinical characteristics were described at index. Kaplan–Meier methods were used to describe d/c and VF. Results A total of 880 patients were prescribed DTG/RPV in the first 12 months; demographic and clinical characteristics are described in Figures 1 and 2. Most (76%) DTG/RPV users were virologically suppressed at initiation (n = 671). Among the 197 (22%) ART experienced, viremic initiators, a third had a baseline VL ≥ 50 but Conclusion While DTG/RPV initiators were primarily ART-experienced, virologically suppressed individuals older than 50 years of age challenged by significant comorbid conditions, the frequency of d/c or VF in the first 12 months was low. Disclosures All authors: No reported disclosures.

Background Progressive multifocal leukoencephalopathy (PML) is a deadly demyelinating disease of the brain, caused by reactivation of the polyomavirus JC (JCV). PML has classically been described in individuals with profound cellular immunosuppression such as patients with AIDS, haematological malignancies, organ transplant recipients or those treated with immunosuppressive or immunomodulatory medications for autoimmune diseases. Methods and case reports The authors describe five HIV seronegative patients with minimal or occult immunosuppression who developed PML including two patients with alcoholic cirrhosis, one with untreated dermatomyositis and two with idiopathic CD4 + T cell lymphocytopenia. The authors performed a review of the literature to find similar cases. Results The authors found an additional 33 cases in the literature. Of a total of 38 cases, seven (18.4%) had hepatic cirrhosis, five (13.2%) had renal failure, including one with concomitant hepatic cirrhosis, two (5.2%) were pregnant women, two (5.2%) had concomitant dementia, one (2.6%) had dermatomyositis, and 22 (57.9%) had no specific underlying diagnosis. Among these 22, five (22.7%) had low CD4 + T cell counts (0.080–0.294×10 9 /l) and were diagnosed as having idiopathic CD4 + lymphocytopenia, and one had a borderline CD4 + T cell count of 0.308×10 9 /l. The outcome was fatal in 27/38 (71.1%) cases within 1.5–120 months (median 8 months) from onset of symptoms, and 3/4 cases who harboured JCV-specific T cells in their peripheral blood had inactive disease with stable neurological deficits after 6–26 months of follow-up. Discussion These results indicate that PML can occur in patients with minimal or occult immunosuppression, and one can revisit the generally accepted notion that profound cellular immunosuppression is a prerequisite for the development of PML.

Background Given the limited treatment options for patients with high-level resistance, antiretroviral (ARV) regimens based on concomitant use of 2 ritonavir (RTV)-boosted protease inhibitors (PIs) were considered a therapeutic option. Methods Boehringer Ingelheim (BI) study 1182.51 examined the pharmacokinetic profile, safety, and efficacy of RTV-boosted tipranavir (TPV/r), alone and in combination with comparator PIs (CPIs) in 315 triple-class-experienced, HIV-infected patients. Results Two weeks after single PI therapy, the addition of TPV/r reduced plasma trough levels 52%, 80%, and 56% for lopinavir (LPV), saquinavir (SQV), and amprenavir (APV) recipients, respectively. After 2 weeks, a TPV/r-only regimen reduced HIV viral load (VL) by a median of 1.06 log(10) copies/mL. VL reductions at 2 weeks between single-boosted CPIs were difficult to compare, because the numbers of patients maintaining their previous failing PI after randomization were different. At week 4, patients initiating treatment with TPV-containing regimens sustained VL reduction (median decrease of 1.27 log(10) copies/mL). Patients adding TPV to regimens at week 2 achieved median reductions from a baseline of 1.19 log(10), 0.96 log(10), and 1.12 log(10) copies/mL at week 4 in dual-boosted LPV, SQV, and APV groups, respectively. At 24 weeks, VL reductions (median: -0.24 to -0.47 log(10) copies/mL) were comparable between treatment groups. Conclusions The efficacy of a dual PI regimen depended on the presence of TPV, with additional recycled CPIs having limited activity, even in drug-resistant patient populations with plasma trough concentrations regarded as likely to be adequate in this study. No clear guidelines exist about ARV plasma trough concentrations in treatment-experienced patients, however.

Background: Obstructive sleep apnea (OSA) is a common disorder that is linked to daytime fatigue and increased risk of cardiovascular disease. The general population prevalence of OSA is estimated to be 2-9%. The prevalence of OSA in people with HIV infection is unknown, although many patients with HIV report daytime fatigue. The diagnosis of OSA is typically established during an overnight study in a sleep laboratory. Sleep surveys designed to select have been previously validated for selecting patients for definitive study. Nocturnal oxygen desaturation index (ODI) measurement has also been used to screen for reliably predicting over 85% of moderate to severe cases when the ODI >10. Methodology: Patients with HIV infection presenting for routine medical care were invited to participate in this prospective OSA screening trial. Informed consent was obtained; subjects completed the Four-Variable Screening Tool, the STOP-BANG questionnaire, Epworth Sleepiness Scale, and were provided a fingertip oximeter for overnight use at home. Overnight oxygen saturation data was analyzed and correlated to corresponding sleep surveys. All subjects with ODI >10 were referred for a formal sleep study. Results: 156 subjects completed the study and 66 (42.3%) demonstrated an ODI >10. Of the 66, 21 pursued formal sleep studies. 14 of the 21 tested positive for OSA. The Four-Variable Screening Tool had the highest positive predictive value of 59.5%, and the STOP-BANG questionnaire had the highest negative predictive value of 76.9%. Conclusions: HIV-infected patients in our clinic demonstrated a high prevalence of nocturnal oxygen desaturation suggesting a high prevalence of OSA. Three commonly used screening tools did not reliably predict nocturnal desaturation in our population. The high prevalence of nocturnal oxygen desaturation and in HIV patients indicates the need for additional HIV-related OSA research.

This study evaluated the safety and efficacy of switching HIV-infected patients with stable viral suppression on nonnucleoside reverse transcriptase inhibitor/nucleoside reverse transcriptase inhibitor (NNRTI/NRTI) therapy to lopinavir/ritonavir (LPV/r) monotherapy.Eligible patients discontinued NNRTI and started LPV/r. Two weeks later NRTIs were stopped and LPV/r monotherapy was continued. Patients were seen every 4 weeks throughout the 48-week study.Twelve of 18 (66%) participants met the primary endpoint with HIV RNA75 copies/mL at week 48. Thirteen (72%) participants completed 48 weeks of LPV/r monotherapy, and 12 of 13 (92%) participants on treatment at week 48 had HIV RNA75 copies/mL. Ten (55%) of 18 patients maintained HIV RNA75 copies/mL at all time points. Two patients were withdrawn with virologic failure but demonstrated no evidence of virologic resistance. Three (17%) patients withdrew due to diarrhea, 2 with hyperglycemia at baseline developed diabetes mellitus, 7 (54%) required addition of or increase in lipid-lowering agents, but none had grade 3 or 4 hyperlipidemia.Results from this pilot study suggest that LPV/r monotherapy may be an option for management of HIV infection. Larger, randomized trials are warranted to evaluate the safety, efficacy, and patient population who might benefit from LPV/r monotherapy.

Objective The objective of this study was to determine whether a triple therapy regimen incorporating twice-daily saquinavir is as effective as a three-times daily regimen. Methods This was an open-label, Phase III, multicentre, 48-week study involving 837 HIV-1-infected patients randomised to one of the following: saquinavir soft gel capsule (SGC) 1200 mg three-times daily, plus two nucleoside reverse transcriptase inhibitors (NRTIs) (arm A); saquinavir SGC 1600 mg twice-daily, plus two NRTIs (arm B); saquinavir SGC 1200 mg twice-daily and nelfinavir 1250 mg twice-daily, plus a single NRTI (arm C). The primary outcome measure was the virological response in arm A versus B and in arm A versus C with respect to the percentage of patients whose plasma HIV-1 RNA levels fell below the level of quantification for the Amplicor assay (Results At 48 weeks, the percentage of patients with plasma HIV-1 RNA levels Conclusions A twice-daily triple therapy regimen incorporating saquinavir SGC plus two NRTIs was of equivalent efficacy to the three-times daily regimen studied. All regimens were generally well tolerated.

Objectives To evaluate the efficacy, safety, and tolerability of repeated NGX-4010 treatments in the open-label extension phase of a 52-week study in patients with neuropathic pain due to HIV-associated distal sensory polyneuropathy (HIV-DSP). Methods Patients completing the 12-week, randomized, double-blind phase of the study could enter a 40-week, open-label phase, and receive up to 3, 60-minute NGX-4010 treatments. Patients recorded their "average pain for the past 24 hours" daily using the Numeric Pain Rating Scale (NPRS). Efficacy assessment included the percentage NPRS score reduction from baseline to weeks 2 to 12 after the final treatment, and Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) questionnaires at study termination. Results Of 307 patients randomized, 272 entered the open-label phase; 81, 90, 55, and 46 received 0, 1, 2, and 3 retreatments, respectively. The mean percentage decrease in NPRS score from baseline to weeks 2 to 12 after the final treatment was similar in patients receiving single or multiple NGX-4010 treatments (-25.8%, -27.1%, -24.6%, and -22.7% for 1, 2, 3, and 4 NGX-4010 treatments, respectively). PGIC and CGIC results demonstrated a benefit of NGX-4010 treatment through to the end of the study regardless of the number of treatments received. Transient local application site reactions were the most frequently reported adverse events, and were mainly mild to moderate, nonserious, and did not increase with repeated treatment. Discussion Repeated NGX-4010 treatments were generally well tolerated and resulted in consistent reductions in HIV-DSP-associated pain and improvement in patient-reported outcomes.

BACKGROUND Studies of injectable poly-L-lactic acid (PLLA) in human immunodeficiency virus (HIV)-associated facial lipoatrophy have predominantly included male Caucasians. OBJECTIVE To report cumulative year 2 interim study results examining the safety and efficacy of injectable PLLA in subjects with HIV categorized according to Fitzpatrick skin type and sex. MATERIALS AND METHODS This is an ongoing open-label, multicenter, 5-year study of 290 treated subjects. After correction with injectable PLLA, subjects are being followed annually. Primary end points include incidence and severity of treatment-emergent adverse events (TEAEs). Secondary end points include mean change from baseline of James scale severity grade and treatment satisfaction. RESULTS At 2 years, TEAE incidences were: potentially related to study product (n = 53,18.3%) or injection procedure (n = 71, 24.5%), injection-site nodules (n = 24, 8.3%) and papules (n = 25, 8.6%). No hypertrophic scars, keloids, or product-related serious TEAEs were reported. Mean improvement in James scale grade for all groups was 1.4 (p < .001), and 89.4% of subjects and 95.5% of physicians rated treatment satisfaction as very good or excellent. CONCLUSION At 2 years, injectable PLLA is a safe and effective long-term treatment for HIV-associated facial lipoatrophy regardless of Fitzpatrick skin type; confirmation of these results will be needed at the completion of this 5-year study.

Previous studies of lopinavir/ritonavir (LPV/r) monotherapy have shown that over 70% of patients achieved HIV RNA levels

BACKGROUND Agents for the treatment of HIV-1-infected patients with resistance to current antiretroviral (ART) drugs are needed. METHODS TMC114-C202 was a randomized, partially blinded, dose-finding study in treatment-experienced HIV-1-infected patients with one or more primary protease inhibitor (PI) mutations and HIV-1 RNA > 1000 copies/ml. Patients were randomized to receive one of four TMC114 doses given with ritonavir (TMC114/r) or investigator-selected control PI drug(s) (CPI); all received an optimized background regimen. The primary intent-to-treat analysis compared the proportion of patients achieving a >or= 1 log10 copies/ml HIV-1 RNA reduction at week 24 between the treatment arms using the time-to-loss of virological response algorithm. RESULTS For 278 patients at baseline, mean HIV-1 RNA was 4.7 log10 copies/ml, median CD4 cell count was 106 cells/mul; HIV-1 isolates had a median of three primary PI mutations and a median fold change in lopinavir susceptibility of 80. Discontinuation rates were 23% for TMC114/r versus 64% for CPI. More patients in each TMC114/r dose group achieved >or= 1.0 log10 copies/ml reduction in HIV-1 RNA than in the CPI group (45-62% versus 14%; P

Clinicians are increasingly challenged by presentation of morphologic and metabolic complications in HIV-infected patients. These complications are associated with HIV infection and/or combination antiretroviral therapy. This Consensus Statement is intended to offer guidance to clinicians actively involved in HIV/AIDS care.Seven clinicians with expertise in HIV medicine were invited by the International Association of Physicians in AIDS Care (IAPAC) to serve on an ad hoc Advisory Committee.IAPAC convened the Advisory Committee to develop a draft Consensus Statement. Each clinician was tasked with drafting a specific section of the Consensus Statement corresponding with his or her expertise around a morphologic and/or metabolic complication. Scientific and clinical research, and other data in published literature and abstracts from scientific conferences were considered by strength of evidence. This document represents the consensus agreement of the Advisory Committee.

The objective of this study was to determine whether a triple therapy regimen incorporating twice-daily saquinavir is as effective as a three-times daily regimen.This was an open-label, Phase III, multicentre, 48-week study involving 837 HIV-1-infected patients randomised to one of the following: saquinavir soft gel capsule (SGC) 1200 mg three-times daily, plus two nucleoside reverse transcriptase inhibitors (NRTIs) (arm A); saquinavir SGC 1,600 mg twice-daily, plus two NRTIs (arm B); saquinavir SGC 1,200 mg twice-daily and nelfinavir 1,250 mg twice-daily, plus a single NRTI (arm C). The primary outcome measure was the virological response in arm A versus B and in arm A versus C with respect to the percentage of patients whose plasma HIV-1 RNA levels fell below the level of quantification for the Amplicor assay (400 copies/ml) at weeks 24 and 48.At 48 weeks, the percentage of patients with plasma HIV-1 RNA levels400 copies/ml was 47.1% (arm A), 45.3% (arm B) and 42.7% (arm C) in the intention-to-treat analysis. The treatment difference between arm B-arm A was -1.8% (95% confidence intervals -10.1, 6.5) and for arm C-arm A was -4.5% (95% confidence intervals -12.7, 3.7) in the intention-to-treat analysis. These differences fell within the maximum allowable difference (+/- 12%) for arm B compared with arm A. At week 24, the percentage of patients with HIV-1 RNA levels400 copies/ml was 59.6% (arm A), 57.6% (arm B) and 51.3% (arm C).A twice-daily triple therapy regimen incorporating saquinavir SGC plus two NRTIs was of equivalent efficacy to the three-times daily regimen studied. All regimens were generally well tolerated.

s of the 46th Annual ICAAC; September 27–30, 2006; San Francisco, CA. Poster A-0374. 8. Kumar PN CD, Steigbigel RT, et al. Efficacy of raltegravir, an integrase inhibitor, in combination with regimens containing enfuvitide, darunavir, or tipranavir in patients with tripleclass resistant virus: combined results from BENCHMRK-1 and BENCHMRK-2. In: Programs and abstracts of the 11th European AIDS Conference; October 24–27, 2007; Madrid, Spain, Poster P7.2/06. 1 10 100 1000 10000 100000 1000000 0 25 50 75 100 125 150 175 200 Follow-Up Period (weeks) H IV R N A ( co p ie s/ m L ) an d C D 4+ L ym p h o cy te (c el ls /μ L ) 0 20 40 60 80 100 120 140 160 180

Background: Resistance to antiretroviral agents remains a leading cause of treatment failure for patients infected with HIV-1. Objective: To describe the efficacy and safety of tenofovir disoproxil fumarate (tenofovir DF) compared with placebo in patients with detectable viral replication despite current antiretroviral therapy. Design: Randomized, double-blind, placebo-controlled study through 24 weeks. After 24 weeks, all patients received open-label tenofovir DF for the remainder of the 48-week study. Setting: 75 North American, European, and Australian HIV clinics. Patients: 552 HIV-1-infected adults who were receiving antiretroviral therapy and had stable HIV-1 RNA levels ranging from 400 to 10 000 copies/mL. Measurements: Change in HIV-1 RNA level (time-weighted average from baseline through week 24); proportion of patients with grade 3 or 4 laboratory abnormalities and adverse events; and genotypic HIV-1 resistance testing in a separate substudy at baseline, week 24, and week 48. Results: A statistically significant decrease in HIV-1 RNA level through week 24 (the primary end point) was observed in the tenofovir DF group versus the placebo group (-0.61 log 10 copies/mL vs. -0.03 log 10 copies/mL, respectively [P < 0.001]; difference, -0.58 log 10 copies/mL [95% Cl, -0.68 to -0.49 log 10 copies/mL]). In a virologic substudy, 94% of 253 patients had plasma isolates expressing reverse transcriptase mutations associated with nucleoside resistance mutations at baseline. Through week 24, the incidence of clinical adverse events was similar between patients receiving placebo and those receiving tenofovir DF (14% vs. 13%). No evidence of tenofovir DF-related toxicity was seen through week 48. Conclusion: In treatment-experienced patients with suboptimal viral suppression, tenofovir DF significantly reduced HIV-1 RNA level and had a safety profile similar to that of placebo.