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Understanding the factors associated with pre-exposure prophylaxis (PrEP) adherence may help in the development of strategies to support, motivate and sustain PrEP use. This study estimated self-reported adherence, described perceived barriers and facilitators and investigated factors associated with adherence to daily oral PrEP among men who have sex with man (MSM) and transgender women after 1 year of PrEP use in Brazil. PrEP Brasil was a prospective, multicentre, open-label demonstration study with MSM and transgender women at high risk for HIV infection. We used logistic regression to evaluate factors associated with complete adherence (not forgetting to take any pills in the past 30 days) at week 48. Of 338 participants included in this analysis, 60% reported complete adherence to daily oral PrEP at week 48. Perceived barriers and facilitators to daily oral PrEP were reported by 38.2% and 98.5%, respectively. The most reported barrier and facilitator were ‘I forgot to take my pills’ (19.2%) and ‘Associate PrEP with a daily activity/task’ (58.6%), respectively. In final multivariable analysis, living in Rio de Janeiro (aOR: 0.38; 95% CI: 0.20–0.73), being transgender women (aOR: 0.22; 95% CI: 0.07–0.73), reporting stimulant use (a OR: 0.40; 95% CI: 0.20–0.80) and having any perceived barriers to daily oral PrEP (aOR: 0.12; 95% CI: 0.07–0.23) were associated with decreased odds of complete adherence. Our findings provide information for developing the best practices to promote PrEP adherence in the Brazilian context.

Because persons who identify across the transgender spectrum (PATS) are a key population in human immunodeficiency virus (HIV) yet are underreported in HIV and cardiovascular research, we aimed to characterize this population within the REPRIEVE global clinical trial (n = 7770). Acceptance of gathering gender identity was high (96%). Participation by PATS was 1.7% overall, 2.4% among natal males, 0.3% among natal females, and varied across geographic regions (from 0% in sub-Saharan Africa to 2.3% in High Income Region). Thirty percent of natal male PATS identified other than transgender. Some characteristics differed by gender. Most notably, 38% of natal male PATS receiving gender-affirming treatment had waist circumference >102 cm (compared with ≤25% in other groups). Given that PATS is a key population, HIV research should routinely report trial participation and outcomes by gender in addition to natal sex, to provide the results needed to optimize medical care to PATS.

Background Pre-Exposure Prophylaxis (PrEP) has demonstrated efficacy in the reduction of sexually transmitted HIV infections. The prolonged use of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) co-formulation (TDF/FTC), however, may result in augmented risk of renal toxicity. We aimed to evaluate changes in the estimated Glomerular Filtration Rate (eGFR) in a real-world population setting of participants enrolled in PrEP Brazil, a 48-week prospective, open-label, demonstration study to assess the feasibility of daily oral TDF/FTC used by men who have sex with men and transgender women at high-risk of HIV infection, all over 18 years old. Methods Kidney function was assessed by serial measurement of serum creatinine and eGFR with the Modification of Diet in Renal Disease Study (MDRD) formula on weeks 4, 12, 24, 36 and 48. Adherence to PrEP was assessed by dosing TDF concentration in dried blood spots at weeks 4 and 48, measured by liquid chromatography-mass spectrometry or mass spectrometry. Results Of 392 participants completing the 48-week follow-up protocol with TDF blood detectable levels and eGFR measures, 43.1% were young adults, of Caucasian ethnic background (57.9%), with BMI below 30 kg/m2, without arterial hypertension. At screening, median eGFR was 93.0 mL/min/1.73 m2. At week 4 follow-up, 90 (23% of the study population) participants presented reductions in eGFR greater than 10 mL/min/1.73 m2 as compared to baseline eGFR, some as large as 59 mL/min/1.73 m2, but with no clinical outcomes (adverse events and renal adverse events) severe enough to demand TDF/FTC discontinuation. A negative relationship was observed between TDF blood levels and eGFR at weeks 4 (r = − 0.005; p Conclusions These results suggest that the renal function profile in individuals on TDF/FTC may be assessed on week 4 and then only annually, allowing a more flexible medical follow-up in primary care centers.

Pre-exposure prophylaxis (PrEP) prevents HIV infection among men who have sex with men (MSM) and transgender women (TGW) who are the groups that presents the high incidence risk in Brazil. This cross-sectional secondary analysis describes possible risk compensation, attitudes, and beliefs regarding the use of PrEP among 723 MSM and TGW evaluated in the PrEP Brazil study pre-screening phase. Possible risk compensation was reported by 31.6% individuals. In the multivariate model, factors that increased the likelihood of possible risk compensation were: self-referring as white vs. Black (AOR 2.05; CI 1.09, 3.85), perceiving high likelihood of getting HIV in next 12 months (AOR 1.78; CI 1.23, 2.56), being less afraid of HIV infection if using PrEP (AOR 1.93; CI 1.19, 3.14), feeling liberated to have more partners if using PrEP (AOR 2.93; CI 1.92, 4.49), and believing closest friends would use PrEP (AOR 2.51; CI 1.1, 5.71). We found that possible risk compensation was more common among individuals who presented high-risk perception for HIV infection, probably reflecting they feel at risk and could benefit from PrEP use.

HIV-1 transmitted drug resistance (TDR) mutations may reduce the efficacy of antiretroviral therapy (ART), but pre-treatment testing to determine the virus genotype can improve the efficacy of ART. Unfortunately, issues related to cost and logistics of pre-treatment testing limit its use in resource-limited settings. We studied 596 ART-naive individuals who were newly diagnosed from 2014 to 2016 in São Paulo, Brazil, to evaluate TDR and virological outcome after 48 weeks of genotype-guided therapy. One or more TDR (based on the WHO surveillance list) was observed in 10.9% (CI 95%, 8.6-13.6) of the sequences, the most common of which was the K103 N mutation, which confers resistance to first-generation drugs of the non-nucleoside reverse transcriptase inhibitor (NNRTI) antiretroviral drug class. Dual-class (1%, 6/596) and triple-class (0.34%, 2/596) resistance were uncommon. After 48 weeks of treatment with ART, infection was suppressed to below 200 copies/mL in most patients (95%), with full suppression (RNA target not detected) in 65%. The following characteristics at patient enrollment were independently associated with a lack of full suppression: CD4 T cell counts below 500 cells/µL, viremia above 100,000 copies/mL, older age, and TDR to NNRTI. The rates of resistance were intermediate, but genotype-guided therapy resulted in high rates of viral suppression. The observed resistance profile should not be an obstacle to the use of the dolutegravir-based regimen now recommended in Brazil, but genotype testing may be warranted before initiating first-generation NNRTI-based regimens.

Objectives To determine the impact of valaciclovir on HIV disease progression in treatment-naive HIV-positive adults. Methods In this fully blind, multicentre, 1:1 randomized placebo-controlled trial, treatment-naive HIV-1-positive adults with CD4 counts 400–900 cells/mm3 and not meeting contemporaneous recommendations for combination ART (cART) were randomized to valaciclovir 500 mg or placebo twice daily, and followed quarterly until having two consecutive CD4 counts ≤350 cells/mm3 or initiating cART for any reason. The primary analysis compared the rate of CD4 count decline by study arm after adjusting for baseline CD4 count and viral load (VL). Secondary analyses compared the rate of CD4 percentage decline, HIV VL, herpes simplex virus (HSV) recurrences and drug-related adverse events. The trial closed after release of the START trial results in August 2015. Results We enrolled 198 participants in Canada, Brazil, Argentina and the UK. Median (IQR) age was 35 (30–43) years. Baseline CD4 count was 592 (491–694) cells/mm3 and VL was 4.04 (3.5–4.5) log10 copies/mL. Over 276 person-years of follow-up, CD4 counts declined by 49 cells/mm3/year in the valaciclovir arm versus 58 cells/mm3/year in the placebo arm (P = 0.65). No differences were seen in the rate of change in CD4 percentage (−1.2%/year versus −1.7%/year, P = 0.34). VL was 0.27 log10 copies/mL lower in valaciclovir participants overall (P

IntroductionEfficacy of daily emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) for PrEP is strongly dependent on the adherence. We examined the concordance between indirect adherence measures and protective drug levels among participants retained through 48 weeks in the PrEP Brasil Study.MethodsPrEP Brasil was a prospective, multicenter, open-label demonstration project evaluating PrEP provision for men who have sex with men (MSM) and transgender women (TGW) at higher risk for HIV infection within the setting of Brazilian Public Health System. Three indirect adherence measures were obtained at week 48: medication possession ratio (MPR), pill count and self-report (30-days recall). Tenofovir diphosphate (TFV-DP) concentration in Dried Blood Spot (DBS) was measured at week 48. Areas under (AUC) the receiver operating characteristics (ROC) curve were used to evaluate the concordance between achieving protective drug levels (TFV-DP≥700fmol/punch) and the indirect adherence measures. Youden's index and distance to corner were used to determine the optimal cutoff points for each indirect adherence measure. We calculated sensitivity, specificity, negative (NPV) and positive (PPV) predictive values for the found cutoff points. Finally, Delong test was used to compare AUCs.Results and discussionFrom April, 2014 to July, 2016, 450 participants initiated PrEP, 375(83.3%) were retained through 48 weeks. Of these, 74% (277/375) had TFV-DP ≥700fmol/punch. All adherence measures discriminated between participants with and without protective drug levels (AUC>0.5). High indirect adherence measure was predictive of protective drug levels (PPV>0.8) while low indirect adherence measure was not predictive of lack of protective drug levels (NPVConclusionsLow-burden measurements such as MPR and self-report can be used to predict PrEP adherence in a public health context in Brazil for MSM and TGW retained through 48 weeks. Clinical Trial Number: NCT01989611.

Antiretroviral pre-exposure prophylaxis (PrEP) is recommended to prevent HIV infection among high-risk men who have sex with men (MSM) though not available in Brazil where the HIV epidemic persists unabated in this group. This cross-sectional study describes PrEP awareness and willingness and associated factors among MSM and transvestite/transgender women (trans women) pre-screened for the PrEP Brasil study. Awareness was reported by 61.3 % of the participants and was associated with age, education, site, study period and prior HIV testing. Most participants (82.1 %) were willing to use PrEP, which was associated with site, study period, number of male condomless anal sexual partners and anal sex with HIV positive/unknown partners. PrEP information is need among young and less educated individuals. Willingness to use PrEP was high and future studies should be conducted to confirm PrEP acceptability and the characteristics of the population who chose to adopt this intervention.

Increased access to successful antiretroviral therapy (ART) is necessary in order to achieve an AIDS-free generation. Importantly, slightly over half of the people living with HIV are women. Small studies have described many barriers to accessing treatment and care among women living with HIV. This cross-sectional, non-interventional, epidemiological study assessed the prevalence of barriers to accessing care for women living with HIV across 27 countries, divided into four global regions. HIV-positive women attending routine clinical visits were offered the opportunity to participate in the study. Data describing the study sites and demographic characteristics of the participating women were collected. Participating women filled out questionnaires including the Barriers to Care Scale (BACS) questionnaire, on which they reported the extent to which they found each of the 12 potential barriers to accessing health care problematic. A total of 1931 women living with HIV were included in the study: 760 from Western Europe and Canada (WEC), 532 from Central and Eastern Europe (CEE), 519 from Latin America (LA), and 120 from China. The mean age of participating women was 40.1 ± 11.4 years. A total of 88.2% were currently taking ART. A total of 81.8% obtained HIV treatment under a government health plan. The most prevalent barrier to care was community HIV/AIDS stigma. Community HIV/AIDS knowledge, lack of supportive/understanding work environments, lack of employment opportunities, and personal financial resources were also highly prevalent barriers to accessing care. These findings indicate that, more than 30 years after the start of the AIDS epidemic, stigma is still a major issue for women living with HIV. Continued efforts are needed to improve community education on HIV/AIDS in order to maximize access to health care among women living with HIV.

Background Concurrent psychosocial problems may synergistically increase the risk of HIV infection (syndemics), representing a challenge for prevention. We aimed to evaluate the prevalence and associated factors of syndemics among men who have sex with men (MSM) and transgender women (TGW) enrolled in the Brazilian pre-exposure prophylaxis demonstration study (PrEP Brasil Study). Methods Secondary cross-sectional analysis of the PrEP Brasil Study was performed. Of 450 HIV-seronegative MSM/TGW enrolled in the PrEP Brasil Study– conducted at Rio de Janeiro and Sao Paulo, Brazil– 421 participants with complete data were included in the present analysis. Syndemics was defined as occurrence of ≥2 of the following conditions: polysubstance (≥2) use, binge drinking, positive depression screen, compulsive sexual behavior, and intimate partner violence (IPV). Results The prevalence of recent polysubstance use was 22.8%, binge drinking 51.1%, positive depression screening 5.2%, compulsive sexual behavior 7.1%, and IPV 7.3%. Syndemics prevalence was 24.2%, and associated factors were younger age (adjusted Odds Ratio (aOR) 0.95, 95% Confidence Interval (95% CI) 0.92–0.98 per year increase), TGW vs. MSM (aOR 3.09, 95% CI: 1.2–8.0), some college education or more vs. less than college (aOR 2.49, 95% CI: 1.31–4.75), and multiple male sexual partners in prior 3 months (aOR 1.69, 95% CI: 0.92–3.14). Conclusion Given the high prevalence of syndemics, particularly of polysubstance use and binge drinking, PrEP delivery offers an opportunity to diagnose and intervene in mental and social well-being.

PrEP Brasil was a demonstration study to assess feasibility of daily oral tenofovir diphosphate disoproxil fumarate plus emtricitabine provided at no cost to men who have sex with men (MSM) and transgender women at high risk for HIV within the Brazilian public health system. We report week 48 pre-exposure prophylaxis (PrEP) retention, engagement, and adherence, trends in sexual behaviour, and incidence of HIV and sexually transmitted infections in this study cohort.PrEP Brasil was a 48 week, open-label, demonstration study that assessed PrEP delivery at three referral centres for HIV prevention and care in Rio de Janeiro, Brazil (Fundação Oswaldo Cruz), and São Paulo, Brazil (Universidade de São Paulo and Centro de Referência e Treinamento em DST e AIDS). Eligible participants were MSM and transgender women who were HIV negative, aged at least 18 years, resident in Rio de Janeiro or São Paulo, and reported one or more sexual risk criteria in the previous 12 months (eg, condomless anal sex with two or more partners, two or more episodes of anal sex with an HIV-infected partner, or history of sexually transmitted infection [STI] diagnosis). Participants were seen at weeks 4, 12, 24, 36, and 48 for PrEP provision, clinical and laboratory evaluation, and HIV testing. Computer-assisted self-interviews were also done at study visits 12, 24, 36, and 48, and assessed sexual behaviour and drug use. PrEP retention was defined by attendance at the week 48 visit, PrEP engagement was an ordinal five-level variable combining presence at the study visit and drug concentrations, and PrEP adherence was evaluated by measuring tenofovir diphosphate concentrations in dried blood spots. Logistic regression models were used to quantify the association of variables with high adherence (≥4 doses per week). The study is registered with ClinicalTrials.gov, number NCT01989611.Between April 1, 2014, and July 8, 2016, 450 participants initiated PrEP, 375 (83%) of whom were retained until week 48. At week 48, 277 (74%) of 375 participants had protective drug concentrations consistent with at least four doses per week: 183 (82%) of 222 participants from São Paulo compared with 94 (63%) of 150 participants from Rio de Janeiro (adjusted odds ratio 1·88, 95% CI 1·06-3·34); 119 (80%) of 148 participants who reported sex with HIV-infected partners compared with 158 (70%) of 227 participants who did not (1·78, 1·03-3·08); 67 (87%) of 77 participants who used stimulants compared with 210 (71%) of 298 participants who did not (2·23, 1·02-4·92); and 232 (80%) of 289 participants who had protective concentrations of tenofovir disphosphate at week 4 compared with 42 (54%) of 78 participants who did not (3·28, 1·85-5·80). Overall, receptive anal sex with the last three partners increased from 45% at enrolment to 49% at week 48 (p=0·17), and the mean number of sexual partners in the previous 3 months decreased from 11·4 (SD 28·94) at enrolment to 8·3 (19·55) at week 48 (p0·0013). Two individuals seroconverted during follow-up (HIV incidence 0·51 per 100 person-years, 95% CI 0·13-2·06); both of these patients had undetectable tenofovir concentrations at seroconversion.Our results support the effectiveness and feasibility of PrEP in a real-world setting. Offering PrEP at public health-care clinics in a middle-income setting can retain high numbers of participants and achieve high levels of adherence without risk compensation in the investigated populations.Brazilian Ministry of Health, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Secretaria de Vigilancia em Saúde, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, and Fundação de Amparo à Pesquisa do Estado de São Paulo.

Introduction : The efficacy of pre-exposure prophylaxis (PrEP) in preventing sexual acquisition of human immunodeficiency virus (HIV) is well established. Little is known about the feasibility of PrEP implementation in middle-income settings with concentrated epidemics among men who have sex with men (MSM) and transgender women (TGW). Methods : PrEP Brasil is a prospective, multicentre, open-label demonstration project assessing PrEP delivery in the context of the Brazilian Public Health System. HIV-uninfected MSM and TGW in 3 referral centres in Rio de Janeiro and Sao Paulo were evaluated for eligibility and offered 48 weeks of daily emtricitabine/tenofovir for PrEP. Concentrations of tenofovir diphosphate in dried blood spot samples (DBS) at week 4 after enrolment (early adherence) were measured. Predictors of drug levels were assessed using ordinal logistic regression models considering the DBS drug level as a 3 level variable (

Concurrent treatment of HIV and tuberculosis is complicated by drug interactions. We explored the safety and efficacy of raltegravir as an alternative to efavirenz for patients co-infected with HIV and tuberculosis.We did a multicentre, phase 2, non-comparative, open-label, randomised trial at eight sites in Brazil and France. Using a computer-generated randomisation sequence, we randomly allocated antiretroviral-naive adult patients with HIV-1 and tuberculosis (aged ≥18 years with a plasma HIV RNA concentration of1000 copies per mL) to receive raltegravir 400 mg twice a day, raltegravir 800 mg twice daily, or efavirenz 600 mg once daily plus tenofovir and lamivudine (1:1:1; stratified by country). Patients began study treatment after the start of tuberculosis treatment. The primary endpoint was virological suppression at 24 weeks (HIV RNA50 copies per mL) in all patients who received at least one dose of study drug (modified intention-to-treat analysis). We recorded death, study drug discontinuation, and loss to follow-up as failures to achieve the primary endpoint. We assessed safety in all patients who received study drugs. This study is registered in ClinicalTrials.gov, number NCT00822315.Between July 3, 2009, and June 6, 2011, we enrolled and randomly assigned treatment to 155 individuals; 153 (51 in each group) received at least one dose of the study drug and were included in the primary analysis. 133 patients (87%) completed follow-up at week 48. At week 24, virological suppression was achieved in 39 patients (76%, 95% CI 65-88) in the raltegravir 400 mg group, 40 patients (78%, 67-90) in the raltegravir 800 mg group, and 32 patients (63%, 49-76) in the efavirenz group. The adverse-event profile was much the same across the three groups. Three (6%) patients allocated to efavirenz and three (6%) patients allocated to raltegravir 800 mg twice daily discontinued the study drugs due to adverse events. Seven patients died during the study (one in the raltegravir 400 mg group, four in the raltegravir 800 mg group, and two in the efavirenz group): none of the deaths was deemed related to study treatment.Raltegravir 400 mg twice daily might be an alternative to efavirenz for the treatment of patients co-infected with HIV and tuberculosis.French National Agency for Research on AIDS and Viral Hepatitis (ANRS), Brazilian National STD/AIDS Program-Ministry of Health.

This subgroup analysis of the phase 3 DUET trials examined the impact of the background regimen on virologic response to etravirine in treatment-experienced patients.Patients received etravirine 200 mg or placebo, both twice daily with a background regimen of darunavir/ritonavir, investigator-selected nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), and optional enfuvirtide. Virologic response at week 48 (viral load50 HIV-1 RNA copies/mL) was analyzed by the number and activity of background agents.Baseline phenotypic sensitivity score (PSS), enfuvirtide use, darunavir fold change in 50% effective concentration (FC), and number of baseline darunavir resistance-associated mutations (RAMs) were significant predictors of response to etravirine (P.0001, P = .0018, P.0001, and P = .0120, respectively). The number of active NRTIs was not a significant predictor of response (P = .0626). The highest response rates in etravirine-treated patients were associated with PSS ≥2, de novo enfuvirtide use, darunavir FC ≤10, ≤1 darunavir RAM, and ≥2 active NRTIs. Virologic response was consistently higher in etravirine-treated patients than placebo-treated patients, regardless of the activity of the background regimen. Response rates according to baseline PSS were 46% to 79% in the etravirine group versus 6% to 75% in the placebo group.The results of this subanalysis demonstrate higher virologic response rates with increased activity of the background regimen in both treatment groups, with the highest responses achieved in patients using ≥2 active agents in addition to etravirine.

Study 903 is a phase 3 trial with a completed 144-week, double-blind phase comparing tenofovir DF (TDF) to stavudine (d4T) in combination with lamivudine (3TC) and efavirenz (EFV) and an ongoing additional 336-week open-label extension phase.Patients in Brazil, Argentina, and the Dominican Republic who completed the 144-week double-blind phase on TDF were eligible to roll over to the extension phase (weeks 144-480). Results from an interim week 288 analysis are presented.Eighty-six patients (62% male, 70% white) initially randomized to the TDF arm continued treatment with TDF. At the end of the 144-week, double-blind phase, 85 of the 86 had HIV-1 RNA400 copies/mL, of whom 84% maintained virologic suppression through week 288. CD4 counts continued to improve with a mean increase of 135 cells/mm(3) from entry into the open-label extension to week 288. No patient discontinued due to renal adverse events. Small changes in bone mineral density at the lumbar spine and hip were seen in the first 48 weeks but were nonprogressive through 288 weeks. Mean limb fat increased from 8.0 kg at week 96 to 8.8 kg at week 288.Through 288 weeks, once-daily TDF+3TC+EFV demonstrated sustained antiretroviral activity with continued immunologic recovery. TDF treatment was not associated with renal adverse events or limb fat loss in antiretroviral-naïve patients.

Maraviroc is a first-in-class chemokine coreceptor type-5 (CCR5) antagonist with demonstrated immunovirologic activity in treatment-experienced (TE) patients with CCR5 (R5)-tropic HIV-1; however, experience in regimens containing newer antiretroviral agents is limited. The primary objective of this 96-week open-label, noncomparative, multicenter Phase 3b study (NCT00478231) was to assess the safety of maraviroc in combination with optimized background therapy (OBT), which could include recently introduced agents such as darunavir and raltegravir in TE patients in Brazil with R5 HIV-1 and limited therapeutic options. Immunovirologic activity was a secondary endpoint. Of 638 patients screened, 206 were treated and 125 completed the study. Approximately 70% were male; the mean age was 43.2 years. Most patients (65.0%) received an OBT combination of protease inhibitor plus nucleoside reverse transcriptase inhibitor. Adverse event (AE) and treatment-related AE incidence was 91.3% and 36.9%, respectively. The most common AEs were diarrhea, nasopharyngitis, and headache. Serious AEs and treatment-related serious AEs occurred in 16.5% and 4.4% of patients. Only eight patients (3.9%) discontinued due to AEs. Few AIDS-defining events were observed (4.9%). The proportion of patients with viral load400 copies/ml increased from 2.4% at baseline to 43.9% at week 8, remaining40% until week 48. At the end of treatment, 26.7% of patients had a viral load400 copies/ml. Median CD4(+) cell count increased throughout the study; the mean change from baseline to end of treatment was 174.1 cells/μl. In conclusion, maraviroc, combined with different agents from multiple classes, was well tolerated in highly TE patients. Maraviroc plus OBT was associated with an immunovirologic response in this population.

Study 903 is a phase 3 trial with a completed 144-week, double-blind phase comparing tenofovir DF (TDF) with stavudine (d4T), in combination with lamivudine (3TC) and efavirenz (EFV), and an ongoing 336-week open-label extension phase.Patients in 3 countries completing the d4T treatment phase were allowed to switch d4T to TDF and receive once-daily TDF+3TC+EFV in the extension phase.At the time of switch, 100% and 99% of patients (n = 85; 60% male, 64% White; mean age 37 years; mean CD4 = 650 cells/mm3) had HIV RNA400 and50 copies/mL. At 144 weeks after the switch, 89% (missing = failure) had HIV RNA400 copies/mL and 87% had HIV RNA50 copies/mL. Mean CD4 cell count increased 155 cells/mm3. No patient had virologic failure. Significant decreases from switch to week 144 in mean fasting total cholesterol (-22 mg/dL, p.0001) and triglycerides (-78 mg/dL, p.0001) were observed. Mean limb fat increased significantly from 4.5 kg to 5.8 kg, 144 weeks after switch (p.0001).In virologically suppressed patients, switching d4T to TDF as part of a once-daily regimen with 3TC and EFV resulted in maintenance of virologic suppression and continued CD4 cell increases through 144 weeks, with significant improvements in metabolic parameters.

BACKGROUND: The protease inhibitor darunavir has been shown to be efficacious in highly treatment-experienced patients with HIV infection, but needs to be assessed in patients with a broader range of treatment experience. We did a randomised, controlled, phase III trial (TITAN) to compare 48-week efficacy and safety of darunavir-ritonavir with that of lopinavir-ritonavir in treatment-experienced, lopinavir-naive patients. METHODS: Patients received optimised background regimen plus non-blinded treatment with darunavir-ritonavir 600/100 mg twice daily or lopinavir-ritonavir 400/100 mg twice daily. The primary endpoint was non-inferiority (95% CI lower limit for the difference in treatment response -12% or greater) for HIV RNA of less than 400 copies per mL in plasma at week 48 (per-protocol analysis). TITAN (TMC114-C214) is registered with ClinicalTrials.gov, number NCT00110877. FINDINGS: Of 595 patients randomised and treated, 187 (31%) were protease inhibitor naive; 476 of 582 (82%) were susceptible to four or more protease inhibitors. At week 48, significantly more darunavir-ritonavir than lopinavir-ritonavir patients had HIV RNA of less than 400 copies per mL (77% [220 of 286] vs 68% [199 of 293]; estimated difference 9%, 95% CI 2-16). Fewer virological failures treated with darunavir-ritonavir than with lopinavir-ritonavir developed primary protease inhibitor mutations (21% [n=6] vs 36% [n=20]) and nucleoside analogue-associated mutations (14% [n=4] vs 27% [n=15]). Safety data were generally similar between the groups; grade 3 or 4 adverse events occurred in 80 (27%) darunavir-ritonavir and 89 (30%) lopinavir-ritonavir patients. INTERPRETATION: In lopinavir-naive, treatment-experienced patients, darunavir-ritonavir was non-inferior to lopinavir-ritonavir treatment in terms of our virological endpoint, and should therefore be considered as a treatment option for this population. Udgivelsesdato: 2007