Cabotegravir for HIV Prevention in Cisgender Men and Transgender Women.

BACKGROUND: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection. METHODS: We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection. RESULTS: The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified. CONCLUSIONS: CAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 083 ClinicalTrials.gov number, NCT02720094.).

A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia.

BACKGROUND: Convalescent plasma is frequently administered to patients with Covid-19 and has been reported, largely on the basis of observational data, to improve clinical outcomes. Minimal data are available from adequately powered randomized, controlled trials. METHODS: We randomly assigned hospitalized adult patients with severe Covid-19 pneumonia in a 2:1 ratio to receive convalescent plasma or placebo. The primary outcome was the patient's clinical status 30 days after the intervention, as measured on a six-point ordinal scale ranging from total recovery to death. RESULTS: A total of 228 patients were assigned to receive convalescent plasma and 105 to receive placebo. The median time from the onset of symptoms to enrollment in the trial was 8 days (interquartile range, 5 to 10), and hypoxemia was the most frequent severity criterion for enrollment. The infused convalescent plasma had a median titer of 1:3200 of total SARS-CoV-2 antibodies (interquartile range, 1:800 to 1:3200). No patients were lost to follow-up. At day 30 day, no significant difference was noted between the convalescent plasma group and the placebo group in the distribution of clinical outcomes according to the ordinal scale (odds ratio, 0.83; 95% confidence interval [CI], 0.52 to 1.35; P = 0.46). Overall mortality was 10.96% in the convalescent plasma group and 11.43% in the placebo group, for a risk difference of -0.46 percentage points (95% CI, -7.8 to 6.8). Total SARS-CoV-2 antibody titers tended to be higher in the convalescent plasma group at day 2 after the intervention. Adverse events and serious adverse events were similar in the two groups. CONCLUSIONS: No significant differences were observed in clinical status or overall mortality between patients treated with convalescent plasma and those who received placebo. (PlasmAr ClinicalTrials.gov number, NCT04383535.).

Telemedicine in HIV health care during the COVID-19 pandemic: An implementation research study in Buenos Aires, Argentina.

BACKGROUND: From October 2020 to October 2022, we conducted an implementation study to offer telemedicine (TM) across four HIV units of general public hospitals in Buenos Aires. The intervention used TM to provide a continuum of care to patients with HIV. METHODS AND SETTING: We used the RE-AIM framework to evaluate the strategy. The study started during a COVID-19 outbreak with strict lockdown policies and continued until return to normal practices. Implementation facilitation served as the core implementation strategy. RESULTS: We reached 4118 patients (58% of eligible individuals), and the main perceived benefits were the ability to avoid exposure to infectious diseases and reduced travel time and cost. After a median of 515 days of follow-up, 95.7% of participants with HIV were receiving antiretroviral therapy, and 87.8% were virally suppressed, with a median CD4+ count of 648 cells/µL. In total, 36.6% reported clinical events, and 20.4% presented with COVID-19 infection. The proportion of physicians adopting TM was 69.37%. After enrolment, 2406 of 5640 (43%) follow-up visits were conducted via TM. By the end of the study, 26.29% of appointments offered in the four centres were through TM, whereas 73.71% were in-person appointments. CONCLUSION: It was feasible to implement TM in the four centres in the public health sector in Buenos Aires, Argentina. It was acceptable for both patients and healthcare workers, and effectively reached a large proportion of the population served in these clinics. Both healthcare workers and patients consider it a model of care that will continue to be offered in the future.

Effect of Oral Oseltamivir on Virological Outcomes in Low-risk Adults With Influenza: A Randomized Clinical Trial.

BACKGROUND: Duration of viral shedding is a determinant of infectivity and transmissibility, but few data exist about oseltamivir's ability to alter viral shedding. METHODS: From January 2012 through October 2017, a randomized, double-blinded multicenter clinical trial was conducted in adults aged 18-64 years at 42 sites in Thailand, the United States, and Argentina. Participants with influenza A or B and without risk factors for complications of influenza were screened for the study. Eligible participants were randomized to receive oseltamivir 75 mg or placebo twice daily for 5 days. The primary endpoint was the percentage of participants with virus detectable by polymerase chain reaction in nasopharyngeal swab at day 3. RESULTS: Of 716 adults screened for the study, 558 were randomized, and 501 were confirmed to have influenza. Forty-six participants in the pilot study were excluded, and 449 of the 455 participants in the population for the primary analysis had day 3 viral shedding results. Ninety-nine (45.0%) of 220 participants in the oseltamivir arm had virus detected at day 3 compared with 131 (57.2%) of 229 participants in the placebo arm (absolute difference of -12.2% [-21.4%, -3.0%], P =; .010). The median time to alleviation of symptoms was 79.0 hours for the oseltamivir arm and 84.0 hours for the placebo arm (P =; .34) in those with confirmed influenza infection. CONCLUSIONS: Oseltamivir decreased viral shedding in this low-risk population. However, in the population enrolled in this study, it did not significantly decrease the time to resolution of clinical symptoms. CLINICAL TRIALS REGISTRATION: NCT01314911.

Association Between Single-Nucleotide Polymorphisms in HLA Alleles and Human Immunodeficiency Virus Type 1 Viral Load in Demographically Diverse, Antiretroviral Therapy-Naive Participants From the Strategic Timing of AntiRetroviral Treatment Trial.

The impact of variation in host genetics on replication of human immunodeficiency virus type 1 (HIV-1) in demographically diverse populations remains uncertain. In the current study, we performed a genome-wide screen for associations of single-nucleotide polymorphisms (SNPs) to viral load (VL) in antiretroviral therapy-naive participants (n = 2440) with varying demographics from the Strategic Timing of AntiRetroviral Treatment (START) trial. Associations were assessed using genotypic data generated by a customized SNP array, imputed HLA alleles, and multiple linear regression. Genome-wide significant associations between SNPs and VL were observed in the major histocompatibility complex class I region (MHC I), with effect sizes ranging between 0.14 and 0.39 log10 VL (copies/mL). Supporting the SNP findings, we identified several HLA alleles significantly associated with VL, extending prior observations that the (MHC I) is a major host determinant of HIV-1 control with shared genetic variants across diverse populations and underscoring the limitations of genome-wide association studies as being merely a screening tool.

Differences in response to antiretroviral therapy in HIV-positive patients being treated for tuberculosis in Eastern Europe, Western Europe and Latin America.

BACKGROUND: Efavirenz-based antiretroviral therapy (ART) regimens are preferred for treatment of adult HIV-positive patients co-infected with tuberculosis (HIV/TB). Few studies have compared outcomes among HIV/TB patients treated with efavirenz or non-efavirenz containing regimens. METHODS: HIV-positive patients aged ≥16 years with a diagnosis of tuberculosis recruited to the TB:HIV study between Jan 1, 2011, and Dec 31, 2013 in 19 countries in Eastern Europe (EE), Western Europe (WE), and Latin America (LA) who received ART concomitantly with TB treatment were included. Patients either received efavirenz-containing ART starting between 15 days prior to, during, or within 90 days after starting tuberculosis treatment, (efavirenz group), or other ART regimens (non-efavirenz group). Patients who started ART more than 90 days after initiation of TB treatment, or who experienced ART interruption of more than 15 days during TB treatment were excluded. We describe rates and factors associated with death, virological suppression, and loss to follow up at 12 months using univariate, multivariate Cox, and marginal structural models to compare the two groups of patients. RESULTS: Of 965 patients (647 receiving efavirenz-containing ART, and 318 a non-efavirenz regimen) 50% were from EE, 28% from WE, and 22% from LA. Among those not receiving efavirenz-containing ART, regimens mainly contained a ritonavir-boosted protease inhibitor (57%), or raltegravir (22%). At 12 months 1.4% of patients in WE had died, compared to 20% in EE: rates of virological suppression ranged from 21% in EE to 61% in WE. After adjusting for potential confounders, rates of death (adjusted Hazard Ratio; aHR, 95%CI: 1.13, 0.72-1.78), virological suppression (aHR, 95%CI: 0.97, 0.76-1.22), and loss to follow up (aHR, 95%CI: 1.17, 0.81-1.67), were similar in patients treated with efavirenz and non-efavirenz containing ART regimens. CONCLUSION: In this large, prospective cohort, the response to ART varied significantly across geographical regions, whereas the ART regimen (efavirenz or non-efavirenz containing) did not impact on the proportion of patients who were virologically-suppressed, lost to follow up or dead at 12 months.

Antiretroviral therapy and arterial elasticity in HIV-infected patients.

Cardiovascular risk is increased in HIV-infected patients and has become a leading cause of morbi-mortality in this population. The purpose of this study is to compare HIV-infected patients on antiretroviral therapy (ART) and ART-naïve HIV-infected patients regarding arterial elasticity. From September 2010 to September 2015, 105 HIV-infected subjects were enrolled, 41 ART-naïve and 64 on ART with stable viral suppression. Elasticity of large and small arteries (LAE and SAE) was assessed by analysis of radial pulse waveforms using a calibrated device. A single set of measurements was performed. Multivariate linear regression models were constructed to estimate independent correlates of arterial elasticity. On-ART and ART-naïve patients were similar with respect to gender, age, body mass index, Framingham cardiovascular risk score, smoking habits, and CD4+ counts. Median time on treatment was 60 months and 79% of patients were on regimens based on non-nucleoside reverse-transcriptase inhibitors. No significant differences in LAE and SAE assessments were found between groups. However, time on ART and cholesterol levels were independently associated with LAE impairment. No association between arterial elasticity and CD4+ counts was found. We conclude that cumulative exposure to ART may play a role on LAE impairment and deserves further investigation.

Late diagnosis of HIV infection in asymptomatic patients.

Recent findings from the START Trial provided evidence that early initiation of antiretroviral treatment should be implemented as the global standard of care. However, a large proportion of patients are still being diagnosed in late stages. Our objective was to evaluate the temporal trend in the CD4+ cell count at diagnosis during a 13 year period and the factors associated with late HIV diagnosis in asymptomatic individuals tested in the Centre for Prevention, Counselling and Diagnosis of our hospital. It was a retrospective study including all asymptomatic patients with new diagnosis of HIV infection. Very late presenters (VLP) were defined as those with CD4+ counts < 200 and late presenters (LP) with CD4+ < 350 cell/mm3. We also evaluated the proportion of patients diagnosed with CD4+ cell counts below 500 cell/mm3. Between January 2002 and December 2014, 20 263 patients were tested for HIV, 1104 with a positive result of whom 995 asymptomatic individuals were included. Overall, median CD4+ count was 372 cells/mm3 and HIV-RNA 31 145 copies/ml. There was no evidence that the CD4+ count at diagnosis progressively increased over time, nor that the proportion of VLP and LP decreased. In a multivariate model older age, heterosexual transmission and intravenous drug use remained as independent factors associated with LP. In conclusion, late diagnosis of HIV infection remains prevalent among asymptomatic patients, highlighting the need to continue implementing strategies towards early diagnosis.

Repeat pregnancy in women with HIV infection in Latin America and the Caribbean.

Intended and unintended pregnancies occur frequently among human immunodeficiency virus (HIV)-infected women. We evaluated the occurrence of repeat pregnancy and characteristics associated with this outcome among HIV-infected women in Latin America and the Caribbean who were participating in the National Institute of Child Health and Human Development (NICHD) International Site Development Initiative (NISDI). Of the 1342 HIV-infected pregnant women enrolled in NISDI, 124 (9.2%) had one or more repeat pregnancies on study. Median time between the index delivery and date of conception of the subsequent pregnancy was 1.4 years (range 0.1-5.7). Younger age (odds ratio [OR] = 1.07, 95% confidence interval [CI]: 1.04-1.11 per one year decrease in age), hospitalization during the index pregnancy or up to six months post-partum [OR = 2.0, 95% CI: 1.2-3.4], and poor index pregnancy outcome (stillbirth or spontaneous/therapeutic abortion; OR = 3.4, 95% CI: 1.4-8.4) were associated with increased occurrence of repeat pregnancy in multivariable analysis. Among women with repeat pregnancies, the proportion receiving antiretroviral treatment (vs. prophylaxis) increased from 39.4% at the time of the index pregnancy to 81.8% at the time of the repeat pregnancy (p < 0.001). These results can help identify women most likely to benefit from reproductive counseling in order to assist with healthy pregnancy planning and prevention of unintended pregnancies.

Short- and long-term mortality and causes of death in HIV/tuberculosis patients in Europe.

Mortality of HIV/tuberculosis (TB) patients in Eastern Europe is high. Little is known about their causes of death. This study aimed to assess and compare mortality rates and cause of death in HIV/TB patients across Eastern Europe and Western Europe and Argentina (WEA) in an international cohort study. Mortality rates and causes of death were analysed by time from TB diagnosis (<3 months, 3-12 months or >12 months) in 1078 consecutive HIV/TB patients. Factors associated with TB-related death were examined in multivariate Poisson regression analysis. 347 patients died during 2625 person-years of follow-up. Mortality in Eastern Europe was three- to ninefold higher than in WEA. TB was the main cause of death in Eastern Europe in 80%, 66% and 61% of patients who died <3 months, 3-12 months or >12 months after TB diagnosis, compared to 50%, 0% and 15% in the same time periods in WEA (p<0.0001). In multivariate analysis, follow-up in WEA (incidence rate ratio (IRR) 0.12, 95% CI 0.04-0.35), standard TB-treatment (IRR 0.45, 95% CI 0.20-0.99) and antiretroviral therapy (IRR 0.32, 95% CI 0.14-0.77) were associated with reduced risk of TB-related death. Persistently higher mortality rates were observed in HIV/TB patients in Eastern Europe, and TB was the dominant cause of death at any time during follow-up. This has important implications for HIV/TB programmes aiming to optimise the management of HIV/TB patients and limit TB-associated mortality in this region.

Quantifying how single dose Ad26.COV2.S vaccine efficacy depends on Spike sequence features.

In the ENSEMBLE randomized, placebo-controlled phase 3 trial (NCT04505722), estimated single-dose Ad26.COV2.S vaccine efficacy (VE) was 56% against moderate to severe-critical COVID-19. SARS-CoV-2 Spike sequences were determined from 484 vaccine and 1,067 placebo recipients who acquired COVID-19. In this set of prespecified analyses, we show that in Latin America, VE was significantly lower against Lambda vs. Reference and against Lambda vs. non-Lambda [family-wise error rate (FWER) p < 0.05]. VE differed by residue match vs. mismatch to the vaccine-insert at 16 amino acid positions (4 FWER p < 0.05; 12 q-value ≤ 0.20); significantly decreased with physicochemical-weighted Hamming distance to the vaccine-strain sequence for Spike, receptor-binding domain, N-terminal domain, and S1 (FWER p < 0.001); differed (FWER ≤ 0.05) by distance to the vaccine strain measured by 9 antibody-epitope escape scores and 4 NTD neutralization-impacting features; and decreased (p = 0.011) with neutralization resistance level to vaccinee sera. VE against severe-critical COVID-19 was stable across most sequence features but lower against the most distant viruses.

Does hepatitis C viremia or genotype predict the risk of mortality in individuals co-infected with HIV?

BACKGROUND & AIMS: The influence of HCV-RNA levels and genotype on HCV disease progression is not well studied. The prognostic value of these markers was investigated in HIV/HCV co-infected individuals from the EuroSIDA cohort. METHODS: EuroSIDA is a prospective cohort of 18,295 HIV-1 infected patients in 105 centres across Europe, Israel, and Argentina. All subjects with known HCV antibody (HCVAb) status (n=13,025) were enrolled in the present study. RESULTS: 4044 (31.0%) patients had detectable HCVAb. After adjustment, HCVAb+ patients had an increased incidence of liver-related death (LRD) compared to HCVAb- individuals (IRR 8.90; 95% CI 5.60-14.14, p<0.0001). Information on HCV-RNA was available for 2709 (67.0%) HCVAb+ patients and 2010 (74.2%) were HCV-RNA+. Of 1907 patients with measured HCV genotype, 1008 (52.9%), 62 (3.3%), 567 (29.7%), and 270 (14.2%) were infected with genotype 1, 2, 3 and 4, respectively. Patients with detectable HCV-RNA had similar incidence of non-LRD, but higher incidence of LRD compared to HCVAb+ aviremic patients (adjusted IRR 1.18; 95% CI 0.93-1.50, p=0.17) and (adjusted IRR 2.11; 95% CI 1.30-3.42, p=0.0025), respectively. In patients with HCV viremia, HCV-RNA levels and HCV genotype did not influence the risk of non-LRD or LRD. CONCLUSIONS: HCV seropositive HIV patients had a 9-fold increased risk of LRD compared to patients who were HCV seronegative. Risk of death from any cause or LRD was not influenced by level of HCV viremia or HCV genotype.

[Monkeypox: description of two cases under follow-up in Buenos Aires]. / Viruela símica: descripción de dos casos en seguimiento en Buenos Aires.

Monkeypox is an endemic disease in several African countries. In May 2022, an outbreak was reported in dozens of non-endemic countries. On July 23, 2022, the WHO Director-General declared this multinational outbreak a public health emergency of international concern. We report two cases of patients under follow-up in Buenos Aires, Argentina, between June and July 2022. Both were men who have sex with men, with the appearance of lesions in the genital area without a prodromal period. In both cases, treatment was carried out in the first instance with suspicion of sexually transmitted infections. We highlight the importance of considering this pathology as a differential diagnosis, taking into account the current epidemiological context.

La viruela símica es una enfermedad endémica en varios países de áfrica. En mayo de 2022 varios países donde la viruela símica no es endémica notificaron casos, incluyendo algunos países de las Américas. El 23 de julio de 2022, el Director General de la OMS declaró que este brote multinacional constituye una emergencia de salud pública de importancia internacional. Comunicamos dos casos de pacientes en seguimiento en la Ciudad de Buenos Aires, Argentina, entre junio y julio de 2022. Ambos eran hombres que tienen sexo con hombres, con aparición de lesiones en zona genital sin período prodrómico. En los dos casos se realizó tratamiento en primera instancia con sospecha de infecciones de transmisión sexual. Señalamos la importancia de considerar esta enfermedad como diagnóstico diferencial teniendo en cuenta el contexto epidemiológico actual.

Adaption of an ongoing clinical trial to quickly respond to gaps in changing international recommendations: the experience of D2EFT.

A rapidly changing landscape of antiretrovirals and their procurement at scale has permitted the evaluation of new optimised second-line antiretroviral therapy (ART) in low- and middle-income countries. D2EFT is an open-label randomised controlled non-inferiority phase IIIB/IV trial in people living with HIV-1 (PWH) whose first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART is failing. At inception, it compared a standard of care of boosted darunavir with two nucleos(t)ide reverse transcriptase inhibitors (NRTIs) to the novel NRTI-sparing regimen of boosted darunavir with dolutegravir. Implemented in 2017, participating sites were across Africa, Asia and Latin America. Around the time of implementation, the World Health Organization updated its treatment guidelines and recommended scaling up tenofovir disoproxil fumarate-lamivudine-dolutegravir (TLD). This situation pushed D2EFT investigators to consider the impact of the roll-out of TLD on the D2EFT research question. The protocol team agreed it was important to study TLD in second-line when an NNRTI regimen was failing, and focused on options to expedite the work by studying the question within the existing trial and network. All key issues (statistical, programmatic and financial) were reviewed to assess the benefits and risks of adding a third arm to the ongoing study, as opposed to developing a new randomised clinical trial with the same control arm and within the same network. The development of a new trial was deemed to be longer than adding a third arm, and to create a challenging situation with two competing clinical trials at the same sites which would slow down recruitment and impair both trials. On the other hand, adding a third arm would be demanding in terms of operationalisation, increased sample size and statistical biases to control. The optimal strategy was deemed to be the addition of a third arm, arriving retrospectively at a simplified multi-arm multi-stage clinical trial design to achieve statistical validity. The D2EFT study maintains additional value in a quickly evolving second-line ART strategy allowed by the progress in global access to ART.

Prevalence and outcomes of pregnancies in women with HIV over a 20-year period.

OBJECTIVE: To evaluate time trends in pregnancies and pregnancy outcomes among women with HIV in Europe. DESIGN: European multicentre prospective cohort study. METHODS: EuroSIDA has collected annual cross-sectional audits of pregnancies between 1996 and 2015. Pregnancy data were extracted and described. Odds of pregnancy were modelled, adjusting for potential confounders using logistic regression with generalized estimating equations. RESULTS: Of 5535 women aged 16 to <50 years, 4217 (76.2%) had pregnancy information available, and 912 (21.6%) reported 1315 pregnancies. The proportions with at least one pregnancy were 28.1% (321/1143) in East, 24.5% (146/596) in North, 19.8% (140/706) in West/Central, 19.3% (110/569) in Central East and 16.2% (195/1203) in South Europe. Overall 319 pregnancies (24.3%) occurred in 1996-2002, 576 (43.8%) in 2003-2009 and 420 (31.9%) in 2010-2015. After adjustment, the odds of pregnancy were lower in 1996-2002, in South, Central East and East compared to West/Central Europe, in older women, those with low CD4+ cell count or with prior AIDS, and higher in those with a previous pregnancy or who were hepatitis C virus positive.Outcomes were reported for 999 pregnancies in 1996-2014, with 690 live births (69.1%), seven stillbirths (0.7%), 103 spontaneous (10.3%) and 199 medical abortions (19.9%). CONCLUSIONS: Around 20% of women in EuroSIDA reported a pregnancy, with most pregnancies after 2002, when more effective antiretroviral therapy became available. Substantial differences were seen between European regions. Further surveillance of pregnancies and outcomes among women living with HIV is warranted to ensure equal access to care.

Hypersensitivity reactions, hepatotoxicity, and other discontinuations in persons receiving integrase strand transfer inhibitors: results from the EuroSIDA study.

Background: Hypersensitivity reaction (HSR) and hepatotoxicity are rare, but potentially serious side-effects of antiretroviral use.Objective: To investigate discontinuations due to HSR, hepatotoxicity or other reasons among users of dolutegravir (DTG) vs. raltegravir (RAL) or elvitegravir (EVG) in the EuroSIDA cohort.Methods: We compared individuals ≥18 years and starting combination antiretroviral therapy (ART, ≥3 drugs) with DTG vs. RAL or EVG, with or without abacavir (ABC), between January 16, 2014 and January 23, 2019. Discontinuations due to serious adverse events (SAEs) were independently reviewed.Results: Altogether 4366 individuals started 5116 ART regimens including DTG, RAL, or EVG, contributing 9180 person-years of follow-up (PYFU), with median follow-up 1.6 (interquartile range 0.7-2.8) years per treatment episode. Of these, 3074 (60.1%) used DTG (1738 with ABC, 1336 without) and 2042 (39.9%) RAL or EVG (286 with ABC, 1756 without). 1261 (24.6%) INSTI episodes were discontinued, 649 of the DTG-containing regimens (discontinuation rate 115, 95% CI 106-124/1000 PYFU) and 612 RAL or EVG-containing regimens (173, CI 160-188/1000 PYFU). After independent review, there were five HSR discontinuations, two for DTG (one with and one without ABC, discontinuation rate 0.35, CI 0.04-1.28/1000 PYFU), and three for RAL or EVG without ABC (0.85, CI 0.18-2.48/1000 PYFU). There was one hepatotoxicity discontinuation on DTG with ABC (discontinuation rate 0.18, CI 0.00-0.99/1000 PYFU).Conclusion: During 5 years of observations in the EuroSIDA cohort independently reviewed discontinuations due to HSR or hepatotoxicity were very rare, indicating a low rate of SAEs.

[Sexually transmitted infections among transgender individuals and other sexual identities]. / Infecciones de transmisión sexual en personas transgénero y otras identidades sexuales.

Few data are available regarding the prevalence of sexually transmitted infections (STI), including HIV-1 infection, and risk behaviors of transgender individuals. Previous reports indicate that this community has a high prevalence of HIV and STIs. Our objective was to compare the prevalence of HIV-1 infection, STI and risk behaviors of transgender people versus non transgender people. We used a cross sectional design study. Patients who received services at our testing site between November 2002 and April 2006, and provided written informed consent, were included in the analysis. Socio-demographic data, sexual behaviour, recreational drug use, condom use, concurrent or previous STI and HIV-1 infection diagnosis and partner serologic status, were collected. We used descriptive statistics and chi 2 for comparisons of proportions. In the period of the study, 105 transgender individuals were identified in a population of 4118 patients tested. The prevalence of HIV infection in the transgender group was 27.6% (29/105), while in the non transgender group was 6.2% (247/4013) p:0.0000. Low level of formal instruction, alcohol consumption, drug abuse, previous history of STI and sex work (100% transgenders and 2.3% of non-transgenders) were significantly more frequent in the transgender. The referred correct use of condom was similar in both groups. The prevalence of syphilis was 42.3% in transgender group and 18.1% in non-transgender individuals. These data show that this population has a very high prevalence of HIV-1 and STI. This information could be instrumental to design targets for intensive HIV prevention strategies in this particular high risk population.

Dolutegravir versus ritonavir-boosted lopinavir both with dual nucleoside reverse transcriptase inhibitor therapy in adults with HIV-1 infection in whom first-line therapy has failed (DAWNING): an open-label, non-inferiority, phase 3b trial.

BACKGROUND: Doubts exist regarding optimal second-line treatment options for HIV-1-infected patients in resource-limited settings. We assessed safety and efficacy of dolutegravir compared with ritonavir-boosted lopinavir, plus two nucleoside reverse transcriptase inhibitors (NRTIs) in adults in whom previous first-line antiretroviral therapy with a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two NRTIs has failed. METHODS: DAWNING is a phase 3b, open-label, parallel-group, non-inferiority, active-controlled trial done at 58 sites in 13 countries. Eligible adults were aged at least 18 years and, during at least 6 months of treatment with a first-line treatment containing an NNRTI and two NRTIs, had virological failure (confirmed HIV-1 RNA ≥400 copies per mL). Participants were randomly assigned by a central randomisation system to receive oral dolutegravir (50 mg once daily) or ritonavir-boosted lopinavir (800 mg lopinavir plus 200 mg ritonavir once daily or 400 mg plus 100 mg twice daily), plus two investigator-selected NRTIs (at least one fully active based on resistance testing at screening). The primary outcome was the proportion of participants achieving viral suppression (defined as plasma HIV-1 RNA <50 copies per mL) at week 48 using the snapshot algorithm and a non-inferiority margin of -12%. The primary analysis was done in an intention-to-treat-exposed (ITT-E) population of participants who received at least one dose of study medication, according to original group assignment. Safety was analysed in all participants who received at least one dose of study drug, according to which drug was received. The study was registered at ClinicalTrials.gov, number NCT02227238, and viiv-studyregister.com, number 200304. FINDINGS: Between Dec 11, 2014, and June 27, 2016, 968 adults were screened and 627 were randomly assigned to the dolutegravir group (n=312) or the ritonavir-boosted lopinavir group (n=315). Three patients in the ritonavir-boosted lopinavir group did not receive study medication and so 624 were included in the ITT-E population. At week 48, 261 (84%) of 312 participants in the dolutegravir group achieved viral suppression compared with 219 (70%) of 312 in the ritonavir-boosted lopinavir group (adjusted difference 13·8%; 95% CI 7·3-20·3). Non-inferiority was achieved on the basis of the 95% CI of the adjusted treatment difference having a lower bound greater than -12% (prespecified non-inferiority margin). Because the lower bound of the 95% CI is greater than zero (7·3%), superiority of dolutegravir was also concluded (p<0·0001). The safety profile for dolutegravir was favourable compared with that of ritonavir-boosted lopinavir. More grade 2-4 drug-related adverse events occurred with ritonavir-boosted lopinavir than dolutegravir (44 [14%] of 310 with ritonavir-boosted lopinavir vs 11 [4%] of 314 with dolutegravir), mainly driven by gastrointestinal disorders. INTERPRETATION: When administered with two NRTIs, dolutegravir was superior to ritonavir-boosted lopinavir at 48 weeks and can be considered a suitable option for second-line treatment. FUNDING: ViiV Healthcare.

Drug resistance among HIV-infected pregnant women receiving antiretrovirals for prophylaxis.

OBJECTIVE: To quantify primary resistance mutations (PRMs) among HIV-1-infected women receiving antiretroviral therapy (ART) for prevention of mother-to-child transmission (MTCT). METHODS: Peripheral blood mononuclear cell samples from HIV-1-infected women enrolled in a prospective cohort study in Argentina, the Bahamas, Brazil, and Mexico (NISDI Perinatal Study) were assayed for PRMs. Eligible women were those enrolled by March 2005 and diagnosed with HIV-1 infection during the current pregnancy, and who received ART for MTCT prophylaxis and were followed for 6-12 weeks postpartum. RESULTS: Of 819 women, 198 met the eligibility criteria. At enrollment, 98% were asymptomatic, 62% had plasma viral load < 1000 copies/ml, 53% had CD4+ cell count > or = 500 cells/microl, and 78% were ART-exposed (mean duration, 8.0 weeks; 95% confidence interval, 7.1-8.9). The most complex ART regimen during pregnancy was usually (81%) a three-drug regimen [two nucleoside reverse transcriptase inhibitors (NRTIs) + one protease inhibitor or two NRTIs + one non-nucleoside reverse transcriptase inhibitor). PRMs were observed in samples from 19 (16%) of 118 women that were amplifiable at one or both time points [11/76 (14%) at enrollment; 14/97 (14%) at 6-12 weeks]. The occurrence of PRMs was not associated with clinical, immunological, or virological disease stage at either time point, whether ART-naive versus exposed at enrollment, or the most complex or number of antiretroviral drug regimens received during pregnancy (P > 0.1). Of 55 women with amplifiable samples at both time points, PRMs were detected in 11 samples (20%). CONCLUSIONS: PRMs occurred among 16.1% of relatively healthy HIV-1-infected mothers from Latin American and Caribbean countries receiving MTCT prophylaxis.

Drug-resistance surveillance among newly HIV-1 diagnosed individuals in Buenos Aires, Argentina.

OBJECTIVE: Our objective was to estimate primary resistance in an urban setting in a developing country with a long history of antiretroviral delivery and high coverage levels. DESIGN: We carried out a resistance surveillance study according to WHO HIV-Resistance Guidelines. METHODS: Blood samples were collected from 323 drug-naive HIV-1 infected individuals diagnosed at two HIV voluntary counselling and testing centers in Buenos Aires. Viral-load, CD4 cell counts and detuned assays were performed on all samples. The pol gene was sequenced and the resistance profile determined. Phylogenetic analysis was performed by neighbor-joining trees and bootscanning analysis. RESULTS: We found that 12 (4.2%) of the 284 samples sequenced harbored primary resistance mutations, of which K103N, M41L and V108I were most prevalent. Phylogenetic analysis revealed evidence for the transmission of the K103N mutation among the drug-naive population. The proportion of recent infections identified by the detuned assay was 10.1%. CONCLUSIONS: Levels of primary resistance in Buenos Aires are still low, despite a long history of ARV delivery and high coverage levels.