Rates Of Virologic Suppression Research Articles

Baseline Antiretroviral Resistance Mutations and Treatment-Emergent Resistance in HIV-1 RNA-Suppressed Patients Switching to EVG/COBI/FTC/TDF or Continuing on Their PI-, NNRTI-, or RAL-Based Regimen

Stably suppressed HIV-1-infected patients that switched to elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) from regimens containing FTC/TDF plus a ritonavir-boosted protease inhibitor (PI + RTV), nonnucleoside reverse transcriptase inhibitor (NNRTI), or raltegravir in phase 3 studies STRATEGY-PI, STRATEGY-NNRTI, and GS-US-236-0123 maintained high rates of virologic suppression through 48 weeks. In this article, resistance analyses for these studies are described. HIV-1 historical genotypes obtained before therapy initiation were analyzed for preexisting/transmitted resistance (-R) in protease and reverse transcriptase (RT) and subtype. Patients with resistance to FTC/TDF were excluded. Viral isolates with HIV-1 RNA ≥400 copies per milliliter at confirmed virologic failure, discontinuation, or week 48 were analyzed for protease, RT, and integrase genotype and phenotype. Historical genotypes from 626/628 subjects that switched to EVG/COBI/FTC/TDF indicated 25% had ≥1 primary resistance mutation in protease and/or RT. NNRTI-R was identified in 15%, NRTI-R in 8.3%, and PI-R in 3.7% of subjects. Week 48 virologic success rates (HIV-1 RNA <50 copies per milliliter) were 94% for all patients treated with EVG/COBI/FTC/TDF, 94% with preexisting resistance, 93% with subtype B, and 96% with non-B subtypes. Altogether, 2 subjects qualified for postbaseline resistance analyses. Neither had emergent resistance, and both resuppressed to HIV-1 RNA <50 copies per milliliter with no change in therapy. Switching antiretroviral regimens to EVG/COBI/FTC/TDF in HIV-1 RNA-suppressed FTC/TDF-sensitive patients resulted in maintained virologic suppression through 48 weeks. Similar virologic success rates were achieved irrespective of the presence of preexisting resistance mutations or subtype. The lack of emergent resistance through 48 weeks supports utility of EVG/COBI/FTC/TDF for treatment-experienced patients seeking regimen modification or simplification.

Risk Factors and Mortality Associated With Resistance to First-Line Antiretroviral Therapy

Understanding the factors associated with HIV drug resistance development and subsequent mortality is important to improve clinical patient management. Analysis of individual electronic health records from 4 HIV programs in Malawi, Kenya, Uganda, and Cambodia, linked to data from 5 cross-sectional virological studies conducted among patients receiving first-line antiretroviral therapy (ART) for ≥6 months. Adjusted logistic and Cox-regression models were used to identify risk factors for drug resistance and subsequent mortality. A total of 2257 patients (62% women) were included. At ART initiation, median CD4 cell count was 100 cells per microliter (interquartile range, 40-165). A median of 25.1 months after therapy start, 18% of patients had ≥400 and 12.4% ≥1000 HIV RNA copies per milliliter. Of 180 patients with drug resistance data, 83.9% had major resistance(s) to nucleoside or nonnucleoside reverse transcriptase inhibitors, and 74.4% dual resistance. Resistance to nevirapine, lamivudine, and efavirenz was common, and 6% had etravirine cross-resistance. Risk factors for resistance were young age (<35 years), low CD4 cell count (<200 cells/μL), and poor treatment adherence. During 4978 person-years of follow-up after virological testing (median = 31.8 months), 57 deaths occurred [rate = 1.14/100 person-years; 95% confidence interval (CI): 0.88 to 1.48]. Mortality was higher in patients with resistance (hazard ratio = 2.08; 95% CI: 1.07 to 4.07 vs. <400 copies/mL), and older age (hazard ratio = 2.41; 95% CI: 1.24 to 4.71 for ≥43 vs. ≤34 years), and lower in those receiving ART for >30 months. Our findings underline the importance of optimal treatment adherence and adequate virological response monitoring and emphasize the need for resistance surveillance initiatives even in HIV programs achieving high virological suppression rates.

Rates and Correlates of Antiretroviral Therapy Use and Virologic Suppression Among Perinatally and Behaviorally HIV-Infected Youth Linked to Care in the United States

To measure rates of antiretroviral therapy (ART) use and virologic suppression among perinatally HIV-infected youth (PIY) and behaviorally HIV-infected youth (BIY) linked to care in the United States and examine the effects of demographic, biomedical, and psychosocial factors on those rates. Between 2009 and 2012, 649 PIY and 1547 BIY in 20 Adolescent Medicine Trials Network for HIV/AIDS Interventions sites completed cross-sectional surveys through audio computer-assisted self-interviews. Viral load data were collected from chart abstraction or blood draw. Overall 82.4% of PIY and 49.1% of BIY reported current ART use. Only 37.0% of PIY and 27.1% of BIY were virologically suppressed. Virologic suppression rates did not vary as a function of time since HIV diagnosis in either group. Consistent HIV care and no current substance abuse were significant correlates of ART use among PIY. These variables and non-African American race were some factors associated with virologic suppression for PIY [odds ratios (ORs) P < 0.05]. Among BIY, older age, heterosexuals, employment, and education were significantly related to ART use (ORs: P < 0.05); suppression was related to ART use ≥6 months, ≥90% ART adherence, and consistent HIV care (ORs: P < 0.05). Nearly 75% (n = 498) of nonsuppressed youth reported unprotected sex in the past 3 months. There are continued challenges with successfully treating youth even once diagnosed and linked to HIV care. Strategies targeting barriers to ART access, use, and virologic suppression are needed to optimize the impact of the "Treatment as Prevention" paradigm among PIY and BIY.

Analysis on HIV suppression effect after initiating antiretroviral treatment and related factors among AIDS patients in Henan province during 2008 and 2013

To compare the HIV suppression rate after initiating antiretroviral treatment(ART) among AIDS patients at different immunological levels and to analyze the related factors. Data on AIDS patients initially starting antiretroviral therapy during 2008 and 2013 were collected from Chinese HIV/AIDS integrated control system. All the participants were divided into early treatment group(baseline CD4(+)T cell counts between 351/µl and 500/µl) and conventional treatment group(baseline CD4(+)T cell counts ≤ 350/µl). The rates of comprehensive virologic suppression at different time nodes after the initiation of ART were analyzed accordingly. Unconditional logistic regression model was adopted to examine the factors associated with the failure of viral suppression after 6 months after initiation of ART. A total of 16 103 cases were selected, among which, 1 581 cases were early treatment group, and 14 522 cases were conventional treatment group. A total of 9 428 cases were males, 6 675 cases were females, and the sex ratio was 1.41: 1. The age was 47.2 ± 11.7, and 71.55% (11 522/16 103) of cases were married or cohabiting, 57.22% (9 214/16 103) were transmitted by blood. 81.26% (13 086/16 103) were cures in the township or village treatment institution, and 77.17% (12 426/16 103) received the ART regimen as Stavudine(D4T) or Zidovudine(AZT)+Lamivudine(3TC)+Nevirapine(NVP) or Efevirenz(EFV). After 0.5, 1, 2, 3, 4, 5 and 6 years after the initiation of ART, the rates of virologic suppression in the conventional treatment cohort were 72.6% (3 008/4 144), 73.9% (4 758/6 443), 74.1% (3 641/4 915), 74.9% (2 819/3 766), 76.1% (1 729/2 272) and 78.2% (492/629), respectively. While the rates of viral suppression in the early treatment cohort at the same time nodes were 65.5% (315/481), 65.4% (448/685), 68.8% (223/324), 66.0% (155/235), 71.4% (110/154) and 61% (30/49), respectively, and the differences between the two groups were significant (P < 0.05) except at the fourth year. Non-conditional logistic regression analysis showed that in the conventional treatment group, factors associated with low HIV suppression rate were male (OR = 1.23, 95%CI:1.07-1.42) , longer time interval from confirmed HIV infection to received ART (OR = 1.26, 95%CI:1.16-1.36) , using D4T/AZT+ DDI +NVP/EFV as initial treatment regimen (OR = 3.00, 95%CI:2.26-3.98) and nearly missing doses for 7 days at treatment of six months (OR = 1.97, 95%CI:1.22-3.18) and factors associated with high HIV suppression rate were infected through homosexual transmission route (OR = 0.57, 95%CI:0.35-0.90) and treated in the county level medical institution or above (OR = 0.61, 95%CI:0.50-0.75) . Among early treatment group, cases who received treatment at county level medical institution or above had high HIV suppression rate (OR = 0.43, 95%CI:0.23-0.80) and objects with longer time interval from confirmed HIV infection to receive ART had low HIV suppression rate (OR = 1.43, 95%CI:1.09-1.88). The viral suppression efficacy among AIDS patients with different baseline immunologic levels after treatment was similarly satisfactory. AIDS cases who received ART at county level medical institution or above had better viral suppression effect and patients with longer time interval from confirmation to treatment had poor HIV suppression effect.

Use of efavirenz or atazanavir/ritonavir is associated with better clinical outcomes of HAART compared to other protease inhibitors: routine evidence from the Italian MASTER Cohort

Randomized trials and observational cohorts reported higher rates of virological suppression after highly active antiretroviral therapy (HAART) including efavirenz (EFV), compared with boosted protease inhibitors (PIs). Correlations with immunological and clinical outcomes are unclear. Patients of the Italian MASTER cohort who started HAART from 2000 to 2010 were selected. Outstanding outcome (composite outcome for success (COS)) was introduced. We evaluated predictors of COS (no AIDS plus CD4+ count >500/mm3plus HIV-RNA <500 copies/mL) and of eight single outcomes either at month 6 or at year 3. Multivariable logistic regression was conducted. There were 6259 patients selected. Patients on EFV (43%) were younger, had greater CD4+ count, presented with AIDS less frequently, and more were Italians. At year 3, 90% of patients had HIV RNA <500 copies/mL, but only 41.4% were prescribed EFV, vs. 34.1% prescribed boosted PIs achieved COS (p <0.0001). At multivariable analysis, patients on lopinavir/ritonavir had an odds ratio of 0.70 for COS at year 3 (p <0.0001). Foreign origin and positive hepatitis C virus-Ab were independently associated with worse outcome (OR 0.54, p <0.0001 and OR 0.70, p 0.01, respectively). Patients on boosted PIs developed AIDS more frequently either at month 6 (13.8% vs. 7.6%, p <0.0001) or at year 3 (17.1% vs. 13.8%, p <0.0001). At year 3, deaths of patients starting EFV were 3%, vs. 5% on boosted PIs (p 0.008). In this study, naïve patients on EFV performed better than those on boosted PIs after adjustment for imbalances at baseline. Even when virological control is achieved, COS is relatively rare. Hepatitis C virus-positive patients and those of foreign origin are at risk of not obtaining COS.

Socio-economic factors and virological suppression among people diagnosed with HIV in the United Kingdom: results from the ASTRA study.

IntroductionIn the United Kingdom, rates of virological suppression on antiretroviral therapy (ART) are very high, but there remain a small but significant number of people on ART with detectable viraemia. The impact of socio-economic factors on virological suppression has been little studied.Materials and MethodsWe used data from ASTRA, a cross-sectional, questionnaire study of >3000 individuals from 8 clinics in the United Kingdom in 2011–2012, linked to clinical records to address this question. Included participants had received ART for >6 months with a recorded current viral load (VL) (latest at the time of questionnaire). Participants provided data on demographic factors: gender, sexual orientation, ethnicity and age; and socio-economic factors: UK birth/English reading ability, employment, housing, education and financial hardship. To assess non-adherence, participants were asked if in the past 3 months, they had missed ART for ≥2 days at a time. Virological suppression was defined as VL≤50 cps/mL. For each socio-economic factor, we calculated prevalence ratios using modified Poisson regression, first adjusting for demographic factors, then also for non-adherence.ResultsA total of 2445 people fulfilled the inclusion criteria (80% male, 69% MSM, median age: 46 years, median CD4 count: 556 cells/mm3); 10% (234/2445) had VL>50 cps/mL. After adjusting for demographic factors, non-fluent English, not being employed, not home owning, education below university level and increasing financial hardship were each associated with higher prevalence of VL>50 cps/mL. Additional adjustment for non-adherence largely attenuated each association, but did not fully explain them (see Table 1). After adjustment for non-adherence and demographic factors, younger age was also associated with VL>50 cps/mL: for each additional 10 years an individual was 0.80 (95% CI 0.70–0.92) times as likely to have VL>50 cps/mL (p=0.0019). Adjusted prevalence ratios for VL>50cps/mL were 0.91 (0.62–1.34) for women and 1.25 (0.85–1.84) for non-MSM men versus MSM, and 1.29 (0.92–1.80) for white versus non-white people. ConclusionsAmong people on ART in the United Kingdom, the proportion with detectable VL is low. Poorer socio-economic status is associated with increased probability of virological non-suppression. It is likely that much of this association is mediated through difficulties in taking ART. Emphasis should be put on aiding the adherence of people in these higher risk groups.

G-113 Perinatally HIV infected adolescents and early transition to adult care

Background: Adolescents with chronic diseases require youth directed services. In Jamaica, children are transferred at age 12 years to adult care in the public hospitals. We compare the outcomes of perinatally HIV infected adolescents (PHIVA) who were transferred to adult care with those in pediatric care. Methods: Adolescents aged 10–19 years from both adult and pediatric clinics were enrolled in an adolescent clinic established at Cornwall Regional Hospital in 2014. Demographic, clinical, lab and adherence (clinic visits, pharmacy refill, self reported medication) were reviewed from surveillance data, charts and adherence counselor reports. PHIVA in adult and pediatric care were compared and factors associated with sustained viral suppression (<400 copies/ml) were reviewed using student's t test and chi square analysis. Results: Among 57 PHIVA, 22 (38%) were transferred to adult care at a median age of 13 years after a median of 5 years in pediatric care. At the time of transfer to adult care 10 (45%) were on first line treatment, the median CD4 was 486/mm3 (range 23–2342) and 7 (32%) had viral suppression. Five children died (4 in adult cares) and 2 defaulted (pediatric care). Mean ages were 16 years and 12 years in adult and pediatric clinic cohort respectively. Full disclosure was made to 90% of adolescents in adult care and 28% in pediatric care (P < 0001 ). Viral suppression was noted in 36% of children in adult care compared with 64% in pediatric care (P < 0.05).Virologic suppression rates were 31/100 person years and 37/100 person years in adult and pediatric clinics respectively. An undetectable status was associated with vigilant caregiver support (P = 0.002). The children who died all had poor caregiver support (P < 0.001). Conclusions: Premature transition to adult care may result in a reduction of viral suppression rates without adequate youth directed services. Caregiver vigilance must be maintained and youth friendly services be advocated for in resource limited settings to ensure survival of this aging cohort.

High rates of viral suppression in a cohort of HIV-positive adults receiving ART in Ethiopian health centers irrespective of concomitant tuberculosis.

IntroductionAntiretroviral therapy (ART) initiation during treatment for tuberculosis (TB) improves survival in HIV/TB co-infected patients. Data on ART outcome for HIV/TB co-infected patients managed in primary health care in low-income regions is limited. We compared virological suppression rates, mortality and retention in care in HIV-positive adults receiving care in five Ethiopian health centres with regard to TB co-infection.Materials and MethodsHIV-positive ART-naïve adults eligible for ART initiation were prospectively recruited from October 2011 until March 2013. At inclusion, all patients submitted sputum for microbiological TB testing (smear microscopy, liquid culture and PCR). Virological suppression rates after six months of ART (VS; viral load <40 and <400 copies/mL) with regard to TB status was the primary outcome. The impact of HIV/TB co-infection on VS rates was determined by multivariate regression analysis. Mortality and retention in care were analyzed by proportional hazard models.ResultsAmong 812 participants (TB 158; non-TB 654), 678 started ART during the follow-up period (TB 135; non-TB 543). Median CD4 cell counts at ART initiation were 161 cells/µL (interquartile range [IQR], 98–243) and 184 (IQR, 118–256) for TB and non-TB patients, respectively (p=0.05). No difference in retention in care between TB and non-TB patients was observed during follow-up; 25 (3.7%) patients died and 17 (2.5%) were lost to follow-up (p=0.30 and p=0.83, respectively). Overall rates of VS at six months were 72.1% (<40 copies/mL) and 88.7% (<400 copies/mL), with similar results for subjects with and without TB co-infection (<40 copies/mL: 65/92 (70.7%) vs. 304/420 (72.4%), p=0.74; <400 copies/mL: 77/92 (83.7%) vs. 377/420 (89.8%), p=0.10, respectively). CD4 cell count increase during treatment was 87 (IQR, 26–178) and 103 cells/µL (IQR, 38–173) for TB and non-TB patients, respectively, with no significant difference between the two groups (p=0.49).ConclusionsHigh rates of VS were achieved in adults receiving ART at Ethiopian health centres managed by non-physician clinicians, with no significant difference with regard to TB co-infection. These findings demonstrate the feasibility of combined ART and anti-TB treatment at primary health care level in low-income countries. This study is registered with clinicaltrial.gov, NCT01433796.

Effectiveness and durability of darunavir/ritonavir (DRV/r) in DRV/r-experienced HIV-1-infected patients in routine clinical practice.

IntroductionThis was a descriptive non-interventional study in HIV-1-infected patients treated with DRV/r conducted in the clinical setting, with a single-arm prospective design. The primary objective was to collect data on utilization of darunavir/ritonavir (DRV/r) under the conditions described in the marketing authorization. Efficacy (measured as viral load [VL] <50 copies/mL and CD4+ cell count) was evaluated for DRV/r in combination with other antiretroviral (ARV) agents in routine clinical practice in Italy.Materials and MethodsHere we describe an analysis of effectiveness and durability data from two cohorts of DRV/r-experienced patients with HIV-1 infection, already receiving DRV/r according to usual clinical practice, collected prospectively from June 2009 to December 2012: Cohort 1, data from patients from the DRV/r Early Access Program (TMC114-C226 study; N=235 patients) and Cohort 2, a separate cohort of ARV-DRV/r-experienced patients (N=407 patients), treated with DRV/r in the market. Patient characteristics are shown in Table 1.ResultsThe median length of DRV/r exposure during the study was 925 days (interquartile range [IQR] 692–1006) in Cohort 1, and 581 (IQR 508–734) days in Cohort 2. Of those patients that completed the study, 94% and 87% of patients were virologically suppressed in Cohort 1 and 2, respectively, at last study visit (LSV). As expected, the virological suppression rate was higher in patients with baseline VL <50 copies/mL (Table 2). Mean CD4+ cell counts improved from baseline to LSV in both cohorts (Cohort 1: +54 cells/µL [95% CI 31, 77] and Cohort 2: +59 cells/µL [95% CI 44, 73]). High persistence rates were seen in both cohorts, with 75.3% of patients in Cohort 1 and 82.6% in Cohort 2 remaining on treatment at LSV; very few patients discontinued due to virologic failure (Table 1). Other reasons for study discontinuation are shown in Table 1. Very few patients changed DRV/r dosing during the study, 15 from 1200 to 800 mg o.d.ConclusionsIn patients already treated with DRV/r, DRV/r-based ARV treatment provided effective viral suppression with long-lasting durability, low virological response failure, low discontinuation rates and good tolerability. These data confirm DRV/r to be an effective treatment choice in previously treated patients.

Outcomes of initial antiretroviral treatment (ART) among recently diagnosed HIV patients in HIV-TR cohort, 2011-2012.

IntroductionHIV-TR is a recently established (2012) multicentre cohort in Turkey. The aim of this study is to analyze epidemiological, immunologic and virologic data of recently diagnosed HIV patients.Materials and MethodsEpidemiologic, clinical and laboratory data of all patients diagnosed in 2011 and 2012 were recorded by a web-based data collection system, retrospectively.ResultsA total of 693 patients (561 male, 132 female) at 24 sites were enrolled. The median age at first presentation for HIV care was 36. The proportion of patients presenting with advanced HIV disease (CD4 count<200/mm3 or presenting with an AIDS-defining event) was 30.6%; and 52.4% of patients were late presenters (CD4 count<350/mm3 or presenting with an AIDS-defining event). Median CD4 counts at presentation and before treatment were 344 (IQR: 175–540) and 295 (IQR: 150–430), respectively. Pretreatment CD4 count was >500 copies/mL in 18.5% of patients. Of 531 patients receiving ART, initial combinations consist of tenofovir/emtricitabine (TDF/FTC) plus efavirenz (EFV) in 48.2% and TDF/FTC plus lopinavir/ritonavir (LPV/r) in 37.5% and other combinations in 14.3% of the patients. Pre-treatment HIV-RNA was over 100.000 copies/mL in 52.3% of patients. At Weeks 24 and 48, HIV-RNA were<50 copies/mL in 63,4% of 385 patients and 82% of 311 patients reported to be still on ART and had a viral load measurement, respectively. Median pretreatment CD4 count was lower for TDF/FTC+LPV/r recipients than TDF/FTC+EFV recipients (250 vs 316) (p<0.05). The median increase from baseline CD4 cell count was 230 in TDF/FTC+LPV/r group, 193 in TDF/FTC+EFV group and 216 among all treated patients. Of 531 patients receiving ART, 11 had died and 19 were lost to follow-up.ConclusionDespite 52.4% of recently diagnosed patients were late presenters; a high rate of virologic suppression was achieved in HIV-TR Cohort. A national HIV testing strategy targeting subpopulations with higher risk is urgently needed.

Simplification to Stribild vs continuation of RTV‐boosted DRV with FTC and TDF in virologically suppressed HIV adults: a STRATEGY‐PI subgroup analysis

IntroductionSimplification to Stribild (STB) was statistically superior to continuation of a ritonavir-boosted protease inhibitor (PI+RTV) with emtricitabine and tenofovir DF (FTC/TDF) at week (W) 48 in virologically suppressed HIV adults (1). We report the W48 efficacy and safety of STB versus RTV-boosted darunavir (DRV) with FTC/TDF in suppressed subjects.Material and MethodsVirologically suppressed subjects on PI+RTV with FTC/TDF regimens for ≥6 months were randomized (2:1) to switch to STB vs continue their PI regimen. Eligibility criteria included no documented resistance to FTC and TDF, no history of virologic failure and eGFR ≥70 mL/min. The primary endpoint was the proportion of subjects in the modified ITT population who maintained HIV-1 RNA <50 copies(c)/mL at W48 by FDA snapshot algorithm (12% non-inferiority margin). Subgroup analysis by PI use (DRV [173], atazanavir [174], lopinavir [72], Other PI [13]) at screening was pre-specified.ResultsFour hundred twenty-nine subjects were randomized and treated (mITT set). In the DRV subgroup, 113 switched to STB; 60 continued a RTV-boosted DRV with FTC/TDF. At W48, 95% STB versus 92% DRV maintained HIV-1 RNA <50 c/mL. No emergent resistance was detected in either group. Median increases from baseline in CD4 count at week 48 (cells/µL): 28 STB versus 29 DRV (p=0.81). Discontinuations due to adverse events were 3% STB versus 2% DRV; one case of isolated decrease in eGFR in the DRV group and no cases of proximal renal tubulopathy in either group. There were statistically significant decreases in the frequency of diarrhoea reported on the HIV Symptom Index at week 4 to week 48 compared to baseline after switching to STB. There was a greater but non-progressive decrease from baseline in eGFR in the STB vs DRV group; median changes (mL/min) at week 48: −8.5 vs −0.6, consistent with the known cobicistat inhibition of renal creatinine secretion. Switch to STB was associated with a higher treatment ease (convenience, flexibility, demand, lifestyle, understanding) score (range: −15 to 15) at week 4 (median: 12 vs 9; p=0.006) and week 24 (median: 13 vs 8; p=0.001).ConclusionsIn this small group of virologically suppressed subjects, simplification to STB versus continuation of a RTV-boosted DRV with FTC/TDF was safe, well-tolerated, and associated with a high rate of virologic suppression at week 48. There was more treatment ease with STB use.

Switch to Stribild versus continuation of NVP or RPV with FTC and TDF in virologically suppressed HIV adults: a STRATEGY-NNRTI subgroup analysis.

IntroductionSwitch to Stribild (STB) was non-inferior to continuation of a non-nucleoside reverse transcriptase inhibitor (NNRTI) with emtricitabine and tenofovir DF (FTC/TDF) at week 48 in virologically suppressed HIV adults [1]. We report the Week 48 efficacy and safety of STB versus nevirapine (NVP) or rilpivirine (RPV) with FTC/TDF in suppressed subjects.Materials and MethodsVirologically suppressed subjects on an NNRTI with FTC/TDF regimens for ≥6 months were randomized (2:1) to switch to STB versus continue their NNRTI regimen. Eligibility criteria included no documented resistance to FTC and TDF, no history of virologic failure and eGFR ≥70 mL/min. The primary endpoint was the proportion of subjects in the modified ITT population who maintained HIV-1 RNA <50 copies(c)/mL at Week 48 by FDA snapshot algorithm (12% non-inferiority margin). Subgroup analysis by non-EFV NNRTI use (NVP [74]; RPV [19]; etravirine [3]) at screening was pre-specified.ResultsThe mITT population included 433 subjects who were randomized and treated. In the non-EFV NNRTI subgroup, 59 switched to STB; 37 continued a non-EFV NNRTI (27 NVP, 10 RPV) with FTC/TDF. At week 48, 97% STB versus 95% non-EFV NNRTI maintained HIV-1 RNA <50 c/mL. No emergent resistance was detected in either group. No difference in median increases from baseline in CD4 count at week 48 (cells/µL): 25 STB versus 55 non-EFV NNRTI (p=0.78). No discontinuation due to adverse events; no cases of proximal renal tubulopathy. As expected, there were no significant changes in the frequency of neuropsychiatric symptoms (i.e. anxiety, insomnia, dizziness, vivid dreams, weird/intense dreams, and nightmares) reported on the HIV Symptom Index at week 48 compared to baseline after switching to STB. There was a greater but non-progressive decrease from baseline in eGFR in the STB versus non-EFV NNRTI group; median changes (mL/min) at week 48: −9.1 versus −1.4. Switch to STB was associated with a higher treatment ease (convenience, flexibility, demand, lifestyle, understanding) score (range: −15 to 15) at week 4 (median: 14 vs 11; p=0.047) and week 24 (median: 14 vs 12.5; p=0.038).ConclusionsIn this small group of virologically suppressed subjects, switch to STB vs continuation of NVP or RPV with FTC/TDF was safe, well-tolerated, and associated with a high rate of virologic suppression at week 48. There was more treatment ease with STB use.

Novel Single-Tablet Regimen Effective as Initial Treatment of HIV

The first single-tablet regimen containing an integrase inhibitor for the treatment of human immunodeficiency virus demonstrated high rates of virologic suppression, safety, and tolerability at 144 weeks in treatment-naïve patients. This article presents the results of the prespecified pooled analysis from 2 double-blind, active-control phase 3 studies of first-line treatment.

Evaluation of treatment outcomes for patients on first-line regimens in US President's Emergency Plan for AIDS Relief (PEPFAR) clinics in Uganda: predictors of virological and immunological response from RV288 analyses.

Viral load (VL) monitoring is recommended, but seldom performed, in resource-constrained countries. RV288 is a US President's Emergency Plan for AIDS Relief (PEPFAR) basic programme evaluation to determine the proportion of patients on treatment who are virologically suppressed and to identify predictors of virological suppression and recovery of CD4 cell count. Analyses from Uganda are presented here. In this cross-sectional, observational study, patients on first-line antiretroviral therapy (ART) (efavirenz or nevirapine+zidovudine/lamivudine) from Kayunga District Hospital and Kagulamira Health Center were randomly selected for a study visit that included determination of viral load (HIV-1 RNA), CD4 cell count and clinical chemistry tests. Subjects were recruited by time on treatment: 6-12, 13-24 or >24 months. Logistic regression modelling identified predictors of virological suppression. Linear regression modelling identified predictors of CD4 cell count recovery on ART. We found that 85.2% of 325 subjects were virologically suppressed (viral load<47 HIV-1 RNA copies/ml). There was no difference in the proportion of virologically suppressed subjects by time on treatment, yet CD4 counts were higher in each successive stratum. Women had higher median CD4 counts than men overall (406 vs. 294 cells/μL, respectively; P<0.0001) and in each time-on-treatment stratum. In a multivariate logistic regression model, predictors of virological suppression included efavirenz use [odds ratio (OR) 0.47; 95% confidence interval (CI) 0.22-1.02; P=0.057], lower cost of clinic visits (OR 0.815; 95% CI 0.66-1.00; P=0.05), improvement in CD4 percentage (OR 1.06; 95% CI 1.014-1.107; P=0.009), and care at Kayunga vs. Kangulamira (OR 0.47; 95% CI 0.23-0.92; P=0.035). In a multivariate linear regression model of covariates associated with CD4 count recovery, time on highly active antiretroviral therapy (ART) (P<0.0001), patient satisfaction with care (P=0.038), improvements in total lymphocyte count (P<0.0001) and haemoglobin concentration (P=0.05) were positively associated, whereas age at start of ART (P=0.0045) was negatively associated with this outcome. High virological suppression rates are achievable on first-line ART in Uganda. The odds of virological suppression were positively associated with efavirenz use and improvements in CD4 cell percentage and total lymphocyte count and negatively associated with the cost of travel to the clinic. CD4 cell reconstitution was positively associated with CD4 count at study visit, time on ART, satisfaction with care at clinic, haemoglobin concentration and total lymphocyte count and negatively associated with age.

Cobicistat: a guide to its use as a pharmacokinetic enhancer of atazanavir and darunavir in HIV-1 infection

Oral cobicistat (Tybost™), a selective CYP3A inhibitor without intrinsic anti-HIV activity, is an emerging alternative to ritonavir for the pharmacokinetic enhancement of protease inhibitors (PIs) in adults with HIV-1 infection. Relative to low-dose ritonavir, cobicistat has a lower potential for drug interactions, provides bioequivalent PI exposure, is associated with noninferior virological suppression rates, has a similar tolerability profile and is more soluble, making co-formulation with antiretroviral drugs easier.

Antiretroviral therapy and efficacy after virologic failure on first-line boosted protease inhibitor regimens.

Virologic failure (VF) on a first-line ritonavir-boosted protease inhibitor (PI/r) regimen is associated with low rates of resistance, but optimal management after failure is unknown. The analysis included participants in randomized trials who experienced VF on a first-line regimen of PI/r plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) and had at least 24 weeks of follow-up after VF. Antiretroviral management and virologic suppression (human immunodeficiency virus type 1 [HIV-1] RNA <400 copies/mL) after VF were assessed. Of 209 participants, only 1 participant had major PI-associated treatment-emergent mutations at first-line VF. The most common treatment approach after VF (66%) was to continue the same regimen. The virologic suppression rate 24 weeks after VF was 64% for these participants, compared with 72% for those who changed regimens (P = .19). Participants remaining on the same regimen had lower NRTI resistance rates (11% vs 30%; P = .003) and higher CD4(+) cell counts (median, 275 vs 213 cells/µL; P = .005) at VF than those who changed. Among participants remaining on their first-line regimen, factors at or before VF significantly associated with subsequent virologic suppression were achieving HIV-1 RNA <400 copies/mL before VF (odds ratio [OR], 3.39 [95% confidence interval {CI}, 1.32-8.73]) and lower HIV-1 RNA at VF (OR for <10 000 vs ≥10 000 copies/mL, 3.35 [95% CI, 1.40-8.01]). Better adherence after VF was also associated with subsequent suppression (OR for <100% vs 100%, 0.38 [95% CI, .15-.97]). For participants who changed regimens, achieving HIV-1 RNA <400 copies/mL before VF also predicted subsequent suppression. For participants failing first-line PI/r with no or limited drug resistance, remaining on the same regimen is a reasonable approach. Improving adherence is important to subsequent treatment success.

Abacavir/lamivudine plus darunavir/ritonavir in routine clinical practice: a multicentre experience in antiretroviral therapy-naive and -experienced patients

To present clinical experience with a regimen including abacavir/lamivudine + darunavir/ritonavir in a cohort of HIV-1-infected patients. A retrospective, multicentre cohort study, including all consecutive adult HIV-1-infected patients who started abacavir/lamivudine + darunavir/ritonavir from April 2008 to December 2010 and had at least one follow-up visit. The primary endpoint was HIV-1 viral load (VL) <40 copies/mL at week 48. One hundred and eighty-three patients (42 naive and 141 experienced) from 19 hospitals in Spain were studied. The median follow-up was 26.7 (0.5-58.6) months, 79.8% were men, the median age was 47.1 (21.4-80.5) years, 26.2% had AIDS and 38.8% were positive for hepatitis C virus. At baseline, the median CD4 count was 246 cells/mm(3) in naive patients and 393 cells/mm(3) in experienced patients and the median VL was 4.80 and <1.59 log copies/mL, respectively. At week 48, 81.8% of naive patients and 84.2% of experienced patients receiving the regimen reached a VL <40 copies/mL, whereas at 96 weeks this occurred in 90.5% and 92.8%, respectively. CD4 cell count increases at 48 and 96 weeks were +176.5 and +283.5 cells/mm(3) in naive patients and +74.9 and +93 cells/mm(3) in experienced patients, respectively. Overall, 86 (47%) patients discontinued the study regimen, in many cases possibly related to non-medical reasons, such as drug switches to reduce cost or changes in address due to economic constraints. Three patients died of causes unrelated to therapy and 19 (10.4%) discontinued the regimen due to adverse events. In our cohort, abacavir/lamivudine + darunavir/ritonavir was safe, well tolerated and achieved high rates of virological suppression. In a proportion of patients, discontinuation of this effective regimen was possibly due to non-medical reasons.

Initial therapy for HIV: can less be more?

Since combination antiretroviral therapy (ART) for HIV became standard of care in the mid-1990s, all recommended initial treatments contain three active drugs: two drugs from the nucleoside reverse transcriptase inhibitor (NRTI) class plus a third active drug with a different mechanism of action—a non-nucleoside reverse transcriptase inhibitor, or a protease inhibitor (typically boosted with ritonavir to improve pharmacokinetics), or an integrase inhibitor. This three-drug approach strikes the right balance between efficacy (as measured by rates of virological suppression) and the issues of toxicity and affordability (more drugs means more side-effects and higher costs).

HIV treatment cascade among transgender women in a San Francisco respondent driven sampling study

ObjectiveMale-to-female transgender women (transwomen) have a disproportionate burden of HIV. We sought to estimate HIV treatment cascade indicators among transwomen in San Francisco.MethodsWe conducted a respondent driven sampling (RDS) study...

Evaluation of Patterns of Liver Toxicity in Patients on Antiretroviral and Anti-Tuberculosis Drugs: A Prospective Four Arm Observational Study in Ethiopian Patients

ObjectivesTo evaluate the incidence, type, severity and predictors of antiretroviral and/or anti-tuberculosis drugs induced liver injury (DILI).MethodsA total of 1,060 treatment naive patients were prospectively enrolled into four treatment groups: HIV patients receiving efavirenz based HAART alone (Arm-1); TB-HIV co-infected patients with CD4≤200 cells/μL, receiving concomitant rifampicin based anti-TB and efavirenz based HAART (Arm-2); TB-HIV co-infected patients with CD4>200 cells/μL, receiving anti-TB alone (Arm-3); TB patients taking rifampicin based anti-TB alone (Arm-4). Liver enzyme levels were monitored at baseline, 1st, 2nd, 4th, 8th, 12th and 24th weeks during treatment. CD4 and HIV viral load was measured at baseline, 24th and 48th weeks. Data were analyzed using multivariate Cox Proportional Hazards Model.ResultsA total of 159 patients (15%) developed DILI with severity grades 1, 2, 3 and 4 of 53.5%, 32.7%, 11.3% and 2.5% respectively. The incidence of cholestatic, hepatocellular or mixed pattern was 61%, 15% and 24%, respectively. Incidence of DILI was highest in Arm-2 (24.2%)>Arm-3 (10.8%)>Arm-1 (8.8%)>Arm-4 (2.9%). Concomitant anti-TB-HIV therapy increased the risk of DILI by 10-fold than anti-TB alone (p<0.0001). HIV co-infection increased the risk of anti-TB DILI by 4-fold (p = 0.004). HAART associated DILI was 3-fold higher than anti-TB alone, (p = 0.02). HAART was associated with cholestatic and grade 1 DILI whereas anti-TB therapy was associated with hepatocellular and grade ≥ 2. Treatment type, lower CD4, platelet, hemoglobin, higher serum AST and direct bilirubin levels at baseline were significant DILI predictors. There was no effect of DILI on immunologic recovery or virologic suppression rate of HAART.ConclusionHAART associated DILI is mainly cholestatic and mild whereas hepatocellular or mixed pattern with high severity grade is more common in anti-tuberculosis DILI. TB-HIV co-infection, disease severity and concomitant treatment exacerbates the risk of DILI.