-
Beatriz Grinsztejn,
Paula M Luz,
Antonio G Pacheco,
Desiree V G Santos,
Luciane Velasque,
Ronaldo I Moreira,
Maria Regina C Guimarães,
Estevão P Nunes,
Alberto S Lemos,
Sayonara R Ribeiro,
Dayse P Campos,
Marco A A Vitoria, Valdilea G Veloso
[show abstract]
[hide abstract]
ABSTRACT: We describe temporal trends in the mortality rates and factors associated with AIDS and non-AIDS related mortality at the Evandro Chagas Clinical Research Institute (IPEC), Oswaldo Cruz Foundation (FIOCRUZ).
Adult patients enrolling from 1986 through 2009 with a minimum follow up of 60 days were included. Vital status was exhaustively checked using patients' medical charts, through active contact with individuals and family members and by linkage with the Rio de Janeiro Mortality database using a previously validated algorithm. The CoDe protocol was used to establish the cause of death. Extended Cox proportional hazards models were used for multivariate modeling.
A total of 3530 individuals met the inclusion criteria, out of which 868 (24.6%) deceased; median follow up per patient was 3.9 years (interquartile range 1.7-9.2 years). The dramatic decrease in the overall mortality rates was driven by AIDS-related causes that decreased from 9.19 deaths/100PYs n 1986-1991 to 1.35/100PYs in 2007-2009. Non-AIDS related mortality rates remained stable overtime, at around 1 death/100PYs. Immunodeficiency significantly increased the hazard of both AIDS-related and non-AIDS-related causes of death, while HAART use was strongly associated with a lower hazard of death from either cause.
Our results confirm the remarkable decrease in AIDS-related mortality as the HIV epidemic evolved and alerts to the conditions not traditionally related to HIV/AIDS which are now becoming more frequent, needing careful monitoring.
PLoS ONE 01/2013; 8(4):e59768. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Background: Transmission of drug resistant HIV-1 strains has been gaining attention and is becoming a growing problem throughout the world. The aim of this study was to determine the prevalence of transmitted drug resistance mutations (TDRM) among antiretroviral (ARV)-naïve HIV-infected pregnant women in Rio de Janeiro, Brazil. Methods: ARV-naïve pregnant women were recruited at Hospital Geral de Nova Iguacu (HGNI), Rio de Janeiro, from 2005-2008. HIV genotyping was carried out using ViroSeq (Abbott v 2.0). TDRM were detected using the Calibrated Population Resistance Tool -CPR v. 6.0.The prevalence of mutations associated with resistance in the protease and reverse transcriptase regions of the HIV genome were assessed in samples collected prior to initiation of ARV prophylaxis or treatment. Results: Among 238 eligible specimens that were collected, 197 samples were successfully amplified using reverse transcription polymerase chain reaction. Eighty one percent of women were infected with HIV subtype B, 10% with subtype F1 viruses, 1.0% with subtype C virus and 8.0% with recombinant forms of the virus. The prevalence of HIV TDRM was 5.6% for nucleoside reverse transcriptase inhibitors, 2.0% for non-nucleoside reverse transcriptase inhibitors and 3.0% for protease inhibitors. The overall prevalence of any drug resistance was 10.7%. There were no multiclass resistant strains identified in the analyzed samples. Conclusions: The prevalence of HIV TDRM among the pregnant women in our cohort was moderate. Resistance testing should be encouraged in Rio de Janeiro, among other locations, for all HIV- infected pregnant women prior to prevention of mother-to-child transmission of HIV.
AIDS research and human retroviruses 12/2012; · 2.18 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Tests for detection of the humoral immune response to HIV-1 have to be standardized and established, demanding regional efforts. For this purpose the Neutralizing Antibody (NAb) assay for HIV-1 in TZM-bl cells was introduced in Brazil. Twenty plasma samples from HIV-1-infected individuals were assayed: 10 progressors and 10 long-term non-progressors. These were tested against 8 env-pseudotyped viruses (psVs) in the TZM-bl NAb assay and against HIV-1 strain HTLV/IIIB (HIV-1 IIIB) in primary lymphocytes. Forty-four percent of the samples showed neutralizing titers for psVs and 55% for HIV-1 IIIB. Plasma from progressors showed a broader neutralization and a higher potency. The introduction of these reference reagents encourages the participation of Brazil in future comparative assessments of anti-HIV-1 antibodies.
AIDS research and human retroviruses 11/2012; · 2.18 Impact Factor
-
Karin Nielsen-Saines,
D Heather Watts, Valdilea G Veloso,
Yvonne J Bryson,
Esau C Joao,
Jose Henrique Pilotto,
Glenda Gray,
Gerhard Theron,
Breno Santos,
Rosana Fonseca, [......],
Ruth Dickover,
Margaret Camarca,
Mark Mirochnick,
George Siberry,
Beatriz Grinsztejn,
Ronaldo I Moreira,
Francisco I Bastos,
Jiahong Xu,
Jack Moye,
Lynne M Mofenson
[show abstract]
[hide abstract]
ABSTRACT: The safety and efficacy of adding antiretroviral drugs to standard zidovudine prophylaxis in infants of mothers with human immunodeficiency virus (HIV) infection who did not receive antenatal antiretroviral therapy (ART) because of late identification are unclear. We evaluated three ART regimens in such infants.
Within 48 hours after their birth, we randomly assigned formula-fed infants born to women with a peripartum diagnosis of HIV type 1 (HIV-1) infection to one of three regimens: zidovudine for 6 weeks (zidovudine-alone group), zidovudine for 6 weeks plus three doses of nevirapine during the first 8 days of life (two-drug group), or zidovudine for 6 weeks plus nelfinavir and lamivudine for 2 weeks (three-drug group). The primary outcome was HIV-1 infection at 3 months in infants uninfected at birth.
A total of 1684 infants were enrolled in the Americas and South Africa (566 in the zidovudine-alone group, 562 in the two-drug group, and 556 in the three-drug group). The overall rate of in utero transmission of HIV-1 on the basis of Kaplan-Meier estimates was 5.7% (93 infants), with no significant differences among the groups. Intrapartum transmission occurred in 24 infants in the zidovudine-alone group (4.8%; 95% confidence interval [CI], 3.2 to 7.1), as compared with 11 infants in the two-drug group (2.2%; 95% CI, 1.2 to 3.9; P=0.046) and 12 in the three-drug group (2.4%; 95% CI, 1.4 to 4.3; P=0.046). The overall transmission rate was 8.5% (140 infants), with an increased rate in the zidovudine-alone group (P=0.03 for the comparisons with the two- and three-drug groups). On multivariate analysis, zidovudine monotherapy, a higher maternal viral load, and maternal use of illegal substances were significantly associated with transmission. The rate of neutropenia was significantly increased in the three-drug group (P<0.001 for both comparisons with the other groups).
In neonates whose mothers did not receive ART during pregnancy, prophylaxis with a two- or three-drug ART regimen is superior to zidovudine alone for the prevention of intrapartum HIV transmission; the two-drug regimen has less toxicity than the three-drug regimen. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD] and others; ClinicalTrials.gov number, NCT00099359.).
New England Journal of Medicine 06/2012; 366(25):2368-79. · 53.30 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Due to the recent widespread availability of highly active antiretroviral therapy (HAART) in middle-income countries, there has been an increase in life expectancy for women on HAART, but no corresponding decrease in cervical cancer incidence. This study evaluates the optimal cervical cancer screening strategy for HIV-infected women in a middle-income country. We developed a mathematical model, which simulates the natural history of the HPV infection, as well as the HIV-mediated immunosupression among women in Brazil. Our model was calibrated using data from the IPEC/FIOCRUZ Women's HIV-infected cohort. The model compares the lifetime effects, costs and cost-effectiveness of strategies combining cytology, HPV DNA test and colposcopy at different screening intervals for different CD4 count strata (27 strategies in total). We found that the strategy with the best cost-effectiveness profile (cost-effectiveness ratio-U$4,911/year of life saved [YLS] and probability of being cost-effective-86%) was HPV testing followed by cytology triage every year for all HIV infected women, considering a very cost-effective threshold given by Brazil's GDP per capita (US$8,625/YLS). The results were robust to changes in the input parameters as demonstrated in one-way, scenario, threshold and probabilistic sensitivity analysis. Our study indicates that annual HPV testing followed by cytology triage for all HIV-infected women is likely to be very cost-effective in a middle-income country like Brazil. The results reflect the synergic effect of using a highly sensitive screening test (HPV DNA test) in sequence with a highly specific test (cytology).
International Journal of Cancer 09/2011; 131(2):E96-104. · 5.44 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Late presentation to HIV clinical care increases individual risk for (multiple) clinical events and death, and decreases successful response to highly active antiretroviral therapy (HAART). In Brazil, provision of HAART free of charge to all individuals infected with HIV could lead to increased testing and linkage to care.
We assessed the immune status of 2555 patients who newly presented for HIV clinical care between 1997 and 2009 at the Johns Hopkins Clinical Cohort, in Baltimore, Md, and at the Instituto de Pesquisa Clinica Evandro Chagas Clinical Cohort, in Rio de Janeiro, Brazil. The mean change in the CD4 cell count per year was estimated using multivariate linear regression models.
Overall, from 1997 to 2009, 56% and 54% of the patients presented for HIV clinical care with CD4 count ≤350 cells per cubic millimeter in Baltimore and Rio de Janeiro, respectively. On average, 75% of the patients presented with viral load >10,000 copies per millimeter. In Rio de Janeiro only, the overall adjusted per year increase in the mean CD4 cell count was statistically significant (5 cells/mm, 95% confidence interval: 1 to 10 cells/mm).
We found that, over years, the majority of patients presented late, that is, with a CD4 count <350 cells per cubic millimeter. Our findings indicate that, despite the availability of HAART for more than a decade, and mass media campaigns stimulating HIV testing in both countries, the proportion of patients who start therapy at an advanced stage of the disease is still high.
JAIDS Journal of Acquired Immune Deficiency Syndromes 08/2011; 57 Suppl 3:S171-8. · 4.43 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Information is lacking on outcomes in HIV-infected Brazilian women with CD4(+) T-cell counts >200 cells/mm(3) who initiate HAART for the prevention of mother-to-child transmission, and discontinue after delivery.
Clinical event rates after postpartum HAART discontinuation were calculated for all WHO stage 2-3 events, as well as for HIV progression warranting HAART re-initiation, defined by a WHO stage 4 event and/or CD4(+) T-cell decrease to ≤200 cells/mm(3). Predictors of the WHO stage 2-3 events and HIV progression outcomes were evaluated with Cox's proportional hazards models.
A total of 120 women were followed for a mean of 1.5 years after delivery. Overall, 26 women had 30 events as follows: 20 developed WHO stage 2-3 events, yielding an incidence rate of 13/100 person-years (PY; 95% CI 8-20); 10 developed HIV progression requiring HAART re-initiation (incidence ratio 6/100 PY, 95% CI 3-11). Among progressors, a single woman developed a WHO stage 4 clinical event and the remainder had CD4(+) T-cell decreases. Women who had baseline CD4(+) T-cell counts between 200-500 cells/mm(3) had a hazard ratio for WHO stage 2-3 events of 2.5 compared to women with baseline ≥500 cells/mm(3) (95% CI 1.0-6.3; P=0.05). The only significant predictor of HIV progression was baseline CD4(+) T-cell count (hazard ratio 0.99, 95% CI 0.98-0.99; P=0.02).
In this observational study, a baseline CD4(+) T-cell count <500 cells/mm(3) was associated with an increased risk of postpartum WHO stage 2-3 clinical events and HIV disease progression. Randomized studies are needed to further evaluate the effect of postpartum treatment discontinuation on maternal health.
Antiviral therapy 01/2011; 16(3):349-56. · 3.16 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Fifty percent of people living with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) worldwide are female. In Brazil, for example, 240,000 women are infected with HIV, rates of infection in women have increased over the last two decades, and addressing HIV prevention and treatment for women at risk for, or living with, HIV/AIDS remains a challenge. To better address the needs of women living with HIV in Brazil, the Instituto de Pesquisa Clínica Evandro Chagas - Fundação Oswaldo Cruz (IPEC-FIOCRUZ) HIV Women's Cohort was established in 1996 to study the natural history of women seeking HIV care. This analysis describes the characteristics of women in the cohort who participated in HIV clinical trials between 1999 and 2008.
A total of 736 Women's Cohort participants were in active follow-up and 665 participants from the Women's Cohort were included in univariable and multivariable analyses to determine socioeconomic and sociodemographic factors associated with women's participation in HIV clinical trials at our site.
Of the complete cohort, 23% participated in a clinical trial between January 1999 and July 2008. Odds of participation decreased for women who were younger than 35 years old, currently employed, had an HIV-positive sexual partner, and/or who reported a lifetime history of illicit drug use. Alternatively, the odds of participation increased for women who had more than 8 years of formal education, were living independently, and/or were married or cohabitating.
The rate of participation in HIV clinical trials by women in the IPEC-Fiocruz Cohort was similar to other published cohorts, but identification of local risk factors and barriers to participation remains important. Our analysis offers a novel description of the factors associated with participation in HIV clinical trials among women in care at IPEC-FIOCRUZ in Rio de Janeiro, Brazil.
HIV/AIDS - Research and Palliative Care 01/2011; 3:61-8.
-
Sandra W Cardoso,
Beatriz Grinsztejn,
Luciane Velasque, Valdilea G Veloso,
Paula M Luz,
Ruth K Friedman,
Mariza Morgado,
Sayonara R Ribeiro,
Ronaldo I Moreira,
Jeanne Keruly,
Richard D Moore
[show abstract]
[hide abstract]
ABSTRACT: Studies on the long-term safety and tolerability of HAART are scarce in developing countries. HAART has been universally available in Brazil since 1997, providing a unique opportunity to evaluate the incidence and risk factors for HAART discontinuation or modification. We analyzed retrospective data from 670 treatment-naive patients followed at the HIV cohort of Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation, in Rio de Janeiro, Brazil, who first received HAART between January 1996 and December 2006. Our four outcomes of interest were treatment failure (TF-MOD), short-term toxicity (ST-MOD), long-term toxicity (LT-MOD), and overall modification/discontinuation (MOD, composed of TF-MOD, ST-MOD, LT-MOD, and other reasons). Risk factors were assessed using Cox's proportional hazards regression. Incidences of MOD, ST-MOD, LT-MOD, and TF-MOD were 28.3, 24.0, 4.0, and 5.6 per 100 persons-years, respectively. MOD was observed in 69% of the patients; 40% of the MODs were toxicity related. The risk of MOD in the first year of treatment was 32% (95% CI: 28.3-35.5%); the median time from HAART initiation to MOD was 14 months (IQR: 3.0-29.5). The most frequent reasons for ST-MOD were gastrointestinal; women had a higher hazard for ST-MOD. Metabolic toxicity was the most frequent reason for LT- MOD, particularly dislipidemia and lipodystrophy. Increased hazard of TF-MOD was observed among those with lower CD4(+) lymphocyte counts (<200 cells/mm(3)). Our results indicate that toxicities can compromise adherence and thus impact future treatment options. This is especially relevant in the context of limited access to second and third line treatment regimens.
AIDS research and human retroviruses 08/2010; 26(8):865-74. · 2.18 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The HIV-1 epidemic in southern Brazil is characterized by the high prevalence of subtype C and CRF31_BC infections but little is known about the population dynamics of these strains over time. We used a total of 82 env and 72 pol HIV-1 subtype C sequences collected from 1991 to 2006 and 47 pol CRF31_BC sequences collected from 1998 to 2006 from Brazilian patients to reconstruct the demographic history of these HIV-1 strains. Estimations of demographic history were performed using a Bayesian Markov Chain Monte Carlo coalescent-based approach as implemented in the BEAST program. Our analyses indicate that subtype C and CRF31_BC epidemics experienced an initial period of fast exponential spread in the southern Brazilian population during the 1980s and early 1990s, but the spreading rate of these epidemics seems to have slowed down since the middle 1990s. The initial mean exponential growth rate of the subtype C epidemic was estimated to be around 0.70-0.90/year, whereas the estimated population growth rate of CRF31_BC was 1.3/year, more than two times higher than that previously described for this CRF. These results suggest for the first time that the growth rate of subtype C and CRF31_BC epidemics has been changing over time in southern Brazil with evidence for a deceleration in recent years. During the expansion phase, the CRF31_BC seems to have spread at a rate much higher than Brazilian parental subtypes B and C.
AIDS research and human retroviruses 11/2009; 25(11):1065-9. · 2.18 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: An extremely rare subset of patients infected with HIV-1 designated as "non-progressing elite controllers" appears to be able to maintain stable CD4(+) T-cell counts and a median plasma viremia below the detection limit of current ultrasensitive assays (<50-80 copies/ml of plasma) for >10 years in the absence of antiretroviral therapy. Lymphocyte subsets (CD4(+), CD8(+)), immune activation markers (HLA-DR(+), CD38(+), Beta-2-microglobulin), and HIV-specific antibody responses were longitudinally examined in four non-progressing elite controllers over more than 5 years. Two control groups of seronegative healthy individuals and untreated patients infected with HIV-1 presenting detectable viremia were also included. None of the non-progressing elite controllers displayed the high T-cell activation levels generally seen in the seropositive individuals, keeping them within the normal range. Three non-progressing elite controllers showed no significant immune system abnormalities when compared to seronegative individuals, displaying a low proportion of HIV-1-specific binding antibodies and low avidity index, similar to those observed for individuals infected recently with HIV-1. One non-progressing elite controller exhibited CD8(+) T-cell counts and beta2-M levels above normal ranges and developed a low but "mature" (high-avidity) HIV-1-specific antibody response. Thus, the non-progressing elite controllers are able to maintain normal T-cell activation levels, which may contribute to prevent, or greatly reduce, the damage of the immune system typically induced by the HIV-1 over time. They are, however, immunologically heterogeneous and very low levels of antigen exposure seem to occur in these patients, sufficient for sustaining a low, but detectable, HIV-1-specific immunity.
Journal of Medical Virology 10/2009; 81(10):1681-90. · 2.82 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: An extremely rare subset of patients infected with HIV-1 designated as “non-progressing elite controllers” appears to be able to maintain stable CD4+ T-cell counts and a median plasma viremia below the detection limit of current ultrasensitive assays (<50–80 copies/ml of plasma) for >10 years in the absence of antiretroviral therapy. Lymphocyte subsets (CD4+, CD8+), immune activation markers (HLA-DR+, CD38+, Beta-2-microglobulin), and HIV-specific antibody responses were longitudinally examined in four non-progressing elite controllers over more than 5 years. Two control groups of seronegative healthy individuals and untreated patients infected with HIV-1 presenting detectable viremia were also included. None of the non-progressing elite controllers displayed the high T-cell activation levels generally seen in the seropositive individuals, keeping them within the normal range. Three non-progressing elite controllers showed no significant immune system abnormalities when compared to seronegative individuals, displaying a low proportion of HIV-1-specific binding antibodies and low avidity index, similar to those observed for individuals infected recently with HIV-1. One non-progressing elite controller exhibited CD8+ T-cell counts and β2-M levels above normal ranges and developed a low but “mature” (high-avidity) HIV-1-specific antibody response. Thus, the non-progressing elite controllers are able to maintain normal T-cell activation levels, which may contribute to prevent, or greatly reduce, the damage of the immune system typically induced by the HIV-1 over time. They are, however, immunologically heterogeneous and very low levels of antigen exposure seem to occur in these patients, sufficient for sustaining a low, but detectable, HIV-1-specific immunity. J. Med. Virol. 81:1681–1690, 2009. © 2009 Wiley-Liss, Inc.
Journal of Medical Virology 08/2009; 81(10):1681 - 1690. · 2.82 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the recombination profiles and evolutionary history of HIV-1 BC recombinants in Southern Brazil, 81 isolates collected in the city of Porto Alegre (Rio Grande do Sul State) from 1998 to 2006 previously subtyped as C (env-gp120/C2V3) were screened in the protease-reverse transcriptase (pr/rt), integrase and gp41 genomic regions. Detailed phylogenetic, bootscan and informative site analyses were performed to trace the subtype classification. The evolutionary rate and divergence time of the Brazilian CRF31_BC epidemic were estimated using a Bayesian Markov Chain Monte Carlo framework. Analysis of the four target regions identified: 43 isolates as "pure" subtype C, 23 as CRF31_BC, and 15 as unique BC recombinant forms (URFs_BC). Recombination breakpoints were mainly localized in the rt gene and 100% of the recombinant samples could be detected analyzing only this region. Most URFs_BC (86.7%) contained small subtype B fragments (<or=160nt) in the rt region and shared one of the recombination breakpoints with CRF31_BC. In conclusion, despite the high co-prevalence of subtypes B and C in Porto Alegre, the diversity of BC recombinant forms circulating in this region was extremely low. Most BC recombinants were CRF31_BC and URFs_BC that appeared to be second generation recombinants derived from CRF31_BC and subtype C strains, confirming the importance of this CRF in this region. The emergence of the CRF31_BC was estimated to be around 1988 (1982-1992).
Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 07/2009; 9(4):474-82. · 3.22 Impact Factor
-
Mark Mirochnick,
Karin Nielsen-Saines,
Jose Henrique Pilotto,
Jorge Pinto,
Eleanor Jiménez, Valdilea G Veloso,
Teresa Parsons,
D Heather Watts,
Jack Moye,
Lynne M Mofenson,
Margaret Camarca,
Yvonne Bryson
[show abstract]
[hide abstract]
ABSTRACT: The optimal neonatal antiretroviral (ARV) regimen for prevention of HIV mother-to-child transmission (MTCT) is unknown for infants born to mothers who receive no ARVs during pregnancy.
As part of a protocol comparing the efficacy of 3 neonatal ARV regimens in preventing HIV-1 MTCT in neonates born to mothers who receive no prenatal treatment with ARVs, we devised a 3-dose nevirapine (NVP) regimen with the goal of maintaining the NVP plasma concentration >100 ng/mL (10 times the in vitro median inhibitory concentration of 10 ng/mL) during the first 2 weeks of life. NVP concentrations were measured in 14 newborns participating in a pharmacokinetics substudy during the second week of life and in single samples from 30 more newborns on day 10 to 14.
The median NVP elimination half-life was 30.2 hours (range: 17.8 to 50.3 hours). The NVP concentration remained greater than the target of 100 ng/mL in all samples collected through day 10 of life. By day 14, more than half of the newborns in the pharmacokinetic substudy had NVP levels <100 ng/mL, although only 1 neonate had no detectable NVP.
Although this regimen failed to meet our 100-ng/mL target, it did maintain detectable NVP concentrations in nearly all newborns through the end of the second week of life and is to be used in the parent efficacy protocol.
JAIDS Journal of Acquired Immune Deficiency Syndromes 03/2008; 47(3):334-7. · 4.43 Impact Factor
-
Gonzalo Bello,
Concepción Casado,
Virginia Sandonis,
Tamara Alvaro-Cifuentes,
Caio A Rodrigues Dos Santos,
Soledad García,
Carmen Rodríguez,
Jorge Del Romero,
José H Pilotto,
Beatriz Grinsztejn, Valdilea G Veloso,
Mariza G Morgado,
Cecilio López-Galíndez
[show abstract]
[hide abstract]
ABSTRACT: The objective of the present study was to determine if natural suppression of plasma viremia below the detection limit of commercial assays (50-80 copies HIV-1 RNA/ml) can contain the HIV-1 evolution. HIV-1 quasispecies complexity in PBMC DNA was assessed in the env gene at two time points in 14 long-term nonprogressors (LTNPs). Sequence changes consistent with viral evolution was found in all patients with a median plasma RNA viral load >100 copies/ml. Evidence of low-level viral evolution was detected in two of four patients with intermittent viremia and a median plasma HIV-1 RNA load of >80 copies/ml. No significant evolution was observed in the three LTNPs with persistent viral suppression below the detection limit. Overall, a significant positive correlation (p < 0.001) was observed between viral evolution and plasma RNA viral load in the LTNPs analyzed. These results suggest that the detection limit of ultrasensitive viremia assays could represent an important threshold below which intrahost HIV-1 evolution does not occur.
AIDS Research and Human Retroviruses 10/2007; 23(10):1242-50. · 2.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: US and Brazilian studies indicate that highly active antiretroviral therapy (HAART) has been effective in reducing morbidity and mortality from HIV/AIDS. Differences exist in the adoption and patterns of antiretroviral drug use and in the incidence of AIDS-defining illness (ADI) between the 2 countries, however, and there has not been a direct comparison of clinical response between Brazil and the United States. We sought to determine if there have been differences in the clinical response to HAART from HIV clinical practices in the United States and Brazil.
We compared 2 similarly designed clinical cohorts from Baltimore, Maryland and Rio de Janeiro, Brazil. Patients who started HAART from 1997 to 2004 were compared for HIV-1 RNA suppression and CD4+ T-lymphocyte count change by 1 year of therapy and for development of an ADI up to 6 years of follow-up. A total of 1368 patients from Baltimore and 1045 patients from Rio de Janeiro were studied.
There was no difference by location in achieving an HIV-1 RNA level <400 copies/mL (46.9% in Rio de Janeiro, 50.8% in Baltimore), in the log change in HIV-1 RNA level (-1.65 log in Rio de Janeiro, - 1.63 log in Baltimore), or in the change in CD4 count (116 cells/mm3 in Rio de Janeiro, 122 cells/mm3 in Baltimore) by 12 months after starting HAART. By Kaplan-Meier analysis and Cox regression adjusted for demographic and clinical prognostic factors, there was no difference by location in development of the first ADI after starting HAART (relative hazard = 1.02; 95% confidence interval: 0.82 to 1.25 for Rio de Janeiro vs. Baltimore). The most commonly occurring ADI in Rio de Janeiro was tuberculosis (27.7% of patients), and the most commonly occurring ADI in Baltimore was esophageal candidiasis (36.8% of patients).
There were only minor differences in clinical response to the use of HAART comparing Rio de Janeiro with Baltimore, despite differences in patterns of antiretroviral drug use and ADI incidence. This analysis indicates that HAART can be similarly effective in treating HIV/AIDS in countries with different economies.
JAIDS Journal of Acquired Immune Deficiency Syndromes 08/2007; 45(5):515-20. · 4.43 Impact Factor
