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1.  Host Genetic Factors Associated with Symptomatic Primary HIV Infection and Disease Progression among Argentinean Seroconverters 
PLoS ONE  2014;9(11):e113146.
Variants in HIV-coreceptor C-C chemokine receptor type 5 (CCR5) and Human leukocyte antigen (HLA) genes are the most important host genetic factors associated with HIV infection and disease progression. Our aim was to analyze the association of these genetic factors in the presence of clinical symptoms during Primary HIV Infection (PHI) and disease progression within the first year.
Seventy subjects diagnosed during PHI were studied (55 symptomatic and 15 asymptomatic). Viral load (VL) and CD4 T-cell count were evaluated. HIV progression was defined by presence of B or C events and/or CD4 T-cell counts <350 cell/mm3. CCR5 haplotypes were characterized by polymerase chain reaction and SDM-PCR-RFLP. HLA-I characterization was performed by Sequencing.
Symptoms during PHI were significantly associated with lower frequency of CCR5-CF1 (1.8% vs. 26.7%, p = 0.006). Rapid progression was significantly associated with higher frequency of CCR5-CF2 (16.7% vs. 0%, p = 0.024) and HLA-A*11 (16.7% vs. 1.2%, p = 0.003) and lower frequency of HLA-C*3 (2.8% vs. 17.5%, p = 0.035). Higher baseline VL was significantly associated with presence of HLA-A*11, HLA-A*24, and absence of HLA-A*31 and HLA-B*57. Higher 6-month VL was significantly associated with presence of CCR5-HHE, HLA-A*24, HLA-B*53, and absence of HLA-A*31 and CCR5-CF1. Lower baseline CD4 T-cell count was significantly associated with presence of HLA-A*24/*33, HLA-B*53, CCR5-CF2 and absence of HLA-A*01/*23 and CCR5-HHA. Lower 6-month CD4 T-cell count was associated with presence of HLA-A*24 and HLA-B*53, and absence of HLA-A*01 and HLA-B*07/*39. Moreover, lower 12-month CD4 T-cell count was significantly associated with presence of HLA-A*33, HLA-B*14, HLA-C*08, CCR5-CF2, and absence of HLA-B*07 and HLA-C*07.
Several host factors were significantly associated with disease progression in PHI subjects. Most results agree with previous studies performed in other groups. However, some genetic factor associations are being described for the first time, highlighting the importance of genetic studies at a local level.
PMCID: PMC4236131  PMID: 25406087
2.  Changes in lipid levels after 48 weeks of dual versus triple therapy observed in the GARDEL study 
Journal of the International AIDS Society  2014;17(4Suppl 3):19554.
Treatment with ritonavir-boosted protease inhibitors and nucleoside analogues frequently leads to rises in lipids, which might increase the cardiovascular risk. The aim of this study was to describe changes in lipid levels among HIV positive patients participating in the GARDEL study.
Materials and Methods
The GARDEL study compared the efficacy and safety of a dual therapy (DT) combination of LPV/r 400/100 mg BID+3TC 150 mg BID to a triple therapy (TT) with LPV/r 400/100 mg BID+3TC or FTC and a third investigator-selected NRTI in fixed-dose combination among HIV+ treatment naïve patients. We compared changes in lipid levels from baseline to week 48 in both arms.
Patient's characteristics were well balanced regarding mean baseline total cholesterol (157 mg/dL DT, 154 mg/dL TT), triglycerides (142 mg/dL DT, 139 mg/Dl TT), LDL-C (94 mg/dL DT, 91 mg/dL TT) and HDL-C (36 mg/dL DT, 35 mg/dL TT). Changes in total cholesterol, LDL-C and HDL-C were higher in DT arm, compared to TT (32% DT vs 26% TT for cholesterol; 25% DT vs 16% TT for LDL and 33% DT vs 28% TT for HDL). Increase in triglycerides was higher in TT compared to DT (55% DT vs 92% TT) (Table 1). In TT arm LDL-C and total cholesterol elevations were lower among patients receiving TDF compared to those treated with ZDV or ABC.
Changes in lipid parameters were observed in both arms. Albeit the increase was numerically higher for cholesterol (total and LDL-C) in DT arm while TT arm had higher increases in TG; no difference was observed when week 48 values were compared with the NCEP ATP III goals for cardiovascular risk reduction [1]. So, the DT strategy, even missing the lipid-lowering effect observed with tenofovir, does not seem to add significant risk to patients treated with this novel strategy.
PMCID: PMC4224811  PMID: 25394061
3.  Factors associated with healthcare avoidance among transgender women in Argentina 
Transgender (TG) women in many settings continue to contend with barriers to healthcare, including experiences of stigma and discrimination. Argentina has a universal health care system and laws designed to promote healthcare access among TG women. However, little is known about barriers to healthcare access among TG women in this setting. The aim of this study was to explore individual, social-structural and environmental factors associated with healthcare avoidance among TG women in Argentina.
Data were derived from a 2013 nation-wide, cross-sectional study involving TG women in Argentina. We assessed the prevalence and factors associated with avoiding healthcare using multivariable logistic regression.
Among 452 TG women included in the study, 184 (40.7%) reported that they avoided seeking healthcare because of their transgender identity. In multivariable analysis, factors positively associated with avoiding seeking healthcare were: having been exposed to police violence (adjusted odd ratio [aOR] = 2.20; 95% CI: 1.26 – 3.83), internalized stigma (aOR = 1.60, 95% CI: 1.02–2.51), having experienced discrimination by healthcare workers (aOR = 3.36: 95% CI: 1.25 – 5.70) or patients (aOR = 2.57; 95% CI: 1.58 – 4.17), and currently living in the Buenos Aires metropolitan area (aOR = 2.32; 95% CI: 1.44 – 3.76). In contrast, TG women with extended health insurance were less likely to report avoiding healthcare (aOR = 0.49; 95% CI: 0.26 – 0.93).
A high proportion of TG women in our sample reported avoiding healthcare. Avoiding healthcare was associated with stigma and discrimination in healthcare settings, as well as police violence experiences. Although further research is warranted, these finding suggests that socio-structural interventions tailored TG women needs are needed to improve access to healthcare among this population.
PMCID: PMC4220051  PMID: 25261275
Transgender women; Argentina; Healthcare access; Police violence; Discrimination; Stigma
4.  Use of Third Line Antiretroviral Therapy in Latin America 
PLoS ONE  2014;9(9):e106887.
Access to highly active antiretroviral therapy (HAART) is expanding in Latin America. Many patients require second and third line therapy due to toxicity, tolerability, failure, or a combination of factors. The need for third line HAART, essential for program planning, is not known.
Antiretroviral-naïve patients ≥18 years who started first HAART after January 1, 2000 in Caribbean, Central and South America Network (CCASAnet) sites in Argentina, Brazil, Honduras, Mexico, and Peru were included. Clinical trials participants were excluded. Third line HAART was defined as use of darunavir, tipranavir, etravirine, enfuvirtide, maraviroc or raltegravir. Need for third line HAART was defined as virologic failure while on second line HAART.
Of 5853 HAART initiators followed for a median of 3.5 years, 310 (5.3%) failed a second line regimen and 44 (0.8%) received a third line regimen. Cumulative incidence of failing a 2nd or starting a 3rd line regimen was 2.7% and 6.0% three and five years after HAART initiation, respectively. Predictors at HAART initiation for failing a second or starting a third line included female sex (hazard ratio [HR] = 1.54, 95% confidence interval [CI] 1.18–2.00, p = 0.001), younger age (HR = 2.76 for 20 vs. 40 years, 95% CI 1.86–4.10, p<0.001), and prior AIDS (HR = 2.17, 95% CI 1.62–2.90, p<0.001).
Third line regimens may be needed for at least 6% of patients in Latin America within 5 years of starting HAART, a substantial proportion given the large numbers of patients on HAART in the region. Improved accessibility to third line regimens is warranted.
PMCID: PMC4164470  PMID: 25221931
5.  Towards Full Citizenship: Correlates of Engagement with the Gender Identity Law among Transwomen in Argentina 
PLoS ONE  2014;9(8):e105402.
In May 2012, Argentina passed its “Gender Identity” Law, which aimed to address the legal invisibility, discrimination and marginalization that transgender individuals have historically faced. The aim of this study was to explore factors associated with engagement with the Gender Identity Law among transwomen living in Argentina.
Data were derived from a 2013 nationwide, cross-sectional study involving transwomen in Argentina. Using multivariate logistic regression, we assessed the prevalence and factors associated with acquiring a gender-congruent identity card within the first 18 months of enactment of the Gender Identity Law.
Among 452 transwomen, 260 (57.5%) reported that they had obtained a new gender-congruent identity card. In multivariate analysis, factors positively associated with acquiring a new ID were: previously experiencing discrimination by healthcare workers (adjusted odd ratio [aOR] = 2.01, 95% CI: 1.27–3.20); having engaged in transition procedures (aOR = 3.06, 95% CI: 1.58–5.93); and having a job other than sex work (aOR = 1.81, 95% CI: 1.06–3.10). Foreign born transwomen were less likely to have obtained a new ID (aOR = 0.14, 95% CI: 0.06–0.33).
More than half of transwomen in our sample acquired a new gender-congruent ID within the first 18 months of enactment of the Gender Identity Law. However, access to and uptake of this right has been heterogeneous. In particular, our findings suggest that the most empowered transwomen may have been among the first to take advantage of this right. Although educational level, housing conditions, HIV status and sex work were not associated with the outcome, foreign-born status was a strong negative correlate of new ID acquisition. Therefore, additional efforts should be made in order to ensure that benefits of this founding policy reach all transwomen in Argentina.
PMCID: PMC4136870  PMID: 25133547
6.  Early Skewed Distribution of Total and HIV-Specific CD8+ T-Cell Memory Phenotypes during Primary HIV Infection Is Related to Reduced Antiviral Activity and Faster Disease Progression 
PLoS ONE  2014;9(8):e104235.
The important role of the CD8+ T-cells on HIV control is well established. However, correlates of immune protection remain elusive. Although the importance of CD8+ T-cell specificity and functionality in virus control has been underscored, further unraveling the link between CD8+ T-cell differentiation and viral control is needed. Here, an immunophenotypic analysis (in terms of memory markers and Programmed cell death 1 (PD-1) expression) of the CD8+ T-cell subset found in primary HIV infection (PHI) was performed. The aim was to seek for associations with functional properties of the CD8+ T-cell subsets, viral control and subsequent disease progression. Also, results were compared with samples from Chronics and Elite Controllers. It was found that normal maturation of total and HIV-specific CD8+ T-cells into memory subsets is skewed in PHI, but not at the dramatic level observed in Chronics. Within the HIV-specific compartment, this alteration was evidenced by an accumulation of effector memory CD8+ T (TEM) cells over fully differentiated terminal effector CD8+ T (TTE) cells. Furthermore, higher proportions of total and HIV-specific CD8+ TEM cells and higher HIV-specific TEM/(TEM+TTE) ratio correlated with markers of faster progression. Analysis of PD-1 expression on total and HIV-specific CD8+ T-cells from PHI subjects revealed not only an association with disease progression but also with skewed memory CD8+ T-cell differentiation. Most notably, significant direct correlations were obtained between the functional capacity of CD8+ T-cells to inhibit viral replication in vitro with higher proportions of fully-differentiated HIV-specific CD8+ TTE cells, both at baseline and at 12 months post-infection. Thus, a relationship between preservation of CD8+ T-cell differentiation pathway and cell functionality was established. This report presents evidence concerning the link among CD8+ T-cell function, phenotype and virus control, hence supporting the instauration of early interventions to prevent irreversible immune damage.
PMCID: PMC4122399  PMID: 25093660
7.  Patient–provider perceptions on engagement in HIV care in Argentina 
AIDS care  2013;26(5):602-607.
Approximately 30% of patients participating in the national antiretroviral therapy (ART) program in Argentina fail to achieve an undetectable viral load, and approximately 25% are not retained in care. This qualitative study was designed to explore and identify factors associated with engagement and retention in public and private health care in Buenos Aires, Argentina. Qualitative data from key informants (n = 12) and focus groups (n = 4 groups) of patients and providers from private and public HIV treatment facilities were recorded and transcribed. Predetermined and arising themes related to adherence, engagement, and retention in care were coded and analyzed using qualitative data analysis software. Reasons identified for patients’ lack of adherence or engagement in care differed between patients and providers, and patients attributed limitations to low self-efficacy, fear and concerns about HIV, and lack of provider involvement in treatment. In contrast, providers viewed themselves as decision-makers in patient care and patients as responsible for their own nonadherence due to lack of commitment to their own health or due to medication side effects. Patients reported health care system limitations and HIV concerns contributed to a lack of engagement, and providers identified limited HIV literacy and stigma as additional problems. Both agreed that chronic illness and substance addiction impacted adherence and retention, and agreed on the importance of trust, honesty, and communication in the patient–provider relationship. Results support the incorporation of system-, provider-, and patient-focused components into interventions to facilitate patient engagement, adherence, and retention in public and private settings in Argentina.
PMCID: PMC3966648  PMID: 24138788
HIV; adherence; engagement; communication; Argentina
8.  Early Gag Immunodominance of the HIV-Specific T-Cell Response during Acute/Early Infection Is Associated with Higher CD8+ T-Cell Antiviral Activity and Correlates with Preservation of the CD4+ T-Cell Compartment 
Journal of Virology  2013;87(13):7445-7462.
The important role of the CD8+ T-cell response on HIV control is well established. Moreover, the acute phase of infection represents a proper scenario to delineate the antiviral cellular functions that best correlate with control. Here, multiple functional aspects (specificity, ex vivo viral inhibitory activity [VIA] and polyfunctionality) of the HIV-specific CD8+ T-cell subset arising early after infection, and their association with disease progression markers, were examined. Blood samples from 44 subjects recruited within 6 months from infection (primary HIV infection [PHI] group), 16 chronically infected subjects, 11 elite controllers (EC), and 10 healthy donors were obtained. Results indicated that, although Nef dominated the anti-HIV response during acute/early infection, a higher proportion of early anti-Gag T cells correlated with delayed progression. Polyfunctional HIV-specific CD8+ T cells were detected at early time points but did not associate with virus control. Conversely, higher CD4+ T-cell set points were observed in PHI subjects with higher HIV-specific CD8+ T-cell VIA at baseline. Importantly, VIA levels correlated with the magnitude of the anti-Gag cellular response. The advantage of Gag-specific cells may result from their enhanced ability to mediate lysis of infected cells (evidenced by a higher capacity to degranulate and to mediate VIA) and to simultaneously produce IFN-γ. Finally, Gag immunodominance was associated with elevated plasma levels of interleukin 2 (IL-2) and macrophage inflammatory protein 1β (MIP-1β). All together, this study underscores the importance of CD8+ T-cell specificity in the improved control of disease progression, which was related to the capacity of Gag-specific cells to mediate both lytic and nonlytic antiviral mechanisms at early time points postinfection.
PMCID: PMC3700299  PMID: 23616666
9.  Tuberculosis in Antiretroviral Treatment Programs in Lower Income Countries: Availability and Use of Diagnostics and Screening 
PLoS ONE  2013;8(10):e77697.
In resource-constrained settings, tuberculosis (TB) is a common opportunistic infection and cause of death in HIV-infected persons. TB may be present at the start of antiretroviral therapy (ART), but it is often under-diagnosed. We describe approaches to TB diagnosis and screening of TB in ART programs in low- and middle-income countries.
Methods and findings
We surveyed ART programs treating HIV-infected adults in sub-Saharan Africa, Asia and Latin America in 2012 using online questionnaires to collect program-level and patient-level data. Forty-seven sites from 26 countries participated. Patient-level data were collected on 987 adult TB patients from 40 sites (median age 34.7 years; 54% female). Sputum smear microscopy and chest radiograph were available in 47 (100%) sites, TB culture in 44 (94%), and Xpert MTB/RIF in 23 (49%). Xpert MTB/RIF was rarely available in Central Africa and South America. In sites with access to these diagnostics, microscopy was used in 745 (76%) patients diagnosed with TB, culture in 220 (24%), and chest X-ray in 688 (70%) patients. When free of charge culture was done in 27% of patients, compared to 21% when there was a fee (p = 0.033). Corresponding percentages for Xpert MTB/RIF were 26% and 15% of patients (p = 0.001). Screening practices for active disease before starting ART included symptom screening (46 sites, 98%), chest X-ray (38, 81%), sputum microscopy (37, 79%), culture (16, 34%), and Xpert MTB/RIF (5, 11%).
Mycobacterial culture was infrequently used despite its availability at most sites, while Xpert MTB/RIF was not generally available. Use of available diagnostics was higher when offered free of charge.
PMCID: PMC3798412  PMID: 24147059
10.  Routine HIV Testing among Hospitalized Patients in Argentina. Is It Time for a Policy Change? 
PLoS ONE  2013;8(7):e69517.
The Argentinean AIDS Program estimates that 110,000 persons are living with HIV/AIDS in Argentina. Of those, approximately 40% are unaware of their status, and 30% are diagnosed in advanced stages of immunosuppression. Though studies show that universal HIV screening is cost-effective in settings with HIV prevalence greater than 0.1%, in Argentina, with the exception of antenatal care, HIV testing is always client-initiated.
We performed a pilot study to assess the acceptability of a universal HIV screening program among inpatients of an urban public hospital in Buenos Aires.
Over a six-month period, all eligible adult patients admitted to the internal medicine ward were offered HIV testing. Demographics, uptake rates, reasons for refusal and new HIV diagnoses were analyzed.
Of the 350 admissions during this period, 249 were eligible and subsequently enrolled. The enrolled population was relatively old compared to the general population, was balanced on gender, and did not report traditional high risk factors for HIV infection. Only 88 (39%) reported prior HIV testing. One hundred and ninety (76%) patients accepted HIV testing. In multivariable analysis only younger age (OR 1.02; 95%CI 1.003-1.05) was independently associated with test uptake. Three new HIV diagnoses were made (undiagnosed HIV prevalence: 1.58%); none belonged to a most-at-risk population.
Our findings suggest that universal HIV screening in this setting is acceptable and potentially effective in identifying undiagnosed HIV-infected individuals. If confirmed in a larger study, our findings may inform changes in the Argentinean HIV testing policy.
PMCID: PMC3729969  PMID: 23936034
12.  A Novel Educational Strategy Targeting Health Care Workers in Underserved Communities in Central America to Integrate HIV into Primary Medical Care 
PLoS ONE  2012;7(10):e46426.
Current educational strategies to integrate HIV care into primary medical care in Central America have traditionally targeted managers or higher-level officials, rather than local health care workers (HCWs). We developed a complementary online and on-site interactive training program to reach local HCWs at the primary care level in underserved communities.
The training program targeted physicians, nurses, and community HCWs with limited access to traditional onsite training in Panama, Nicaragua, Dominican Republic, and Guatemala. The curriculum focused on principles of HIV care and health systems using a tutor-supported blended educational approach of an 8-week online component, a weeklong on-site problem-solving workshop, and individualized project-based interventions.
Of 258 initially active participants, 225 (225/258 = 87.2%) successfully completed the online component and the top 200 were invited to the on-site workshop. Of those, 170 (170/200 = 85%) attended the on-site workshop. In total, 142 completed all three components, including the project phase. Quantitative and qualitative evaluation instruments included knowledge assessments, reflexive essays, and acceptability surveys. The mean pre and post-essay scores demonstrating understanding of social determinants, health system organization, and integration of HIV services were 70% and 87.5%, respectively, with an increase in knowledge of 17.2% (p<0.001). The mean pre- and post-test scores evaluating clinical knowledge were 70.9% and 90.3%, respectively, with an increase in knowledge of 19.4% (p<0.001). A survey of Likert scale and open-ended questions demonstrated overwhelming participant satisfaction with course content, structure, and effectiveness in improving their HIV-related knowledge and skills.
This innovative curriculum utilized technology to target HCWs with limited access to educational resources. Participants benefited from technical skills acquired through the process, and could continue working within their underserved communities while participating in the online component and then implement interventions that successfully converted theoretical knowledge to action to improve integration of HIV care into primary care.
PMCID: PMC3480350  PMID: 23115628
13.  Acute HIV Seroconversion Presenting with Active Tuberculosis and Associated with High Levels of T-Regulatory Cells 
Viral Immunology  2011;24(4):347-349.
A patient with well-defined acute HIV infection who developed concomitant pulmonary tuberculosis during the retroviral acute syndrome is reported here. In this patient high levels of T-regulatory cells (Tregs) and a low proliferation response to M. tuberculosis were initially detected, which normalized throughout follow-up. This case calls for the consideration of tuberculosis in patients in the early stages of HIV, and emphasizes the need for further study of the potential causal relationship between Treg cells and the risk of TB reactivation in HIV patients.
PMCID: PMC3192184  PMID: 21774688
14.  ICOS, SLAM and PD-1 expression and regulation on T lymphocytes reflect the immune dysregulation in patients with HIV-related illness with pulmonary tuberculosis 
Tuberculosis (TB) continues to be the most frequent cause of illness and death from an infectious agent globally, and its interaction with HIV is having devastating effects. To investigate how HIV alters the immune response to Mycobacterium tuberculosis (Mtb), we assessed basal and Mtb-induced proliferation, cytokine production, and expression of signalling lymphocytic activation molecule (SLAM), inducible costimulator (ICOS) and programmed death-1 (PD-1) on T lymphocytes from HIV-positive individuals coinfected with TB, HIV-positive subjects, TB patients and healthy donors (HD).
HIV-TB patients showed increased ICOS, SLAM and PD-1 basal levels on T lymphocytes, whereas HIV-positive individuals displayed elevated levels of SLAM and PD-1, TB patients high levels of SLAM, and HD low levels of the three proteins. Mtb-stimulation enhanced ICOS expression in the four groups, but only TB and HD increased SLAM and PD-1 levels.
These data show the immune deregulation that takes place during the immune response against TB in different study populations.
PMCID: PMC3499801  PMID: 22713261
human; AIDS; tuberculosis; T cells; ICOS; SLAM; PD-1; cytokines
15.  Dynamics of Adrenal Steroids Are Related to Variations in Th1 and Treg Populations during Mycobacterium tuberculosis Infection in HIV Positive Persons 
PLoS ONE  2012;7(3):e33061.
Tuberculosis (TB) remains the most frequent cause of illness and death from an infectious agent, and its interaction with HIV has devastating effects. We determined plasma levels of dehydroepiandrosterone (DHEA), its circulating form DHEA-suphate (DHEA-s) and cortisol in different stages of M. tuberculosis infection, and explored their role on the Th1 and Treg populations during different scenarios of HIV-TB coinfection, including the immune reconstitution inflammatory syndrome (IRIS), a condition related to antiretroviral treatment. DHEA levels were diminished in HIV-TB and HIV-TB IRIS patients compared to healthy donors (HD), HIV+ individuals and HIV+ individuals with latent TB (HIV-LTB), whereas dehydroepiandrosterone sulfate (DHEA-s) levels were markedly diminished in HIV-TB IRIS individuals. HIV-TB and IRIS patients presented a cortisol/DHEA ratio significantly higher than HIV+, HIV-LTB and HD individuals. A positive correlation was observed between DHEA-s and CD4 count among HIV-TB individuals. Conversely, cortisol plasma level inversely correlated with CD4 count within HIV-TB individuals. M. tuberculosis-specific Th1 lymphocyte count was increased after culturing PBMC from HIV-TB individuals in presence of DHEA. We observed an inverse correlation between DHEA-s plasma level and Treg frequency in co-infected individuals, and CD4+FoxP3+ Treg frequency was increased in HIV-TB and IRIS patients compared to other groups. Strikingly, we observed a prominent CD4+CD25-FoxP3+ population across HIV-TB and HIV-TB IRIS patients, which frequency correlated with DHEA plasma level. Finally, DHEA treatment negatively regulated FoxP3 expression without altering Treg frequency in co-infected patients. These data suggest an enhancing role for DHEA in the immune response against M. tuberculosis during HIV-TB coinfection and IRIS.
PMCID: PMC3303789  PMID: 22431997
17.  Acute retroviral syndrome and high baseline viral load are predictors of rapid HIV progression among untreated Argentinean seroconverters 
Diagnosis of primary HIV infection (PHI) has important clinical and public health implications. HAART initiation at this stage remains controversial.
Our objective was to identify predictors of disease progression among Argentinean seroconverters during the first year of infection, within a multicentre registry of PHI-patients diagnosed between 1997 and 2008. Cox regression was used to analyze predictors of progression (LT-CD4 < 350 cells/mm3, B, C events or death) at 12 months among untreated patients.
Among 134 subjects, 74% presented with acute retroviral syndrome (ARS). Seven opportunistic infections (one death), nine B events, and 10 non-AIDS defining serious events were observed. Among the 92 untreated patients, 24 (26%) progressed at 12 months versus three (7%) in the treated group (p = 0.01). The 12-month progression rate among untreated patients with ARS was 34% (95% CI 22.5-46.3) versus 13% (95% CI 1.1-24.7) in asymptomatic patients (p = 0.04). In univariate analysis, ARS, baseline LT-CD4 < 350 cells/mm3, and baseline and six-month viral load (VL) > 100,000 copies/mL were associated with progression. In multivariate analysis, only ARS and baseline VL > 100,000 copies/mL remained independently associated; HR: 8.44 (95% CI 0.97-73.42) and 9.44 (95% CI 1.38-64.68), respectively.
In Argentina, PHI is associated with significant morbidity. HAART should be considered in PHI patients with ARS and high baseline VL to prevent disease progression.
PMCID: PMC3179691  PMID: 21831310
18.  Rates and Reasons for Early Change of First HAART in HIV-1-Infected Patients in 7 Sites throughout the Caribbean and Latin America 
PLoS ONE  2010;5(6):e10490.
HAART rollout in Latin America and the Caribbean has increased from approximately 210,000 in 2003 to 390,000 patients in 2007, covering 62% (51%–70%) of eligible patients, with considerable variation among countries. No multi-cohort study has examined rates of and reasons for change of initial HAART in this region.
Antiretroviral-naïve patients > = 18 years who started HAART between 1996 and 2007 and had at least one follow-up visit from sites in Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru were included. Time from HAART initiation to change (stopping or switching any antiretrovirals) was estimated using Kaplan-Meier techniques. Cox proportional hazards modeled the associations between change and demographics, initial regimen, baseline CD4 count, and clinical stage.
Principal Findings
Of 5026 HIV-infected patients, 35% were female, median age at HAART initiation was 37 years (interquartile range [IQR], 31–44), and median CD4 count was 105 cells/uL (IQR, 38–200). Estimated probabilities of changing within 3 months and one year of HAART initiation were 16% (95% confidence interval (CI) 15–17%) and 28% (95% CI 27–29%), respectively. Efavirenz-based regimens and no clinical AIDS at HAART initiation were associated with lower risk of change (hazard ratio (HR) = 1.7 (95% CI 1.1–2.6) and 2.1 (95% CI 1.7–2.5) comparing neverapine-based regimens and other regimens to efavirenz, respectively; HR = 1.3 (95% CI 1.1–1.5) for clinical AIDS at HAART initiation). The primary reason for change among HAART initiators were adverse events (14%), death (5.7%) and failure (1.3%) with specific toxicities varying among sites. After change, most patients remained in first line regimens.
Adverse events were the leading cause for changing initial HAART. Predictors for change due to any reason were AIDS at baseline and the use of a non-efavirenz containing regimen. Differences between participant sites were observed and require further investigation.
PMCID: PMC2879360  PMID: 20531956

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