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Of those in the general population hospitalized for suicidal ideation and suicide attempts in Argentina, many reattempt suicide and are readmitted. However, few studies in Argentina have examined suicidal ideation and suicide-related behaviors among people living with HIV (PLHIV) and none have examined these factors among nonadherent PLHIV, though the prevalence of suicidal ideation in this group may be higher than in the general population and also than in other groups of PLHIV. This study of PLHIV in Buenos Aires, Argentina, examined the correlates of suicidal ideation in nonadherent PLHIV. Nonadherent patients with HIV (N = 118) were recruited from two clinics providing outpatient healthcare services to PLHIV in Buenos Aires, Argentina. Participants completed assessments on demographic characteristics, depression and suicidality, stigma, and self-efficacy. Participants were HIV-infected men (51%) and women (49%) with a median age of 40 years (IQR = 11). About half had completed high school or more, two-thirds were employed, and had a mean monthly income of 4196.79 (SD = 3179.64) Argentine pesos (USD$221). Thirty-three (28% [95% CI 20.3, 37.3]) participants reported suicidal ideation in the past two weeks, and one-third (35.6% [27.1, 44.9]) reported lifetime suicidal ideation. In bivariate analyses, attending a public clinic, being female, younger, unemployed, and experiencing greater stigma and depression were associated with suicidal ideation. In multivariable logistic regression, stigma interacted with the number of years since HIV diagnosis to predict suicidal ideation. The impact of stigma on suicidal ideation decreased with time since HIV diagnosis, suggesting that suicidal ideation may arise following HIV diagnosis due to perception of HIV-related stigma. Interventions to reduce perceived stigma during the period following HIV diagnosis may reduce suicidal ideation in this population. Organizational initiatives that explore HIV stigma microagressions in the healthcare setting may be needed to optimize health outcomes.

Summary Combination antiretroviral therapy (ART), also known as highly active antiretroviral therapy, provides clinical and immunological benefits for people living with HIV and is an effective strategy to prevent HIV transmission at the individual level. Early initiation of ART as part of a test and treat approach might decrease HIV transmission at the population level, but to do so the HIV continuum of care, from diagnosis to viral suppression, should be optimised. Access to ART has improved greatly in Latin America, and about 600 000 people are on treatment. However, health-care systems are deficient in different stages of the HIV continuum of care, and in some cases only a small proportion of individuals achieve the desired outcome of virological suppression. At present, data for most Latin American countries are not sufficient to build reliable metrics. Available data and estimates show that many people living with HIV in Latin America are unaware of their status, are diagnosed late, and enter into care late. Stigma, administrative barriers, and economic limitations seem to be important determinants of late diagnosis and failure to be linked to and retained in care. Policy makers need reliable data to optimise the HIV care continuum and improve individual-based and population-based outcomes of ART in Latin America.

Fil: Suarez, Guadalupe Veronica. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Biomedicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomedicas en Retrovirus y Sida; Argentina

Background This study aimed to evaluate trends and predictors of survival after cancer diagnosis in persons living with HIV in the Caribbean, Central, and South America network for HIV epidemiology cohort. Methods Demographic, cancer, and HIV-related data from HIV-positive adults diagnosed with cancer ≤ 1 year before or any time after HIV diagnosis from January 1, 2000-June 30, 2015 were retrospectively collected. Cancer cases were classified as AIDS-defining cancers (ADC) and non-AIDS-defining cancers (NADC). The association of mortality with cancer- and HIV-related factors was assessed using Kaplan-Meier curves and Cox proportional hazards models stratified by clinic site and cancer type. Results Among 15,869 patients, 783 had an eligible cancer diagnosis; 82% were male and median age at cancer diagnosis was 39 years (interquartile range [IQR]: 32–47). Patients were from Brazil (36.5%), Argentina (19.9%), Chile (19.7%), Mexico (19.3%), and Honduras (4.6%). A total of 564 ADC and 219 NADC were diagnosed. Patients with NADC had similar survival probabilities as those with ADC at one year (81% vs. 79%) but lower survival at five years (60% vs. 69%). In the adjusted analysis, risk of mortality increased with detectable viral load (adjusted hazard ratio [aHR] = 1.63, p = 0.02), age (aHR = 1.02 per year, p = 0.002) and time between HIV and cancer diagnoses (aHR = 1.03 per year, p = 0.01). Conclusion ADC remain the most frequent cancers in the region. Overall mortality was related to detectable viral load and age. Longer-term survival was lower after diagnosis of NADC than for ADC, which may be due to factors unrelated to HIV.

Summary Background Once daily regimens are preferred for HIV-1 treatment, to facilitate adherence and improve quality of life. We compared a new once daily formulation of raltegravir to the currently marketed twice daily formulation. Methods In this randomised, double-blind, parallel-group, phase 3, non-inferiority study, we enrolled participants aged 18 years or older with HIV-1 RNA of 1000 or more copies per mL and no previous antiretroviral treatment at 139 sites worldwide. We randomly assigned participants (2:1) via an interactive voice and web response system to raltegravir 1200 mg (two 600 mg tablets) orally once daily or raltegravir 400 mg (one tablet) orally twice daily, each with tenofovir disoproxil fumarate and emtricitabine orally once daily, for up to 96 weeks. A computer-generated allocation schedule stratified randomisation by screening HIV-1 RNA value and co-infection with hepatitis B or C. Participants, sponsor personnel, investigators, and study site personnel involved in the treatment or evaluation of the participants were unaware of the treatment group assignments. The primary endpoint was the proportion of participants with HIV-1 RNA less than 40 copies per mL at week 48 assessed with the US Food and Drug Administration Snapshot algorithm. Non-inferiority was concluded if the lower bound of the two-sided 95% CI was greater than −10%. We assessed efficacy and safety in all participants who received one dose or more of study treatment. This study is registered with ClinicalTrials.gov, number NCT02131233. Findings Between May 26, 2014, and Dec 5, 2014, 802 participants were enrolled and randomly assigned, 533 to once daily treatment and 269 to twice daily; 797 received study therapy, 531 once daily and 266 twice daily. At week 48, 472 (89%) of 531 once daily recipients and 235 (88%) of 266 twice daily recipients achieved HIV-1 RNA less than 40 copies per mL (treatment difference 0·5%, 95% CI −4·2 to 5·2). Drug-related adverse events occurred in 130 (24%) of 531 participants in the once daily group (one of which was serious; none led to treatment discontinuation) and 68 (26%) of 266 participants in the twice daily group (two of which were serious; two led to treatment discontinuation). The most common drug-related adverse events were nausea (39 [7%] vs 18 [7%]), headache (16 [3%] vs 12 [5%]), and dizziness (12 [2%] vs eight [3%]). No treatment-related deaths were reported. Interpretation A once daily raltegravir 1200 mg regimen was non-inferior compared with raltegravir 400 mg twice daily for initial treatment of HIV-1 infection. These results support the use of raltegravir 1200 mg once daily for first-line therapy. Funding Merck & Co, Inc.

INTRODUCTION: Globally, prosecutions for non-disclosure, exposure or transmission of HIV frequently relate to sexual activity, biting, or spitting. This includes instances in which no harm was intended, HIV transmission did not occur, and HIV transmission was extremely unlikely or not possible. This suggests prosecutions are not always guided by the best available scientific and medical evidence. DISCUSSION: Twenty scientists from regions across the world developed this Expert Consensus Statement to address the use of HIV science by the criminal justice system. A detailed analysis of the best available scientific and medical research data on HIV transmission, treatment effectiveness and forensic phylogenetic evidence was performed and described so it may be better understood in criminal law contexts. Description of the possibility of HIV transmission was limited to acts most often at issue in criminal cases. The possibility of HIV transmission during a single, specific act was positioned along a continuum of risk, noting that the possibility of HIV transmission varies according to a range of intersecting factors including viral load, condom use, and other risk reduction practices. Current evidence suggests the possibility of HIV transmission during a single episode of sex, biting or spitting ranges from no possibility to low possibility. Further research considered the positive health impact of modern antiretroviral therapies that have improved the life expectancy of most people living with HIV to a point similar to their HIV-negative counterparts, transforming HIV infection into a chronic, manageable health condition. Lastly, consideration of the use of scientific evidence in court found that phylogenetic analysis alone cannot prove beyond reasonable doubt that one person infected another although it can be used to exonerate a defendant. CONCLUSIONS: The application of up-to-date scientific evidence in criminal cases has the potential to limit unjust prosecutions and convictions. The authors recommend that caution be exercised when considering prosecution, and encourage governments and those working in legal and judicial systems to pay close attention to the significant advances in HIV science that have occurred over the last three decades to ensure current scientific knowledge informs application of the law in cases related to HIV. ispartof: JOURNAL OF THE INTERNATIONAL AIDS SOCIETY vol:21 issue:7 ispartof: location:Switzerland status: published

Summary Background Doravirine is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) with a pharmacokinetic profile supporting once-daily dosing, and potent in-vitro activity against the most common NNRTI-resistant HIV-1 variants. We compared doravirine with ritonavir-boosted darunavir, when both were given with two nucleoside reverse transcriptase inhibitors (NRTIs), in adults with previously untreated HIV-1 infection. Methods In this randomised, controlled, double-blind, multicentre, non-inferiority trial, adults with HIV-1 infection were screened and enrolled at 125 clinical centres in 15 countries. Eligible participants (aged ≥18 years) were naive to antiretroviral therapy with plasma HIV-1 RNA of at least 1000 copies per mL at screening. Participants who had previously been treated for a viral infection other than HIV-1, those taking immunosuppressive drugs, and individuals with active acute hepatitis were excluded. Participants were randomly assigned (1:1) via an interactive voice and web response system to receive oral doravirine 100 mg or darunavir 800 mg plus ritonavir 100 mg once daily, with two investigator-selected NRTIs (tenofovir and emtricitabine or abacavir and lamivudine) for up to 96 weeks. Randomisation was stratified by HIV-1 RNA measurements at screening (≤100 000 vs >100 000 copies per mL) and the NRTI pair. Study participants, funding institution staff, investigators, and study site personnel were masked to treatment group assignment. The primary efficacy endpoint was the proportion of participants achieving HIV-1 RNA of less than 50 copies per mL at week 48 defined by the US Food and Drug Administration snapshot algorithm, with non-inferiority established if the lower bound of the two-sided 95% CI for the treatment difference (doravirine minus darunavir) was greater than −10 percentage points. All participants who received at least one dose of study drug were included in the primary efficacy and safety analyses. This trial is active, but not recruiting, and is registered with ClinicalTrials.gov, number NCT02275780. Findings Between Dec 1, 2014, and Oct 20, 2015, 1027 participants were screened for eligibility, of whom 769 participants were randomly assigned to treatment (385 with doravirine and 384 with ritonavir-boosted darunavir). 56 participants discontinued treatment in the doravirine group compared with 71 in the darunavir group, mostly due to loss to follow-up. 383 participants who received doravirine and 383 who received darunavir were included in the primary efficacy analyses. At week 48, 321 (84%) participants in the doravirine group and 306 (80%) in the darunavir group achieved plasma HIV-1 RNA of less than 50 copies per mL (difference 3·9%, 95% CI −1·6 to 9·4), indicating non-inferiority of the doravirine regimen. The most common study drug-related adverse events were diarrhoea (21 [5%] of 383 participants in the doravirine group and 49 [13%] of 383 participants in the darunavir group), nausea (25 [7%] vs 29 [8%]), and headache (23 [6%] vs ten [3%]). 18 participants (six [2%] of 383 participants in the doravirine group vs 12 [3%] of 383 participants in the darunavir group) discontinued treatment due to adverse events, which were considered drug-related in four (1%) participants in the doravirine group and 8 (2%) participants in the darunavir group. Serious adverse events occurred in 19 (5%) of 383 participants in the doravirine group and 23 (6%) of 383 in the darunavir roup, and were considered study-drug related in one ( Interpretation In treatment-naive adults with HIV-1 infection, doravirine combined with two NRTIs might offer a valuable treatment option for adults with previously untreated HIV-1 infection. Funding Merck & Co.

Introduction The “greying” of the HIV epidemic necessitates a better understanding of the healthcare needs of older HIV‐positive adults. As these individuals age, it is unclear whether comorbidities and their associated therapies or the ageing process itself alter the response to antiretroviral therapy (ART). In this study, HIV treatment outcomes and corresponding risk factors were compared between older ART initiators and those who were younger using data from the Caribbean, Central and South America Network for HIV Epidemiology (CCASAnet). Methods HIV‐positive adults (≥18 years) initiating ART at nine sites in Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru were included. Patients were classified as older (≥50 years) or younger (

Background Globally, Latin America ranks third among regions with most cases of AIDS related cryptococcal meningitis. In 2009, a lateral flow immunoassay (LFA) for the detection of cryptococcal antigen (CrAg) was developed as a potential point-of-care test for diagnosis of cryptococcal infection. In 2011 World Health Organizations recommended on CrAg screening for HIV positive persons with CD4 below 100 cells/μL, followed by preemptive fluconazole treatment. However, in Argentina no formal recommendations for CrAg screening have been issued. Methods HIV positive patients > = 18 years with advanced immunosuppression (CD4 counts ≤100 cells/μL within 3 months or WHO stage III/IV), who visited the hospital between April 1, 2014 and January 31, 2015, were included. The LFA was performed according to the manufacturer's instructions on all serum samples. When CrAg detection was positive, a lumbar puncture was performed to rule out cryptococcal meningitis. Patients without evidence of meningeal involvement were treated with preemptive oral fluconazole in ambulatory care. Results We included 123 patients. Prevalence of CrAg-positivity was 8.1%. Among the 10 CrAg-positive patients, 6 had meningeal involvement detected through the CSF analysis (CSF India-ink testing, CSF CrAg and culture). The remaining 4 patients with positive CrAg received targeted preemptive treatment with oral fluconazole and were free of cryptococcal disease during the follow-up period. None of the 113 patients with a negative CrAg test result developed cryptococcal disease. Conclusions This is the first study in Argentina, to our knowledge, describing the prevalence of cryptococcosis and usefulness of CrAg screening. LFA provided early diagnosis to determine a high prevalence of CrAg in our hospital, and that screening for subclinical infection with preemptive antifungal treatment, prevented a substantial proportion of meningeal disease.

Purpose of review The review addresses the role of dolutegravir (DTG) in first-line therapy. In the era of test and treat, where United Nations AIDS Program and WHO have set the ambitious targets of 90/90/90, new efficacious, well tolerated, and simple therapeutic options are needed. Recent findings DTG has been tested in large clinical trials in treatment-naive patients, showing noninferiority to raltegravir and superiority compared with efavirenz and ritonavir-boosted darunavir, respectively. The main features of DTG are reviewed in this study, including efficacy, safety, high-resistance barrier, daily treatment schedule, and coformulation as single-tablet regimen. Use of DTG in special populations is also reviewed. Tolerability, with focus in neuropsychiatric disturbances is discussed in particular. DTG has shown high efficacy level, tested in males and females, has no limitations in patients with renal and/or hepatic impairment and is available as single drug (to be combined with two nucleoside reverse transcriptase inhibitors in fixed combinations) or as a single-tablet regimen combined with abacavir and lamivudine. Summary DTG is an excellent candidate for initial therapy in HIV-infected patients. If safety of DTG in pregnant women are confirmed by ongoing studies, DTG might become the first option in WHO antiretroviral guidelines.

Introduction : A proof-of-concept study was designed to evaluate the antiviral efficacy, safety and tolerability of a two-drug regimen with dolutegravir 50 mg once daily (QD) plus lamivudine 300 mg once daily as initial highly active antiretroviral therapy (HAART) among antiretroviral (ARV)-naive patients. Methods : PADDLE is a pilot study including 20 treatment-naive adults. To be selected, participants had no IAS-USA-defined resistance, HIV-1 RNA ≤100,000 copies/mL at screening and negative HBsAg. Plasma viral load (pVL) was measured at baseline; days 2, 4, 7, 10, 14, 21 and 28; weeks 6, 8 and 12; and thereafter every 12 weeks up to 96 weeks. Primary endpoint was the proportion of patients with HIV-1 RNA

AIM To characterize peripheral blood natural killer (NK) cells phenotypes by flow cytometry as potential biomarker of liver fibrosis in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients. METHODS Peripheral mononuclear cells from 24 HIV/HCV (HBV negative) coinfected and 5 HIV/HCV/HBV seronegative individuals were evaluated. HIV/HCV coinfected patients were divided in to groups: G1, patients with METAVIR F0-F2 and G2, patients with METAVIR F3-F4. NK surface cell staining was performed with: Anti-CD3(APC/Cy7), anti-CD56(PE/Cy5), anti-CD57(APC), anti-CD25(PE), anti-CD69(FITC), anti-NKp30(PE), anti-NKp46(PE/Cy7), anti-NKG2D(APC), anti-DNAM(FITC); anti-CD62L (PE/Cy7), anti-CCR7(PE), anti-TRAIL(PE), anti-FasL(PE), anti CD94(FITC). Flow cytometry data acquisition was performed on BD FACSCanto, analyzed using FlowJo software. Frequency of fluorescence was analyzed for all single markers. Clinical records were reviewed, and epidemiological and clinical data were obtained. RESULTS Samples from 11 patients were included in G1 and from 13 in G2. All patients were on ARV, with undetectable HIV viral load. Liver fibrosis was evaluated by transient elastography in 90% of the patients and with biopsy in 10% of the patients. Mean HCV viral load was (6.18 ± 0.7 log10). Even though, no major significant differences were observed between G1 and G2 regarding NK surface markers, it was found that patients with higher liver fibrosis presented statistically lower percentage of NK cells than individual with low to mild fibrosis and healthy controls (G2: 5.4% ± 2.3%, G1: 12.6% ± 8.2%, P = 0.002 and healthy controls 12.2% ± 2.7%, P = 0.008). It was also found that individuals with higher liver fibrosis presented lower CD4 LT count than those from G1 (G2: 521 ± 312 cells/μL, G1: 770 ± 205 cells/μL; P = 0.035). CONCLUSION Higher levels of liver fibrosis were associated with lower percentage of NK cells and LTCD4+ count; and they may serve as noninvasive biomarkers of liver damage.

According to evidence from randomized controlled trials and epidemiological data, the antiretroviral treatment (ART) of choice has consisted of the combination of 2 nucleoside analog reverse-transcriptase inhibitors (NRTI) plus 1 non-nucleoside analog reverse-transcriptase inhibitor (NNRTI) or a protease inhibitor (PI) for more than 17 years. There are several unresolved issues, notably the toxocity associated with NRTI, especially thymidine analogs, and the possibility of cross resistance, which may affect subsequent treatment. The development of new antiretroviral drugs with simpler dosing regimens and lower toxicity has led to evaluation of innovative strategies such as dual therapy for initial ART in treatment-naive, with the aim of preventing long-term toxicity and increasing treatment adherence. Despite encouraging results, some combinations have proven unsatisfactory. The strategies with favorable results to date consist of twice-daily lopinavir/ritonavir (LPV/r)-based regimens, those in the PROGRESS (LPV/r + raltegravir) and GARDEL (LPV/r + lamivudine) trials, and the combination of darunavir and raltegravir (NEAT 001 trial), although the latter observed a higher tendency (statistically nonsignificant) to virological failure in the dual combination arm. These trials were based on the use of NRTI-sparing regimens consisting of 2-3 fully- active agents for highly-active ART in treatment-naive HIV-positive patients. Recent studies provide evidence supporting the use of NRTI-sparing regimens in HIV-infected patients with failure to an initial NNRTI-based ART regimen. The present review will discuss only LPV/r-based innovative strategies in initial ART regimens.

Highly-active antiretroviral therapy (HAART) has been one of the major advances in medicine in the 20th century. Millions of lives have been saved all over the world since triple drug combinations were adopted as the standard of care for HIV disease. First-line regimens may fail, generate side effects, and long term toxicities. In the past, HAART regimens were also complex and difficult to adhere to. So, second line regimens were necessary to preserve the main goal of ARV therapy: suppression viral replication and restoration of the immune system in order to keep patients alive and healthy. From a public health perspective, the impact of HIV treatment as prevention highlights the importance of having safe and effective second line options for patients unable to maintain full viral suppression with first line therapy. New strategies with effective, tolerable drugs are essential components of these regimens. The gap between wealthy and developing countries is particularly evident in the second line scenario.

Objectives PIANO (Paediatric study of Intelence As an NNRTI Option; TMC125-C213; NCT00665847) assessed the safety/tolerability, antiviral activity and pharmacokinetics of etravirine plus an optimized background regimen (OBR) in treatment-experienced, HIV-1-infected children (≥ 6 to 95% adherent by questionnaire and 39% by pill count. Forty-one patients experienced virological failure (VF; time-to-loss-of-virological-response non-VF-censored algorithm) (29 nonresponders; 12 rebounders). Of 30 patients with VF with paired baseline/endpoint genotypes, 18 (60%) developed nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations, most commonly Y181C. Mean etravirine area under the plasma concentration–time curve over 12 h (AUC0–12h; 5216 ng h/mL) and C0h (346 ng/mL) were comparable to adult target values. Conclusions Results with etravirine 5.2 mg/kg bid (with OBR) in this treatment-experienced paediatric population and etravirine 200 mg bid in treatment-experienced adults were comparable. Etravirine is an NNRTI option for treatment-experienced paediatric patients.

Background Doravirine is a novel, non-nucleoside reverse-transcriptase inhibitor (NNRTI) that has demonstrated efficacy in two Phase 3 trials in treatment-naïve adults with HIV-1. Methods This open-label, active-controlled, noninferiority (NI) trial evaluated a once-daily single-tablet regimen of doravirine 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg (DOR/3TC/TDF) vs. continuation of current therapy in adults with HIV-1 virologically suppressed for ≥6 months on a stable regimen of two NRTIs plus a boosted protease inhibitor (PI), boosted elvitegravir, or NNRTI. Participants with screening HIV-1 RNA Results A total of 670 participants (447 ISG, 223 DSG) were treated and included in the analyses; 84.5% were male, 76.4% were white, and mean age was 43.3 years. At Week 24, 93.7% (419/447) of ISG vs. 94.6% (211/223) of DSG had HIV-1 RNA Conclusion A once-daily single-tablet regimen of DOR/3TC/TDF demonstrated non-inferior efficacy and acceptable safety compared with continuing therapy, and is an option for maintaining viral suppression in patients considering a change in therapy. Disclosures P. Kumar, Merck, Pfizer, Janssen,: Grant Investigator and Shareholder, Research grant. GSK, Gilead, Teratechnologies, TaiMed,: Grant Investigator, Scientific Advisor and Shareholder, Consulting fee and Research grant. J. M. Molina, Merck GIlead ViiV Janssen Teva: Ad Board and Speaker’s Bureau, Consulting fee. Gilead Sciences: Grant Investigator, Research support. G. Rizzardini, ViiV, Gilead Science, MSD, Angelini, and Abbvie: Board Member and Speaker’s Bureau, Speaker honorarium. Gliead, ViiV, and MSD: Research Contractor, Research grant. P. Cahn, Abbvie: Grant, Research grant. Merck: Grant, Advisory Board. ViiV Healthcare: Grant, Advisory Board. M. Bickel, Merck & Co., Inc.: Research Contractor, Research grant. Y. Zhou, Merck & Co., Inc.: Employee, Salary. C. Morais, Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc.: Employee and Shareholder, May hold stock/stock options in the company and Salary. S. Kumar, Merck & Co., Inc.: Employee and Shareholder, Salary. P. Sklar, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.: Employee and Shareholder, Salary. G. J. Hanna, Merck Sharp & Dohme, a subsidiary of Merck & Co., inc.: Employee and Shareholder, May hold stock/stock options in the company. and Salary. C. Hwang, Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc.: Employee and Shareholder, Salary. W. Greaves, Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc.: Employee, May hold stock/stock options within the company.

Background DOR is a novel NNRTI that has shown noninferior efficacy to DRV+r- and EFV-based regimens in phase 3 trials (DRIVE-FORWARD [NCT02275780] and DRIVE-AHEAD [NCT02403674]). A prespecified integrated analysis of those trials plus a completed phase 2 trial (P007; NCT01632345) was performed to evaluate the overall safety and tolerability of DOR. Methods In this integrated analysis, DOR (100 mg QD) arms from P007, DRIVE-FORWARD, and DRIVE-AHEAD were compared with DRV+r in DRIVE-FORWARD and EFV in P007 and DRIVE-AHEAD for treatment of HIV-1 in ART-naïve adults. The NRTI background included FTC/TDF in P007, ABC/3TC or FTC/TDF in DRIVE-FORWARD, and 3TC/TDF for DOR and FTC/TDF for EFV in DRIVE-AHEAD. The primary safety endpoint was the proportion of participants discontinuing due to adverse events (AEs) through Week 48. Results A total of 1,710 treated participants were included in the analysis (table). Similar proportions of DOR− and DRV+r-treated participants, and fewer of those treated with DOR than with EFV discontinued due to AEs (2.5% vs. 3.1%, DOR vs. DRV+r; 2.5% vs. 6.6%, DOR vs. EFV). Drug-related AEs (DRAEs) were similar for DOR (30.9%) and DRV+r (32.1%), and higher for EFV (61.4%). The most common DRAEs (≥10% any group, any grade) were dizziness (4.9%, 1.8%, and 30.7%) diarrhea (4.0%, 12.8%, and 5.7%), and abnormal dreams (3.2%, 0.3%, and 10.6%) for DOR, DRV+r, and EFV, respectively. Higher rates of central nervous system (CNS) AEs were reported for DOR when EFV was the comparator, while similar low rates of CNS AEs were reported for DOR when DRV+r was the comparator. In two prespecified analyses combining the DOR 100-mg arms and EFV arms from P007 and DRIVE-AHEAD, 2.8% vs. 6.1% discontinued due to AEs on the DOR- and EFV-treated arms, respectively, for a treatment difference of −3.4% (95% CI: −6.2, −0.8; P = 0.012); 25.0% vs. 55.9% of participants experienced ≥1 neuropsychiatric AE in DOR and EFV arms, respectively. Conclusion At Week 48, DOR was generally safe and well tolerated in ART-naïve adults with HIV-1. Statistically significantly lower proportions of DOR- than EFV-treated participants discontinued due to AEs supported by a lower proportion that discontinued due to DRAEs. Those on DOR had fewer CNS AEs compared with those on EFV, and less diarrhea than those on DRV+r. Disclosures M. Thompson, Merck & Co., Inc.: Research funding to AIDS Research Consortium of Atlanta; no funds to me personally, Research funding to AIDS Research Consortium of Atlanta; no funds to me personally. Bristol Myers Squibb: Research funding to AIDS Research Consortium of Atlanta; no funds to me personally, Research funding to AIDS Research Consortium of Atlanta; no funds to me personally. CytoDyn, Inc.: Research funding to AIDS Research Consortium of Atlanta; no funds to me personally, Research funding to AIDS Research Consortium of Atlanta; no funds to me personally. Gilead Sciences, Inc.: Research funding to AIDS Research Consortium of Atlanta; no funds to me personally, Research funding to AIDS Research Consortium of Atlanta; no funds to me personally. GlaxoSmithKline: Research funding to AIDS Research Consortium of Atlanta; no funds to me personally, Research funding to AIDS Research Consortium of Atlanta; no funds to me personally. Roche Laboratories: Research Funding, Research funding to AIDS Research Consortium of Atlanta; no funds to me personally and Research grant. TaiMed, Inc.: Research Funding, Research funding to AIDS Research Consortium of Atlanta; no funds to me personally and Research grant. ViiV Healthcare: Research Funding, Research funding to AIDS Research Consortium of Atlanta; no funds to me personally. C. Orkin, AbbVie, Abbott, Boehringer Ingelheim, BMS, Gilead, GSK, Janssen, ViiV: Ad Board, Grant Investigator and Research Contractor, Research grant and Research support. J. M. Molina, Merck GIlead ViiV Janssen Teva: Ad Board and Speaker’s Bureau, Consulting fee. Gilead Sciences: Grant Investigator, Research support. J. Gatell, Gilead Sciences: Grant and Independent Contractor, Consulting fee and Educational grant. Janssen: Grant and Independent Contractor, Consulting fee. ViiV Healthcare: Grant and Independent Contractor, Consulting fee. MSD: Grant and Independent Contractor, Consulting fee. P. Sax, Gilead: Consultant and Grant Investigator, Consulting fee, Grant recipient and Research grant. ViiV Healthcare: Consultant and Grant Investigator, Consulting fee, Grant recipient and Research grant. Merck: Consultant and Grant Investigator, Consulting fee, Grant recipient and Research grant. Janssen: Consultant, Consulting fee. BMS, Gilead, Merck, GSK/ViiV: Grant Investigator, Grant recipient and Research grant. P. Cahn, Abbvie: Grant, Research grant. Merck: Grant, Advisory Board. ViiV Healthcare: Grant, Advisory Board. K. Squires, Merck & Co., Inc.: Ad Board, Ad Board. Gilead Sciences: Grant, Ad Board. VIIV: Ad Board, Ad Board. Bristol Myers Squibb: Ad Board, Ad Board. Janssen: Ad Board, Ad Board. Y. Zhou, Merck & Co., Inc.: Employee, Salary. X. Xu, Merck & Co., Inc.: Employee, Salary. A. Rodgers, Merck & Co., Inc.: Employee and Shareholder, Salary. S. Kumar, Merck & Co., Inc.: Employee and Shareholder, Salary. H. Teppler, Merck & Co., Inc.: Employee and Shareholder, Salary. E. Martin, Merck & Co., Inc.: Employee and Shareholder, Salary. G. Hanna, Merck & Co., Inc.: Employee and Shareholder, Salary. C. Hwang, Merck & Co., Inc.: Employee and Shareholder, Salary.

In 1996, the global HIV community gathered in Vancouver, Canada, for the XI International AIDS Conference and shared the clear evidence that triple combination antiretroviral treatment held the power to stem the tide of deaths from AIDS. The HIV treatment era had begun. As we gathered again in Vancouver in July, 2015, it was clear that a new transformative moment is upon us. The Vancouver Consensus statement, which emerged at the recently concluded 8th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2015), signals the scientific affirmation that, rather than limiting access to those who are immune compromised, immediate access to antiretroviral medicines holds the power to rapidly advance the fight to end AIDS.

HIV prevention strategies must be based on evidence of risk behaviours among people with HIV infection. This study aimed to determine the demographic, behavioural and self-reported disease/treatment variables that predict sexual risk behaviour, defined as unprotected intercourse with a partner of unknown or negative HIV status, among HIV-infected outpatients in Buenos Aires, Argentina. Two hundred consecutive outpatients (response rate 76.5%) participated in a self-complete cross sectional survey. The majority (49.5%) identified as heterosexual, and most were on antiretroviral therapy (ART) (75.5%). Undetectable viral load was currently achieved by 63%. Unprotected intercourse with a person of unknown or discordant status in the previous three months was reported by 20%. In multivariate analysis, risk was associated with lower distress from physical symptoms (p=0.012), greater distress from psychological symptoms (p=0.038) and being on treatment had borderline association with risk (p=0.058). The data reveal an important link between self-reported experience of disease, and treatment, with risk. Secondary prevention, care and treatment should not be conducted in isolation from each other if outcomes are to be optimised.

Objective To analyse the structural and kinetic response of small intestinal crypt epithelial cells including stem cells to highly active antiretroviral therapy (HAART). Design Crypt size and proliferative activity of transit and stem cells in jejunal mucosa were quantified using morphometric techniques. Methods Crypt length was measured by counting the number of enterocytes along one side of a number of crypts in each biopsy specimen and the mean crypt length was calculated. Proliferating crypt cells were identified with MIB-1 monoclonal antibody, and the percentage of crypt cells in proliferation was calculated at each cell position along the length of the crypt (proliferation index). Data were obtained from 9 HIV-positive test patients co-infected with microsporidia, 34 HIV-positive patients receiving HAART and 13 control cases. Results Crypt length was significantly greater in test patients than in controls, but crypt length in patients receiving HAART was normal. The proliferation index was greater in test subjects than in controls in stem and transit cell compartments, and was decreased in patients treated with HAART only in the stem cell region of the crypt. Conclusions Villous atrophy in HIV enteropathy is attributed to crypt hypertrophy and encroachment of crypt cells onto villi. HAART restores normal crypt structure by inhibition of HIV-driven stem cell hyperproliferation at the crypt bases.

Even though new drugs have been approved for treatment of hepatitis C virus (HCV) infection, the risk of drug-drug interactions and concern about overlapping toxicities has hindered the development of studies in HIV/HCV-coinfected individuals. Traditional treatment with pegylated interferon plus ribavirin (peg-IFN + RBV) is very expensive and has a low rate of sustained virological response in coinfected patients, especially if they are infected with HCV genotype 1. Nitazoxanide (NTZ) is a drug that is being evaluated for the treatment of chronic HCV infection, both in HCV-monoinfected and HIV/HCV-coinfected patients. Understanding the NTZ resistance mechanism could allow the development of resistance to be minimized and would expand the treatment options, mainly in special populations such as HIV/HCV-coinfected patients. Similarly to IFN, NTZ increases the activity of the cellular protein kinase activated by double-stranded RNA (PKR), a key kinase in the innate antiviral response. In order to elucidate whether sequence heterogeneity in the PKR-binding domain of HCV NS5A genotype 1 could influence the antiviral activity of either NTZ monotherapy or peg-IFN + RBV, baseline and end-of-therapy plasma samples from two groups of eleven non-responder HIV/HCV-coinfected patients that had received NTZ or peg-IFN + RBV were studied. Most of the HCV NS5A sequences examined at the end of therapy did not change from the baseline, even after 30 days course of antiviral therapy. An extensive comparison of HCV NS5A genotype 1 and 4 sequences from the database with reported IFN therapy outcome was performed in order to infer their phylogenetic relationships. The HCV genotype 1 NS5A nucleotide sequences from therapy-non-responder patients were intermingled amongst those from the database, irrespective of their IFN-therapy outcome. When comparing NS5A-PKRBD amino acid sequences, significant differences were observed in genotype 4, but not in genotype 1 (p 0.0001 and p 0.05, respectively). In conclusion, despite IFN and NTZ sharing the protein kinase activated by double-stranded RNA as their cellular target, the HCV genotype 1 strategy to counteract the IFN action mediated by NS5A ISDR/PKRBD does not explain drug resistance in HIV/HCV-coinfected patients. Other viral factors that are possibly involved are discussed as well.

Background ODIN (once-daily darunavir in treatment-experienced patients) was a 48-week, phase III, randomized, open-label trial comparing once-daily (qd) darunavir/ritonavir (DRV/r) 800/100 mg with twice-daily (bid) DRV/r 600/100 mg, both with an optimized background regimen [OBR; at least two nucleoside reverse transcriptase inhibitors (NRTIs)], in treatment-experienced, HIV-1-infected adults with no DRV resistance-associated mutations (RAMs) at screening. Week 48 analyses of virological response by subgroups are reported. Methods A total of 590 patients were randomized to receive qd (n = 294) or bid (n = 296) DRV/r. Virological response (HIV-1 RNA 50 000 copies/mL. Response rates for the qd and bid treatment arms by baseline CD4 cell count were also similar (69.6 vs. 65.2% for

Many HIV-infected patients fail to achieve undetectable viral load and are not retained in care. This pilot study examined patients lost to care in public and private clinics in Buenos Aires, Argentina. The impact of patient and provider interventions was compared separately and collectively. In Phase 1, participants prescribed antiretrovirals (ARVs) and non-adherent to treatment in the prior 3 to 6 months (n = 60) were randomized to patient intervention or standard of care (SOC) and assessed over 12 months. In Phase 2, providers were trained in interviewing techniques and 60 additional patients were randomized to patient intervention or SOC condition. Averaged across patient intervention status, Phase 2 provider intervention patients reported the most improved adherence and viral suppression at 6 and 12 months. Adherence in “patient intervention only” improved at midpoint and returned to baseline at 12 months. Results suggest provider training sustained patient adherence and viral suppression among “hard to reach” patients.

Challenging HIV-infected patients, those neither adherent nor actively engaged in care, represent an important opportunity for intervention if the HIV epidemic is to be contained. This pilot study assessed the feasibility and acceptability of an adapted patient adherence intervention and a motivational interviewing-based provider intervention in urban Buenos Aires, Argentina, in order to optimize health benefits in challenging HIV-infected patients. To maximize implementation and uptake of both strategies, interventions were adapted to the local setting. Qualitative data and a short quantitative assessment from patients, staff, fellows, residents and physicians (n = 84) were examined to establish the feasibility and acceptability of offering patient and provider evidence-based interventions in both public and private healthcare settings. Results identified key themes on provision of information, use of specialized communication techniques, and group support in the utilization of the interventions. Both providers (n = 12) and patients (n = 120) endorsed the acceptability and value of the interventions, and the feasibility of their delivery. Findings support the use of both intervention modalities with challenging patients in diverse urban healthcare settings.

Acquired immune deficiency syndrome has been one of the most devastating epidemics of the last century. The current estimate for people living with the HIV is 36.9 million. Today, despite availability of potent and safe drugs for effective treatment, lifelong therapy is required for preventing HIV re-emergence from a pool of latently infected cells. However, recent evidence show the importance to expand HIV testing, to offer antiretroviral treatment to all infected individuals, and to ensure retention through all the cascade of care. In addition, circumcision, pre-exposure prophylaxis, and other biomedical tools are now available for included in a comprehensive preventive package. Use of all the available tools might allow cutting the HIV transmission in 2030. In this article, we review the status of the epidemic, the latest advances in prevention and treatment, the concept of treatment as prevention and the challenges and opportunities for the HIV cure agenda.

Pasien gagal jantung kongestif (GJK) yang membutuhkan tindakan bedah sering timbul penyulit dengan prognosis yang buruk karena GJK dapat meningkatkan risiko mortalitas pasca-operasi. Penggunaan anestesi regional dengan blok epidural neuroaksial pada pasien GJK dengan memperhatikan efek blok simpatis dan risiko penurunan systemic vascular resistance atau risiko yang bisa terjadi dapat kita lakukan dengan menggunakan dosis rendah serta menjaga kecukupan volume intravaskular. Perempuan berumur 56 tahun yang terdiagnosis localized advance breast cancer kiri direncanakan modified radical mastectomy. Pasien juga menderita GJK fungsional klas III ec hipertensi kronis dan diabetes melitus dengan hipokinetik global. Penderita diberi premedikasi midazolam 1 mg, ketamin 20 mg dan fentanil 25 mcg kemudian dilakukan pemasangan alat monitoring, arteri line, kateter vena sentral, serta dilakukan anestesi epidural dengan kateter epidural di vertebra torakal IV-V menggunakan jarum touhy 18G dengan panjang kateter di ruang epidural 5 cm. Regimen anestesi epidural yang digunakan adalah levobupivacain 0,5% volume 8 mL. Operasi selama 2 jam 50 menit, posisi head up 45 derajat, hemodinamik selama operasi stabil dengan topangan norepinefrin 0,05-0,1 mcg/KgBB/menit dan dobutamin 5 mcg/KgBB/menit. Anestesi epidural merupakan tehnik anestesi yang dapat dilakukan pada pasien GJK dengan hipokinetik global, penurunan fungsi ventrikel kiri berat (fraksi ejeksi 32%) dan fungsional klas III Patient with congestive heart failure (CHF) that need surgery has a possibility of complication that can increase mortality rate after surgery. The use of regional anesthesia with neuroaxial epidural block in CHF patient is considered safe, decreases the risk of systemic vascular resistance, we can use low dose and maintain adequate intravascular volume. Female, 56 years old, with diagnose of left localized advance breast cancer, scheduled for modified radical mastectomy. She had CHF functional class III caused by chronic hypertension accompanied by diabetes mellitus and global hypokinetic. Midazolam 1 mg, ketamin 20 mg, and fentanyl 25 mcg was given as premedication patient, followed by inplace monitoring tools, insertion arterial line, and central venous catheter. Epidural catheter was placed between thoracal vertebrae IV and V, with epidural anesthesia regimen of levobupivacain 0.5% 8 mL. Duration of surgery was 2 hours and 50 minutes, with 45 degree head up position. The intraoperative hemodynamic parameters was stable and supported by norepinephrine 0.05-0.1 mcg/KgBW/minute and dobutamine 5 mcg/KgBW/minute. This case report proved that epidural anesthesia technique could be used for patient with CHF with global hypokinetic, severe decreased of left ventricle function (EF 32%) and functional class III.

New human polyomaviruses have been recently described. The aim of this work was to detect and characterize human polyomaviruses circulating in Argentina by recovering viruses from environmental and sewage samples and evaluating their potential role as viral indicators of human waste contamination. Analysis was performed in a wider context including viruses from clinical samples from an immunocompromised population. River water and sewage samples were analyzed as a strategy to study the molecular epidemiology of viruses excreted by millions of people. Samples belonged to the Matanza-Riachuelo River (2005-2006: n = 25 and 2012: n = 20) and sewage from Buenos Aires city and suburbs (2011 and 2013: n = 24). Viral detection was performed by PCR and the amplified viral genomes were characterized by phylogenetic analysis. Polyomaviruses were detected in 95.8% of sewage samples, identifying BKPyV (87.5%), JCPyV (83.3%), MCPyV (8.3%) and HPyV6 (8.3%). Besides, one sample collected in 2009 resulted positive for HPyV7. In 2005-2006, polyomaviruses were detected in 84.0% of river water samples, with the highest detection for MCPyV (52.0%), followed by BKPyV (44.0%), JCPyV (20.0%) and MWPyV (4.0%). In 2012, polyomaviruses were detected in 85.0% of river samples, finding JCPyV (85.0%), BKPyV (75.0%), MCPyV (25.0%) and HPyV6 (25.0%). Also, polyomaviruses, including JCPyV, BKPyV and MCPyV, were detected in 63.2% of urine samples from patients infected with HIV (n = 19). Characterization indicated the coexistence of different genotypes and variants for each virus, particularly in sewage. MCPyV sequences (the only sequences from Argentina) formed a monophyletic group with the single sequence available for South America (French Guiana). The high level of detection and viral diversity found by environmental surveillance, which involved the characterization of viruses not previously described in South America, reinforces the usefulness of this approach to monitor viral contamination and describe the viral epidemiology in the general population. Fil: Torres, Carolina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina Fil: Barrios, Melina Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina Fil: Cammarata, Robertina Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina Fil: Cisterna, Daniel Marcelo. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; Argentina Fil: Estrada, Tatiana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; Argentina Fil: Martini Novas, Sergio. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; Argentina Fil: Cahn, Pedro. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; Argentina Fil: Blanco Fernandez, Maria Dolores. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina Fil: Mbayed, Viviana Andrea. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina

Introduction : Maps are powerful tools for visualization of differences in health indicators by geographical region, but multi-country maps of HIV indicators do not exist, perhaps due to lack of consistent data across countries. Our objective was to create maps of four HIV indicators in North, Central, and South American countries. Methods : Using data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) and the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet), we mapped median CD4 at presentation for HIV clinical care, proportion retained in HIV primary care, proportion prescribed antiretroviral therapy (ART), and the proportion with suppressed plasma HIV viral load (VL) from 2010 to 2012 for North, Central, and South America. The 15 Canadian and US clinical cohorts and 7 clinical cohorts in Argentina, Brazil, Chile, Haiti, Honduras, Mexico, and Peru represented approximately 2–7% of persons known to be living with HIV in these countries. Results : Study populations were selected for each indicator: median CD4 at presentation for care was estimated among 14,811 adults; retention was estimated among 87,979 adults; ART use was estimated among 84,757 adults; and suppressed VL was estimated among 51,118 adults. Only three US states and the District of Columbia had a median CD4 at presentation >350 cells/mm 3 . Haiti, Mexico, and several states had >85% retention in care; lower (50–74%) retention in care was observed in the US West, South, and Mid-Atlantic, and in Argentina, Brazil, and Peru. ART use was highest (90%) in Mexico. The percentages of patients with suppressed VL in the US South and Northeast were lower than in most of Central and South America. Conclusions : These maps provide visualization of gaps in the quality of HIV care and allow for comparison between and within countries as well as monitoring policy and programme goals within geographical boundaries. Keywords: Map; HIV indicators; CD4 T-lymphocyte count; retention in care; antiretroviral therapy; HIV RNA suppression; North America; Central America; South America; implementation science. To access the supplementary material to this article please see Supplementary Files in the column to the right (under Article Tools). (Published: 4 April 2016) Citation: Althoff KN et al. Journal of the International AIDS Society 2016, 19 :20707 http://www.jiasociety.org/index.php/jias/article/view/20707 | http://dx.doi.org/10.7448/IAS.19.1.20707

Introduction : We assessed trends in HIV Care Continuum outcomes associated with delayed disease progression and reduced transmission within a large Latin American cohort over a decade: clinical retention, combination antiretroviral therapy (cART) use and viral suppression (VS). Methods : Adults from Caribbean, Central and South America network for HIV epidemiology clinical cohorts in seven countries contributed data between 2003 and 2012. Retention was defined as two or more HIV care visits annually, >90 days apart. cART was defined as prescription of three or more antiretroviral agents annually. VS was defined as HIV-1 RNA

Rilpivirine (RPV) is a once-daily (qd) non-nucleoside reverse transcriptase inhibitor that was evaluated in antiretroviral treatment-naive, HIV-1-infected adults (with two nucleotide reverse transcriptase inhibitors) in two international, double-blind, double-dummy, Phase III trials (ECHO and THRIVE). Both trials met their primary objective of demonstrating noninferior efficacy of RPV 25-mg qd versus efavirenz 600-mg qd regarding the proportion of patients with a confirmed response (viral load

Recientemente se ha observado un aumento en la prevalencia de Staphylococcus aureus resistente a la meticilina (SAMR) en pacientes ambulatorios con infecciones de piel y partes blandas (IPyPB). Los datos epidemiológicos locales disponibles son limitados. Se realizó un estudio descriptivo, prospectivo, de consultantes con IPyPB en la División Infectología del Hospital General de Agudos Juan A. Fernández, en el período 01/10/2009 a 31/01/2011. Fueron 130; edad mediana 36 años (RIC 25.9-43.5); hombres 61.5%. El 46.9% era HIV+. Cien cultivos (76.9%), de 100 pacientes, resultaron positivos: 83 S. aureus, 8 Streptococcus spp. y 9 con otros microorganismos. De los S. aureus aislados, 62 (74.7%) fueron resistentes a oxacilina, 12 (14.4%) a clindamicina, 14 (16.9%) a eritromicina, 5 (6%) a ciprofloxacina, presentando en algunos casos más de una resistencia. Todos fueron sensibles a rifampicina y minociclina, y 98.8% (82) a trimetoprima-sulfametoxazol. El 83.8% (52) de los pacientes con SAMR tenían algún factor de riesgo (FR), sin diferencias con los pacientes con otros aislamientos. La presentación clínica más frecuente de IPyPB / SAMR fue forunculosis: 56.4 (35/62) vs. 28.9% (11/38) en infecciones por otros microorganismos (p = 0.013). La resistencia a oxacilina fue similar entre pacientes HIV+ y negativos (79.1 vs. 70%, p = 0.179) (34/43 vs. 28/40). Concluimos que en la población estudiada se encontró una alta prevalencia de SAMR, independientemente de la serología para HIV o la presencia de FR. Las opciones de tratamiento empírico para este microorganismo son minociclina y trimetoprima-sulfametoxazol.

Adherence to antiretrovirals by pregnant women (and postpartum women if breastfeeding) is crucial to effectively decrease maternal viral load and decrease the risk of mother-to-child transmission of HIV. Our objectives were to describe self-reported adherence to antiretrovirals during the antepartum (after 22 weeks of pregnancy) and postpartum periods (6–12 weeks and 6 months), and identify predictors of adherence among HIV-infected women enrolled and followed in a prospective cohort study from June 2008 to June 2010 at multiple sites in Latin America. Adherence was evaluated using the number of missed and expected doses during the 3 days before the study visit. At the pre-delivery visit, 340 of 376 women (90%) reported perfect adherence. This rate significantly decreased by 6–12 weeks (171/214 [80%]) and 6 months postpartum (163/199 [82%], p

Summary Background Efavirenz with tenofovir-disoproxil-fumarate and emtricitabine is a preferred antiretroviral regimen for treatment-naive patients infected with HIV-1. Rilpivirine, a new non-nucleoside reverse transcriptase inhibitor, has shown similar antiviral efficacy to efavirenz in a phase 2b trial with two nucleoside/nucleotide reverse transcriptase inhibitors. We aimed to assess the efficacy, safety, and tolerability of rilpivirine versus efavirenz, each combined with tenofovir-disoproxil-fumarate and emtricitabine. Methods We did a phase 3, randomised, double-blind, double-dummy, active-controlled trial, in patients infected with HIV-1 who were treatment-naive. The patients were aged 18 years or older with a plasma viral load at screening of 5000 copies per mL or greater, and viral sensitivity to all study drugs. Our trial was done at 112 sites across 21 countries. Patients were randomly assigned by a computer-generated interactive web response system to receive either once-daily 25 mg rilpivirine or once-daily 600 mg efavirenz, each with tenofovir-disoproxil-fumarate and emtricitabine. Our primary objective was to show non-inferiority (12% margin) of rilpivirine to efavirenz in terms of the percentage of patients with confirmed response (viral load Findings 346 patients were randomly assigned to receive rilpivirine and 344 to receive efavirenz and received at least one dose of study drug, with 287 (83%) and 285 (83%) in the respective groups having a confirmed response at week 48. The point estimate from a logistic regression model for the percentage difference in response was −0·4 (95% CI −5·9 to 5·2), confirming non-inferiority with a 12% margin (primary endpoint). The incidence of virological failures was 13% (rilpivirine) versus 6% (efavirenz; 11% vs 4% by ITT-TLOVR). Grade 2–4 adverse events (55 [16%] on rilpivirine vs 108 [31%] on efavirenz, p vs 27 [8%] on efavirenz), rash, dizziness, and abnormal dreams or nightmares were more common with efavirenz. Increases in plasma lipids were significantly lower with rilpivirine. Interpretation Rilpivirine showed non-inferior efficacy compared with efavirenz, with a higher virological-failure rate, but a more favourable safety and tolerability profile. Funding Tibotec.

En la Argentina, el diagnóstico del HIV se realiza por solicitud voluntaria de los individuos o a través de la detección de sintomatología asociada a la infección. Sin embargo, debido a la elevada proporción de sujetos portadores que desconocen su estado serológico son necesarias nuevas estrategias. En el presente artículo mostramos cómo un modelo matemático predice el impacto de la expansión de la prueba diagnóstica del HIV en la Argentina. El modelo se basa en matrices de Markov y utiliza probabilidades de transición dependientes de parámetros obtenidos de estudios de cohortes nacionales e internacionales. Las predicciones incluyen tiempo en estadios clínicos y tratamiento, conteo de CD4, carga viral, estadío de infección, edad, tasas de mortalidad y proporción de infección desconocida a nivel poblacional. Las simulaciones se desarrollaron para la situación actual y para un escenario hipotético con diagnóstico más temprano. Mostramos predicciones que sugieren que el diagnóstico realizado antes de la progresión a sida incrementaría la expectativa de vida en unos 10.7 años. También, mostramos cómo la reducción del tiempo al diagnóstico hasta 5 años o menos desde la infección reduciría la tasa de mortalidad en el primer año de HAART de 7.6% a 2.1%, la proporción de infección no reconocida de 43.2% a 23.8% y la proporción de individuos con infección desconocida y que requieren tratamiento de 12% a 0.2%. Basados en estas predicciones resaltamos la importancia de implementar políticas de salud destinadas a detectar la infección por HIV en estadios tempranos en la Argentina.

Aims: The impact of baseline characteristics on response to the non-nucleoside reverse transcriptase inhibitor etravirine was investigated at 48 weeks in the Phase III DUET trials. Methods: Logistic regression was used to examine the effect of baseline demographics, disease characteristics and characteristics of antiretroviral therapy on virologic response (viral load

Context Recent data regarding the consequences of untreated human immunodeficiency virus (HIV) infection and the expansion of treatment choices for antiretroviral-naive and antiretroviral-experienced patients warrant an update of the International AIDS Society-USA guidelines for the use of antiretroviral therapy in adults with HIV infection. Objectives To provide updated recommendations for management of HIV-infected adults, using antiretroviral drugs and laboratory monitoring tools available in the international, developed-world setting. This report provides guidelines for when to initiate antiretroviral therapy, selection of appropriate initial regimens, patient monitoring, when to change therapy, and what regimens to use when changing. Data Sources and Study Selection A panel with expertise in HIV research and clinical care reviewed relevant data published or presented at selected scientific conferences since the last panel report through April 2010. Data were identified through a PubMed search, review of scientific conference abstracts, and requests to antiretroviral drug manufacturers for updated clinical trials and adverse event data. Data Extraction and Synthesis New evidence was reviewed by the panel. Recommendations were drafted by section writing committees and reviewed and edited by the entire panel. The quality and strength of the evidence were rated and recommendations were made by full panel consensus. Conclusions Patient readiness for treatment should be confirmed before initiation of antiretroviral treatment. Therapy is recommended for asymptomatic patients with a CD4 cell count 500/mu L. Components of the initial and subsequent regimens must be individualized, particularly in the context of concurrent conditions. Patients receiving antiretroviral treatment should be monitored regularly; treatment failure should be detected and managed early, with the goal of therapy, even in heavily pretreated patients, being HIV-1 RNA suppression below commercially available assay quantification limits. JAMA. 2010;304(3):321-333 www.jama.com

Apricitabine is a novel deoxycytidine nucleoside reverse transcriptase inhibitor (NRTI) currently in clinical development for the treatment of HIV infection. Apricitabine shows antiviral activity in vitro against HIV-1 strains and clinical isolates with mutations in the reverse transcriptase that confer resistance to other NRTIs, including M184V, thymidine analogue mutations (TAMs), nucleoside-associated mutations such as L74V and certain mutations at codon 69. Apricitabine has shown activity in treatment-experienced HIV-1-infected patients with NRTI resistance (with M184V and up to five TAMs) as well as in treatment-naive patients. Resistance to apricitabine is slow to develop in vitro and there has been little evidence of development of resistance to apricitabine in clinical use thus far, including patients receiving apricitabine for up to 48 weeks. The resistance profile of apricitabine suggests there is a low potential for cross-resistance with the currently available NRTIs and, thus, apricitabine may provide a treatment option for treatment-experienced HIV-1-infected patients with resistance to other NRTIs. In particular, the activity of apricitabine in the presence of the M184V mutation, which confers high-level resistance to lamivudine and emtricitabine, lends it to being used as a replacement for deoxycytidine analogues in patients who have failed treatment with lamivudine or emtricitabine.

OBJECTIVES Thymidine-based nucleoside analogue reverse transcriptase inhibitors and some protease inhibitors of HIV are associated with lipoatrophy, relative central fat accumulation and insulin resistance. The latter associations have not been well evaluated prospectively in adults commencing antiretroviral therapy. We studied the effects of protease inhibitor-based antiretroviral regimens on body composition, insulin sensitivity and adipocytokine levels. DESIGN 48-week substudy of a randomized, open-label, three-arm trial. SETTING Hospital and community HIV clinics. PARTICIPANTS 140 HIV-infected adults naive to antiretroviral therapy. INTERVENTION Tipranavir/ritonavir [500/200 mg twice a day (TPV/r200)] or [500/100 mg twice a day (TPV/r100)] or lopinavir/ritonavir [400/100 mg twice a day (LPV/r)], each with tenofovir + lamivudine. MAIN OUTCOME MEASURES Body composition [dual-energy x-ray absorptiometry for limb fat; L4, abdominal computed tomography for visceral adipose tissue (VAT)]; and fasting metabolic parameters. The primary analysis was change in limb fat mass in each TPV/r group vs. LPV/r. RESULTS Limb fat increased in all three groups: LPV/r (1.17 kg) versus TPV/r200 (0.83 kg; P = 0.16) and TPV/r100 (0.41 kg; P = 0.07). VAT decreased in all groups: LPV/r (-3 cm) vs. TPV/r200 (-9 cm; P = 0.04) and TPV/r100 (-6 cm; P = 0.40). No significant change in insulin sensitivity was observed, including by oral glucose tolerance testing. The increase in leptin levels was significantly correlated with the increase in limb fat mass (r = 0.67; P < 0.0001). Despite increased limb fat, adiponectin levels increased, but significantly more with TPV/r200 (+6010 ng/ml; P < 0.0001) or TPV/r100 (+4497 ng/ml; P = 0.002) when compared with LPV/r (+1360 ng/ml). CONCLUSION Unlike many other antiretroviral regimens, TPV/r or LPV/r with tenofovir-lamivudine increased subcutaneous fat without evidence for increasing visceral fat or insulin resistance over 48 weeks.

Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) as described for women with an established infection is, in most cases, associated with the transmission of few maternal variants. This study analysed virus variability in four cases of maternal primary infection occurring during pregnancy and/or breastfeeding. Estimated time of seroconversion was at 4 months of pregnancy for one woman (early seroconversion) and during the last months of pregnancy and/or breastfeeding for the remaining three (late seroconversion). The C2V3 envelope region was analysed in samples of mother–child pairs by molecular cloning and sequencing. Comparisons of nucleotide and amino acid sequences as well as phylogenetic analysis were performed. The results showed low variability in the virus population of both mother and child. Maximum-likelihood analysis showed that, in the early pregnancy seroconversion case, a minor viral variant with further evolution in the child was transmitted, which could indicate a selection event in MTCT or a stochastic event, whereas in the late seroconversion cases, the mother's and child's sequences were intermingled, which is compatible with the transmission of multiple viral variants from the mother's major population. These results could be explained by the less pronounced selective pressure exerted by the immune system in the early stages of the mother's infection, which could play a role in MTCT of HIV-1.

PURPOSE OF REVIEW: There is growing recognition that greater investment in research is needed to expand our knowledge and understanding of how to scale up HIV programmes effectively and equitably in the context of weak health systems. Current debates acknowledge that there remains a gap in evidence on how HIV resources can best be managed to contribute to building health system capacity; how to integrate HIV interventions into primary healthcare systems; and how HIV scale-up is affecting other disease programmes. RECENT FINDINGS: Findings suggest that global health initiatives, including HIV/AIDS programmes, should allocate a set portion of funding for research and knowledge generation in improving health system performance. Forms of HIV research with potential for building health system capacity in developing countries include clinical research, implementation and operations research, quality improvement research, economic evaluation and cost-effectiveness, HIV surveillance and population-based surveys, and monitoring and evaluation. SUMMARY: In this review, we present an overview of the imperative for HIV research in building health system capacity, provide examples of current trends and the forms of research with potential for enhancing health system performance, and highlight priorities for enhancing the role of HIV research in building health system capacity.

In the developed world, access to highly active antiretroviral therapy has led to a significant reduction in morbidity and mortality attributed to HIV/AIDS. However, the continual emergence of resistant HIV-1 strains and the limitations of currently available classes of antiretrovirals in terms of tolerance or toxicity highlight the need to develop agents with novel mechanisms of action. Successful completion of the HIV-1 viral life cycle requires the integration of cDNA mediated by the enzyme HIV-1 integrase, one of three essential enzymes encoded in the viral genome. Raltegravir, the first integrase inhibitor, acts specifically to block the strand transfer step. In clinical trials, raltegravir has been shown to be a potent drug with a good pharmacokinetic and side-effect profile, both in treatment-naive and -experienced patients, and has achieved high rates of virological suppression even in those with limited treatment options. Raltegravir was approved by the US FDA in October 2007 and by the European Commission in December 2007 to be used in combination therapy in previously treated HIV-1-infected individuals.

The molecular pattern of the human immunodeficiency virus (HIV) epidemic in Argentina provides an appropriate scenario to study cellular immune responses in patients with non-clade B infection. We aimed to map T-cell responses in patients infected with BF recombinant variants and compare them with those of clade B patients. Sixteen recently infected patients were enrolled and grouped by viral subtype. Nef-specific responses were evaluated with a peptide matrix-based gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay using B and BF overlapping peptides. Cross-clade and clade-specific responses were found. A correlation between B versus BF Nef-specific responses was identified. Detailed analysis at the single-peptide level revealed that BF patients show a narrower response but greater magnitude. Nef immunodominant responses agreed with previous publications, although the B loop was targeted at an unexpectedly high frequency. The putative HLA allele(s) restricting each positive response was determined. Single-peptide level screening with two different peptide sets uncovered discordant responses (mostly caused by peptide offsetting) and allowed detection of increased breadth. Positive responses identified by ELISPOT assay were further studied by intracellular cytokine staining. These were almost exclusively mediated by CD8 T cells. Characterization of concordant responses revealed that cells show distinct functional profiles, depending on the peptide presented. Last, quality (in terms of polyfunctionality) of T cells was associated with better viral replication containment. Overall, interclade differences in the frequency of epitopes recognized, structural domains targeted, and magnitude of responses were identified. Screening T-cell responses with multiple sets increased sensitivity. Further support for the notion of polyfunctional CD8+T-cell requirement to better control viral replication is also provided.

Shortages of health-care staff are endemic in sub-Saharan Africa (table). Overall, there is one physician for every 8000 people in the region. In the worst affected countries, such as Malawi, the physician-to-population ratio is just 0·02 for every 1000 (one per 50 000). There are also huge disparities between rural and urban areas: rural parts of South Africa have 14 times fewer doctors than the national average. These numbers are very different to those in developed countries: the UK, for example, has over 100 times more physicians per population than Malawi. Furthermore, almost one in ten doctors working in the UK are from Africa. The insufficiency of health staff to provide even basic services is one of the most pressing impediments to health-care delivery in resource-poor settings. The consequences are clearly shown by the inverse relation that exists between health-care worker density and mortality.

Context: The availability of new antiretroviral drugs and formulations, including drugs in new classes, and recent data on treatment choices for antiretroviral-naive and -experienced patients warrant an update of the International AIDS Society–USA guidelines for the use of antiretroviral therapy in adult human immunodeficiency virus (HIV) infection. Objectives: To summarize new data in the field and to provide current recommendations for the antiretroviral management and laboratory monitoring of HIV infection. This report provides guidelines in key areas of antiretroviral management: when to initiate therapy, choice of initial regimens, patient monitoring, when to change therapy, and how best to approach treatment options, including optimal use of recently approved drugs (maraviroc, raltegravir, and etravirine) in treatment-experienced patients. Data Sources and Study Selection: A 14-member panel with expertise in HIV research and clinical care was appointed. Data published or presented at selected scientific conferences since the last panel report (August 2006) through June 2008 were identified. Data Extraction and Synthesis: Data that changed the previous guidelines were reviewed by the panel (according to section). Guidelines were drafted by section writing committees and were then reviewed and edited by the entire panel. Recommendations were made by panel consensus. Conclusions: New data and considerations support initiating therapy before CD4 cell count declines to less than 350/μL. In patients with 350 CD4 cells/μL or more, the decision to begin therapy should be individualized based on the presence of comorbidities, risk factors for progression to AIDS and non-AIDS diseases, and patient readiness for treatment. In addition to the prior recommendation that a high plasma viral load (eg, 100 000 copies/mL) and rapidly declining CD4 cell count ( 100/μL per year) should prompt treatment initiation, active hepatitis B or C virus coinfection, cardiovascular disease risk, and HIV-associated nephropathy increasingly prompt earlier therapy. The initial regimen must be individualized, particularly in the presence of comorbid conditions, but usually will include efavirenz or a ritonavir-boosted protease inhibitor plus 2 nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine). Treatment failure should be identified and managed promptly, with the goal of therapy, even in heavily pretreated patients, being an HIV-1 RNA level below assay detection limits.

Introduction Emergence of nevirapine (NVP) resistance may be a consequence of its use in monotherapy to prevent HIV mother-to-child transmission (MTCT). The aim of this study was to evaluate the emergence of strains resistant to NVP and lamivudine (3TC) after discontinuation of anti-retroviral therapy (ART) with 3TC/zidovudine (ZDV)/NVP. Methods Twenty pregnant women (ART-naive or pre-exposed only to ZDV), to whom 3TC/ZDV/NVP was prescribed as MTCT prophylaxis, were studied. They received ART for a median of 4 months with median viral load (VL) at labour Results No mutations associated with resistance to 3TC or NVP were found by standard population sequencing. Analysis of K103N by SPCR showed that 35% of the patients contained ≤0.1% of viruses carrying either the AAC or AAT mutations. For Y181C mutation, 10% of the patients contained Conclusions NVP associated with ZDV/3TC as a regimen to prevent MTCT may involve a low risk for the selection of antiretroviral-resistant strains and may not jeopardize the use of these same drugs for future treatment.

The HIV/AIDS epidemic has evolved in its third decade to be an unprecedented human catastrophe of global scale and importance. Although an historic response for change and intervention has led to decreased rates of new infections and HIV-associated mortality in many communities the enormity of the pandemic continues to overwhelm already constrained resources everywhere. Improved understanding of antiretroviral therapy (ART) responses and viral and host characteristics both within and between diverse settings and populations is needed to guide initiatives in HIV prevention and treatment worldwide. The merging of existing clinical and research data related to HIV infection and its associated disorders answers questions that currently cannot be addressed using randomized trials or single sources of data. Cohorts such as MACS WIHS HIVRN EuroSida and the Swiss HIV Cohort have produced important observations regarding the epidemiology and long-term outcomes of HIV-infected individuals residing in North America and Europe both before and after the era of highly active antiretroviral therapy (HAART). Assessments of short-term response to HAART in recently expanded single-site programmes have been reported globally. Collaborations such as TAHOD and ART-LINC have allowed short-term evaluation of antiretroviral programmes in resource-limited settings from several continents and recently comparisons of outcomes in the first year of ART between low- and high-income countries have been reported. (excerpt)

The objective was to describe the management of a population of human immunodeficiency virus (HIV)-infected pregnant women in Latin America and the Caribbean and to assess factors associated with maternal viral load of 1000 copies/ mL or more and with infant HIV-1 infection. Eligibility criteria were enrollment in the prospective cohort study as of March 2006; delivery of a liveborn singleton infant; and completion of the 6-month postpartum or postnatal visit. Of 955 women enrolled in Argentina the Bahamas Brazil and Mexico 770 mother-infant pairs were eligible. At enrollment most women were relatively healthy (87% asymptomatic 59% with viral load less than 1000 copies/mL 62% with CD4+% of 25% or more). Most (99%) received antiretrovirals during pregnancy (56% prophylaxis 44% treatment) and 38% delivered by cesarean before labor and before ruptured membranes. Only 18% of women had a viral load of 1000 copies/mL or more after delivery (associated in adjusted analyses with receipt of antiretrovirals at conception CD4+% [lower] viral load [higher] and country at enrollment enrollment late in pregnancy and inversely related to antiretroviral regimen [two nucleoside or nucleotide analogue reverse transcriptase inhibitors plus one nonnucleoside reverse transcriptase inhibitor] during pregnancy). None of the infants breastfed and all received antiretroviral prophylaxis. Seven infants became infected (0.91%; 95% confidence interval 0.37-1.86). Low birth weight infants and those whose mothers had a low CD4+% at hospital discharge after delivery and were not receiving antiretrovirals at enrollment were at higher risk of HIV infection. Only a minority of women had a viral load of 1000 copies/mL or more around delivery and mother-to-child transmission of HIV occurred rarely (1%). (authors)

Existing nucleoside reverse transcriptase inhibitors for HIV disease are limited by problems of resistance and, in some cases, long-term toxicity. Apricitabine (ATC; formerly BCH10618, SPD754 and AVX754) is a deoxycytidine analogue nucleoside reverse transcriptase inhibitor in clinical development. ATC retains substantial in vitro activity against HIV-1 containing many mutations associated with nucleoside reverse transcriptase inhibitor resistance, showing a less than twofold reduction in susceptibility in the presence of either up to five thymidine analogue mutations or the M184V mutation. ATC showed a low potential for cellular or mitochondrial toxicity in vitro. ATC is well absorbed orally, with a bioavailability of 65–80%. Its plasma elimination half-life (approximately 3 h), and the intracellular half-life of its triphosphate (TP) metabolite (6–7 h) support twice-daily dosing. Intracellular ATC-TP levels are markedly reduced in the presence of lamivudine or emtricitabine, indicating that clinical co-administration of ATC together with these agents will not be possible. The drug is renally eliminated, giving a low potential for hepatic drug interactions. In a double-blind, randomized, placebo-controlled Phase II monotherapy trial in antiretroviral-naive patients, ATC doses of 1,200 and 1,600 mg/day reduced plasma viral load levels by 1.65 and 1.58 log10HIV RNA copies/ml, respectively, after 10 days of treatment ( P