[Show abstract][Hide abstract] ABSTRACT: HIV infection and antiretroviral therapy (ART) may create unique risk factors for vitamin D insufficiency, including alterations of vitamin D metabolism by ART. We prospectively compared demographic and clinical parameters between vitamin D sufficient and insufficient HIV-infected (HIV+) adults, and assessed changes in these parameters among insufficient participants following standardized vitamin D supplementation.
HIV+ adults (≥18 years old) with HIV-1 RNA <50 copies/mL on ART were enrolled. Vitamin D sufficiency and insufficiency were defined as 25-hydroxyvitamin D (25(OH)D) ≥30 or <30 ng/mL, respectively. Insufficient participants received open-label vitamin D3 50,000 IU twice weekly for 5 weeks, then 8000 IU twice weekly to complete 24 weeks. The primary endpoint was success or failure to achieve 25(OH)D ≥30 ng/mL at week 24.
Ninety-seven participants enrolled (34 vitamin D sufficient, 63 insufficient); 32 % female, 47 % non-White, median age 46 years, ART duration 5 years, CD4+ T lymphocyte count (CD4) 673 cells/mm(3). 25(OH)D repletion was 83 % (95 % CI 71 %-90 %) successful. 25(OH)D levels correlated with both CD4 (r = 0.44, p = 0.01) and time on protease inhibitor (r = -0.35, p = 0.01). After adjusting for age, sex, race, nadir CD4 and baseline 25(OH)D: 1) current use of efavirenz exposure was associated with a 21.1 ng/mL higher week 24 25(OH)D level (p = 0.007), 2) per year use of zidovudine was associated with 7.1 ng/mL reduction in week 24 serum 25(OH)D (p = 0.05) and 3) every 1 ng/mL 25(OH)D increase was associated with a 3.3 cell/mm(3) CD4 increase (p = 0.06).
Vitamin D3 supplementation was effective in repleting 25(OH)D levels after 24 weeks. Current efavirenz use was positively associated with post-repletion 25(OH)D levels, while greater time on zidovudine was associated with lower post-repletion 25(OH)D levels. The association between improved CD4 recovery and vitamin D repletion suggests a potential benefit of vitamin D supplementation on immunologic recovery during HIV treatment.
This trial is registered at The Brazilian Clinical Trials Registry ( U1111-1165-2537 ).
[Show abstract][Hide abstract] ABSTRACT: HIV-infected individuals have a higher risk of serious illnesses following infection by infection with influenza. Although anti-influenza vaccination is recommended, immunosuppression may limit their response to active immunization. We followed-up a cohort of HIV-infected individuals vaccinated against influenza to assess the immunogenicity and sustainability of the immune response to vaccination. Individuals were vaccinated 2011 with inactivated triple influenza vaccine (TIV), and they had received in 2010 the monovalent anti-A(H1N1)pdm09 vaccine. The sustainability of the immune response to A(H1N1)pdm09 at 12 months after monovalent vaccination fell, both in individuals given two single or two double doses. For these individuals, A(H1N1)pdm09 component from TIV acted as a booster, raising around 40% the number of seroprotected individuals. Almost 70% of the HIV-infected individuals were already seroprotected to A/H3N2 at baseline. Again, TIV boosted over 90% the seroprotection to A/H3N2. Anti-A/H3N2 titers dropped by 20% at 6 months after vaccination. Pre-vaccination seroprotection rate to influenza B (victoria lineage) was the lowest among those tested, seroconversion rates were higher after vaccination. Seroconversion/protection after TIV vaccination did not differ significantly across categories of clinical and demographic variables. Anti-influenza responses in Brazilian HIV-infected individuals reflected both the previous history of virus circulation in Brazil and vaccination. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Journal of Medical Virology 08/2015; DOI:10.1002/jmv.24351 · 2.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective To determine the prevalence of adequate monitoring and the costs of measuring CD4+ T-lymphocytes (CD4+ cell) and human immunodeficiency virus (HIV) viral load in people receiving antiretroviral therapy (ART) in seven countries in the WHO Region of the Americas. Methods We obtained retrospective, longitudinal data for 14 476 adults who started a first ART regimen at seven HIV clinics in Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru between 2000 and 2011. We estimated the proportion of 180-day periods with adequate monitoring, which we defined as at least one CD4+ cell count and one viral load measurement. Factors associated with adequate monitoring were analysed using regression methods. The costs of the tests were estimated. Findings The median follow-up time was 50.4 months; the proportion of 180-day periods with adequate CD4+ cell counts was 69% while the proportion with adequate monitoring was 62%. Adequate monitoring was more likely in participants who were older, who started ART more recently, whose first regimen included a non-nucleoside reverse transcriptase inhibitor or who had a CD4+ cell count less than 200 cells/Ml at ART initiation. The cost of one CD4+ cell count ranged from 7.37 United States dollars (US$) in Argentina to US$ 64.09 in Chile; the cost of one viral load measurement ranged from US$ 20.34 in Brazil to US$ 186.28 in Haiti. Conclusion In HIV-infected participants receiving ART in the WHO Region of the Americas, CD4+ cell count and viral load monitoring was often carried out less frequently than regional guidelines recommend. The laboratory costs of monitoring varied greatly.
Bulletin of the World Health Organisation 08/2015; 93(8):529-539. DOI:10.2471/BLT.14.147447 · 5.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction:
The World Health Organization recently released guidelines on the use of pre-exposure prophylaxis (PrEP) for prevention of HIV infection among men and transgender women (TGW) who have sex with men based on results of randomized clinical trials. The aim of this commentary is to discuss the opportunities and challenges of incorporating PrEP into the Brazilian continuum of HIV care and prevention for men who have sex with men (MSM) and TGW.
Key aspects of the AIDS epidemic among MSM and TGW in Brazil and the comprehensive Brazilian response to the epidemic are presented. The universal access to health care provided through the Brazilian Unified Health System (SUS) and the range of prevention and care services already available countrywide to HIV-positive individuals and at-risk MSM and TGW are identified as the main facilitators for the implementation of PrEP. Limited PrEP awareness among MSM, TGW and health care providers, low HIV testing frequency and low HIV risk perception among MSM and TGW represent the core challenges to be addressed. Data generated by demonstration projects in Brazil will provide an important contribution to PrEP rollout in Brazil.
The implementation of PrEP in Brazil is feasible. A synergistic rollout of treatment as prevention and PrEP will maximize public health and individual benefits of the country's comprehensive response to the AIDS epidemic.
Journal of the International AIDS Society 07/2015; 18(4 Suppl 3):20010. DOI:10.7448/IAS.18.4.20010 · 5.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Sexually transmitted diseases (STD) are frequently asymptomatic and increase the likelihood of transmitting and acquiring HIV. In Brazil, the guidelines for STDs diagnosis and treatment are based on the syndromic approach. Nucleic acid amplification tests (NAAT) has been recommended as routine STDs screening in some countries, especially for men who have sex with men (MSM). Limited data are available about how to best define target groups for routine screening by NAATs within this population. We aimed to assess the prevalence of rectal and urethral Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections and syphilis, and the factors associated with having at least one STD among HIV-infected and uninfected MSM in Rio de Janeiro, Brazil.
From August 2010 to June 2012, 391 MSM were enrolled into the Evandro Chagas National Institute of Infectious Diseases-INI-Fiocruz cohort, and 292 MSM (HIV-infected:211 and HIV-uninfected:81) were included in this study. NAATs were performed on the rectal swabs and urine for CT and NG. The rapid plasma reagin test and microhemagglutination assay for Treponema pallidum were performed for syphilis diagnosis.
The overall prevalence of STD was 20.0% (95%CI:15.7-25.1): 10% anorectal chlamydia; syphilis 9.9%; anorectal gonorrheae 2.5%; and urethral chlamydia 2.2%; no case of urethral gonorrheae was detected. The proportion of HIV-positive MSM who had at least one STD was nearly two times that of HIV-negative MSM (22.6% vs 13.2%; P = 0.09). The frequency of each STD, except for anorectal NG (1.5% vs.5.2%), was higher among HIV-positive than HIV-negative individuals. Among the 211 asymptomatic participants, 17.5% (n = 37) were identified as having at least one STD; 10.4% (n = 22/211) tested positive for anorectal chlamydia. Sixty five percent of HIV-positive MSM were asymptomatic at the time of the STD diagnosis, while 100.0% of the HIV-negative MSM. Age (APR = 0.78; 95%CI:0.60-1.00 for each additional ten years) and a positive-HIV serostatus (APR = 2.05; 95%CI:1.03-4.08) were significantly associated with STD diagnosis.
An overall high STD-prevalence rate was observed, especially among HIV-infected and in younger individuals, and the majority of STDs were asymptomatic. STD screening using NAATs among asymptomatic MSM is a potentially cost-effective intervention for the prevention of HIV infection among MSM.
BMC Public Health 07/2015; 15(1):686. DOI:10.1186/s12889-015-2002-0 · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Long-term survival of HIV patients after initiating highly active antiretroviral therapy (ART) has not been sufficiently described in Latin America and the Caribbean, as compared to other regions. The aim of this study was to describe the incidence of mortality, loss to follow-up (LTFU) and associated risk factors for patients enrolled in the Caribbean, Central and South America Network (CCASAnet).
We assessed time from ART initiation (baseline) to death or LTFU between 2000 and 2014 among ART-naïve adults (≥18 years) from sites in seven countries included in CCASAnet: Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru. Kaplan-Meier techniques were used to estimate the probability of mortality over time. Risk factors for death were assessed using Cox regression models stratified by site and adjusted for sex, baseline age, nadir pre-ART CD4 count, calendar year of ART initiation, clinical AIDS at baseline and type of ART regimen.
A total of 16,996 ART initiators were followed for a median of 3.5 years (interquartile range (IQR): 1.6-6.2). The median age at ART initiation was 36 years (IQR: 30-44), subjects were predominantly male (63%), median CD4 count was 156 cells/µL (IQR: 60-251) and 26% of subjects had clinical AIDS prior to starting ART. Initial ART regimens were predominantly non-nucleoside reverse transcriptase inhibitor based (86%). The cumulative incidence of LTFU five years after ART initiation was 18.2% (95% confidence interval (CI) 17.5-18.8%). A total of 1582 (9.3%) subjects died; the estimated probability of death one, three and five years after ART initiation was 5.4, 8.3 and 10.3%, respectively. The estimated five-year mortality probability varied substantially across sites, from 3.5 to 14.0%. Risk factors for death were clinical AIDS at baseline (adjusted hazard ratio (HR)=1.65 (95% CI 1.47-1.87); p<0.001), lower baseline CD4 (HR=1.95 (95% CI 1.63-2.32) for 50 vs. 350 cells/µL; p<0.001) and older age (HR=1.47 (95% CI 1.29-1.69) for 50 vs. 30 years at ART initiation; p<0.001).
In this large, long-term study of mortality among HIV-positive adults initiating ART in Latin America and the Caribbean, overall estimates of mortality were heterogeneous, generally falling between those reported in high-income countries and sub-Saharan Africa.
Journal of the International AIDS Society 07/2015; 18(1):20016. DOI:10.7448/IAS.18.1.20016 · 5.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We describe CD4 counts at 6-month intervals for 5 years after combination antiretroviral therapy initiation among 12 879 antiretroviral-naive
human immunodeficiency virus-infected adults from Latin America and the Caribbean. Median CD4 counts increased from 154 cells/mm3 at baseline (interquartile range [IQR], 60–251) to 413 cells/mm3 (IQR, 234–598) by year 5.
[Show abstract][Hide abstract] ABSTRACT: In Brazil, the rate of cervical cancer remains high despite the availability of screening programs. With ongoing vaccine development and implementation, information on the prevalence of specific HPV types is needed, particularly among high-risk populations, such as HIV-infected women.
We performed a study of HIV-infected women in Rio de Janeiro, Brazil, who underwent cervical HPV genotype testing between 2005-2013. We examined the prevalence of high-risk HPV types and the patterns of high-risk HPV type clustering. Using logarithmic binomial regression, we estimated the risk of abnormal cytology by HPV genotype result.
Of the 562 women included, 498 (89 %) had at least one HPV type detected. 364 women (65 %) had at least one high-risk HPV type detected and 181 (32 %) had more than one high-risk type detected. HPV 58 was the most frequent HPV type detected overall (prevalence 19.8 % [95 % confidence interval 16.4-23.1]), followed by HPV 53 (prevalence 15.5 % [12.5-18.5]) and HPV 16 (prevalence 13 % [10.2-15.8]). Women infected with more than one high-risk HPV type were younger, had lower CD4+ lymphocyte counts, and were more likely to be infected with HPV 16 or 18. In adjusted analyses, presence of more than one high-risk HPV type was associated with a two-fold increased risk of abnormal cytology after adjusting for presence of individual high-risk type, age, and CD4+ lymphocyte count (adjusted prevalence ratios 1.88-2.07, all p <0.001). No single high-risk HPV type was statistically associated with abnormal cytology after adjusting for the presence of more than one high-risk HPV type.
In the largest study of cervical HPV genotypes among HIV-infected women in Latin America, infection by high-risk HPV types other than 16 or 18 and infection by more than one high-risk HPV types were common. Infection by more than one high-risk type was more strongly associated with abnormal cervical cytology than any individual high-risk HPV type, highlighting the need for multi-valent HPV vaccines.
BMC Cancer 06/2015; 15(1):478. DOI:10.1186/s12885-015-1486-4 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Rifampicin (RIF) induces UGT1A1, an enzyme involved in raltegravir (RAL) elimination, thereby potentially lowering RAL exposure. We examined the pharmacokinetics of RAL in human immunodeficiency virus (HIV)-infected patients on RIF-based antitubercular therapy in the French National Agency for HIV/AIDS and Viral Hepatitis Research 12 180 Reflate Tuberculosis trial.
Patients started RAL in combination with tenofovir disoproxil fumarate and lamivudine after initiation of RIF (10 mg/kg/day). In arm 1 (n = 21), they received 400 mg RAL twice daily; in arm 2 (n = 16), they received RAL 800 mg twice daily initially then 400 mg twice daily 4 weeks after RIF discontinuation. Pharmacokinetic sampling was performed over 12-hour periods, 4 weeks after initiation of RAL together with RIF (period 1), 4 weeks after RIF discontinuation (period 2), and after the RAL dose reduction in arm 2 (period 3).
In arm 1, the geometric mean ratio (GMR) between period 1 and period 2 was 0.94 (90% confidence interval [CI], .64-1.37) for the 12-hour area under the time-concentration curve (AUC0-12), and 0.69 (90% CI, .42-1.13) for the concentration at 12 hours (C12). In arm 2, the corresponding GMRs were 0.75 (90% CI, .48-1.17) and 1.10 (90% CI, .61-2.00) for period 1 vs period 2, and 1.10 (90% CI, .78-1.55) and 1.68 (90% CI, .88-3.23) for period 1 vs period 3.
The double dose of RAL overcompensated for RIF induction, but the standard dose was associated with only small decreases in AUC0-12 and C12 during RIF coadministration, warranting further evaluation in patients with HIV/tuberculosis coinfection.
[Show abstract][Hide abstract] ABSTRACT: Background. The Pan-American Health Organization has called for reducing HIV mother-to-child transmission (MTCT) to ≤0.30 infections per 1000 live births (LB), HIV MTCT risk to ≤2.0%, and congenital syphilis (CS) incidence to ≤0.50/1000LB in the Americas by 2015. Methods. Using published Brazilian data in a mathematical model, we simulated a cohort of pregnant women from antenatal care (ANC) through birth. We investigated two scenarios: (1) “current access” (89.1% receive an ANC syphilis test and 41.1% receive two; 81.7% receive an ANC HIV test and 18.9% receive birth tests; if diagnosed, 81.0% are treated for syphilis and 87.5% are treated for HIV) and (2) “ideal access” (95% of women undergo two HIV and syphilis screenings; 95% receive appropriate treatment). We conducted univariate and multivariate sensitivity analyses on key inputs. Results. With “current access,” we projected 2.95 CS cases/1000LB, 0.29 HIV infections/1000LB, 7.1% HIV MTCT risk, and 11.11 intra-uterine fetal demises (IUFD)/1000 pregnancies, with significant regional variation. With “ideal access,” we projected improved outcomes: 1.00 CS cases/1000LB, 0.10 HIV infections/1000LB, HIV MTCT risk of 2.4%, and 10.65 IUFD/1000 pregnancies. Increased testing drove the greatest improvements. Even with “ideal access,” only HIV infections/1000LB met elimination goals. Achieving all targets required testing and treatment >95% and reductions in prevalence and incidence of HIV and syphilis. Conclusions. Increasing access to care and HIV and syphilis antenatal testing will substantially reduce HIV and syphilis MTCT in Brazil. Additional, regionally-tailored interventions reducing syphilis incidence and prevalence and supporting HIV treatment adherence are necessary to completely meet targets.
[Show abstract][Hide abstract] ABSTRACT: Background: Combination antiretroviral therapy (ART) for HIV-1–infected individuals prevents sexual transmission if viral load is suppressed. Methods: Participants were HIV-1–infected partners randomized to early ART (CD4 350–550) in HPTN052 (n = 886, median follow-up = 2.1 years), a clinical trial of early ART to prevent sexual transmission of HIV-1 in serodiscordant couples at 13 sites in 9 countries. Adherence was assessed through pill count (dichotomized at <95%) and through self-report items. Predictors of adherence were mental health and general health perceptions, substance use, binge drinking, social support, sexual behaviors, and demographics. Viral suppression was defined as HIV plasma viral load <400 copies per milliliter. Adherence counseling and couples' counseling about safer sex were provided. Logistic and linear regression models using generalized estimating equation for repeated measurements were used. Findings: Through pill count, 82% of participants were adherent at 1 month and 83.3% at 1 year. Mental health was the only psychosocial variable associated with adherence [pill count, odds ratios (OR) = 1.05, 95% confidence intervals (CIs): 1.00 to 1.11; self-report parameter estimate, OR = 0.02, 95% CI: 0.01 to 0.04], although regional differences emerged. Pill count (OR = 1.19, 95% CI: 1.10 to 1.30) and self-report (OR = 1.42, 95% CI: 1.14 to 1.77) adherence were associated with viral suppression. Interpretation: Although adherence was high among individuals in stable relationships taking ART for prevention, mental health and adherence covaried. Assessing and intervening on mental health in the context of promoting adherence to ART as prevention should be explored. Adherence and couples' counseling, feedback about viral suppression, and/or altruism may also help explain the magnitude of adherence observed.
[Show abstract][Hide abstract] ABSTRACT: Despite the success of combination antiretroviral therapy (cART), a subset of HIV-infected patients who initiate cART develop early clinical progression to AIDS; therefore some cART initiators are not fully benefitted by cART. Immune activation pre-cART may predict clinical progression in cART initiators.
A case-cohort study (n=470) within the multinational Prospective Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS) clinical trial (1571 HIV treatment-naïve adults who initiated cART; CD4+ T cell count <300 cells/mm; nine countries) was conducted. A subcohort of 30 participants/country was randomly selected; additional cases were added from the main cohort. Cases (n=236 [random subcohort-36; main cohort-200]) had clinical progression (incident WHO Stage 3/4 event or death) within 96 weeks following cART initiation. Immune activation biomarkers were quantified pre-cART. Associations between biomarkers and clinical progression were examined using weighted multivariable Cox-proportional hazards models.
Median age was 35 years, 45% were women, 49% black, 31% Asian, and 9% white. Median CD4+ T-cell count was 167 cells/mm. In multivariate analysis, highest quartile CRP concentration (adjusted hazards ratio [aHR] 2.53, 95%CI 1.02-6.28) and CD4+ T-cell activation (aHR 5.18, 95CI 1.09-24.47) were associated with primary outcomes, compared to lowest quartiles. sCD14 had a trend towards association with clinical failure (aHR 2.24, 95%CI 0.96-5.21).
Measuring CRP and CD4+ T-cell activation may identify patients with CD4+ T cell counts < 300 cells/mm at risk for early clinical progression when initiating cART. Additional vigilance and symptom-based screening may be required in this subset of patients even after beginning cART.
[Show abstract][Hide abstract] ABSTRACT: Worldwide, 50% of human immunodeficiency virus (HIV)-infected people are women. This study was to evaluate whether the safety and efficacy outcomes of three initial antiretroviral regimens (ARVs) differed by sex.
Antiretroviral regimen naive participants from nine countries in four continents were assigned to ARVs with efavirenz (EFV) plus lamivudine-zidovudine, atazanavir (ATV) plus didanosine (ddI)-EC/emtricitabine (FTC) or EFV plus FTC-tenofovir-DF. The primary objective was to estimate the sex difference on efficacy outcome of treatment failure defined as one of the following: 1. Time to 1st of confirmed virologic failure, 2. WHO Stage 4 progression or 3. death with hazard ratio (HR) and 95% confidence interval (CI) from adjusted Cox regression models.
In all, 739 (47%) women and 832 (53%) men with HIV were evaluated. Women had higher pretreatment CD4+(182 vs 165 cells/mm(3); P < 0.001) and lower HIV-1 RNA (4.9 log10 vs 5.2 log10 copies/ml; P < 0.001) compared to men. Association of sex with time to regimen failure differed by treatment arm (P = 0.018). For atazanavir plus didanosine-EC plus emtricitabine, women had a longer time to treatment failure compared to men [adjusted HR (aHR) = 0.59; 95% CI 0.40-0.87]. Women were less likely to prematurely discontinue treatment prematurely (aHR = 0.74; 95% CI 0.56-0.98). Women assigned to efavirenz plus lamivudine-zidovudine were more likely to have a primary safety event compared to men (aHR = 1.49; 95% CI 1.18-1.88).
Antiretroviral efficacy and safety differed by sex in this study. Consideration of potential effects of sex on antiretroviral outcomes is important for the design of future clinical trials and for HIV treatment guidelines.
HIV Clinical Trials 05/2015; 16(3):1528433614Z0000000013. DOI:10.1179/1528433614Z.0000000013 · 2.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Men who have sex with men (MSM) in the Americas require targeted, combination HIV prevention approaches. We solicited client and provider perspectives on emerging prevention interventions including HIV pre-exposure prophylaxis (PrEP) and HIV self-tests through focus groups and in-depth interviews with 130 MSM and 41 providers across four sites: New York, San Francisco, Lima, and Rio de Janeiro. Among the MSM participants, we identified three prevention typologies: non-condom users, inconsistent condom users, and consistent condom users. Northern and Southern MSM differed in the variety of harm reduction strategies utilized: where U.S. MSM relied on condom use as well as disclosure and seroadaptive behaviors for prevention, condom use without disclosure or serostatus discussions was the norm in South America. Interest in new prevention technologies was shaped by the social context. U.S. MSM preferences differed by typology, such that non-condom users were interested in taking PrEP and using home HIV tests. MSM in Brazil, regardless of typology, were interested in exploring new prevention options. MSM in Peru demonstrated moderate interest but were less comfortable with adopting new strategies. MSM and providers' opinions differed substantially with respect to new prevention options. Across sites, most providers were reticent to engage with new prevention options, though some NGO-based providers were more supportive of exploring new prevention tools. Both clients and providers will need to be engaged in developing integrated prevention strategies for MSM.
PLoS ONE 03/2015; 10(3):e0121044. DOI:10.1371/journal.pone.0121044 · 3.23 Impact Factor