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Predictors of attrition and immunological failure in HIV- 1 patients on highly active antiretroviral therapy from different healthcare settings in Mozambique
Publication . Palladino, Claudia; Briz, Verónica; Bellón, José María; Bártolo, Inês; Carvalho, Patrícia; Camacho, Ricardo; Munõz-Fernandes, M. Ángeles; Bastos, Rui; Manuel, Rolanda; Casanovas, José; Taveira, Nuno
"In Mozambique, the evaluation of retention in HIV care and ART programmes is limited. To assess rate and predictors of
attrition (no retention in care) and HAART effectiveness in HIV-1 infected patients who pay for medication and laboratory
testing in Mozambique, we conducted a multicenter survey of HIV-1-infected patients who started HAART during 2002–
2006. Cox proportional hazard models were used to assess risk of attrition and of therapy failure. Overall, 142 patients from
16 healthcare centers located in the capital city Maputo were followed-up for 22.2 months (12.1–46.7). The retention rate
was 75%, 48% and 37% after one, two and three years, respectively. Risk of attrition was lower in patients with higher
baseline CD4 count (P = 0.022) and attending healthcare center 1 (HCC1) (P = 0.013). The proportion of individuals with CD4
count #200 cells/mL was 55% (78/142) at baseline and decreased to 6% (3/52) at 36 months. Among the patients with
available VL, 86% (64/74) achieved undetectable VL levels. The rate of immunologic failure was 17.2% (95% CI: 12.6–22.9)
per 100 person-years. Risk of failure was associated to higher baseline CD4 count (P = 0.002), likely reflecting low adherence
levels, and decreased with baseline VL $10,000 copies/mL (P = 0.033). These results suggest that HAART can be effective in
HIV-1 infected patients from Mozambique that pay for their medication and laboratory testing. Further studies are required
to identify the causes for low retention rates in patients with low CD4 counts and to better understand the association
between healthcare setting and attrition rate."
Determinants of highly active antiretroviral therapy duration in HIV-1-infected children and adolescents in Madrid, Spain, from 1996 to 2012
Publication . Palladino, Claudia; Briz, Verónica; Bellón, José María; Climent, Francisco J.; De Ory, Santiago J.; Mellado, María José; Navarro, María Luisa; Ramos, José T.; Taveira, Nuno; De José, María Isabel; Munõz-Fernandes, María Ángeles; CoRISpeS-Madrid Cohort Working Group
"Objectives: To investigate the duration of sequential HAART regimens and predictors of first-line regimen discontinuation
among HIV-1 vertically infected children and adolescents.
Design: Multicentre survey of antiretroviral-naı¨ve patients enrolled in the HIV-Paediatric Cohor,t CoRISpeS-Madrid Cohort,
Spain.
Methods: Patients with a follow-up of $1 month spent on HAART, with available baseline CD4 count and HIV-viral load (VL)
were included. Time spent on sequential HAART regimens was estimated and multivariable regression was used to identify
predictors of time to first-line regimen discontinuation.
Results: 104 patients were followed for a median 8 years after starting HAART among 1996–2012; baseline %CD4 was 21.5
(12.3–34.0)and viral load was 5.1 (4.6–5.6) log10 copies/mL. Patients received a mean of 1.9 regimens. Median time on firstline
HAART (n = 104) was 64.5 months; second HAART (n = 56) 69.8 months; and third HAART (n = 21) 66.5 months. Eleven
(11%) patients were lost to follow-up while on first-line HAART and 54% discontinued (cumulative incidence of 16% and
38% by 1 and 3-year, respectively). The main predictor of first-line regimen discontinuation was suboptimal adherence to
antiretrovirals (AHR: 2.60; 95% CI: 1.44–4.70).
Conclusions: Adherence to therapy was the main determinant of the duration of the first-line HAART regimen in children. It
is important to identify patients at high risk for non-adherence, such as very young children and adolescents, in provide
special care and support to those patients."
HIV-1 Diversity, Transmission Dynamics and Primary Drug Resistance in Angola
Publication . Bártolo, Inês; Zakovic, Susana; Martin, Francisco; Palladino, Claudia; Carvalho, Patrícia; Camacho, Ricardo; Thamm, Sven; Clemente, Sofia; Taveira, Nuno
"Objectives: To assess HIV-1 diversity, transmission dynamics and prevalence of
transmitted drug resistance (TDR) in Angola, five years after ART scale-up.
Methods: Population sequencing of the pol gene was performed on 139 plasma
samples collected in 2009 from drug-naive HIV-1 infected individuals living in
Luanda. HIV-1 subtypes were determined using phylogenetic analysis. Drug
resistance mutations were identified using the Calibrated Population Resistance
Tool (CPR). Transmission networks were determined using phylogenetic analysis
of all Angolan sequences present in the databases. Evolutionary trends were
determined by comparison with a similar survey performed in 2001.
Results: 47.1% of the viruses were pure subtypes (all except B), 47.1% were
recombinants and 5.8% were untypable. The prevalence of subtype A decreased
significantly from 2001 to 2009 (40.0% to 10.8%, P50.0019) while the prevalence
of unique recombinant forms (URFs) increased.2-fold (40.0% to 83.1%,
P,0.0001). The most frequent URFs comprised untypable sequences with
subtypes H (U/H, n57, 10.8%), A (U/A, n56, 9.2%) and G (G/U, n54, 6.2%). Newly
identified U/H recombinants formed a highly supported monophyletic cluster
suggesting a local and common origin. TDR mutation K103N was found in one
(0.7%) patient (1.6% in 2001). Out of the 364 sequences sampled for transmission
network analysis, 130 (35.7%) were part of a transmission network. Forty eight
transmission clusters were identified; the majority (56.3%) comprised sequences
sampled in 2008–2010 in Luanda which is consistent with a locally fuelled
epidemic. Very low genetic distance was found in 27 transmission pairs sampled in
the same year, suggesting recent transmission events.
Conclusions: Transmission of drug resistant strains was still negligible in Luanda
in 2009, five years after the scale-up of ART. The dominance of small and recent
transmission clusters and the emergence of new URFs are consistent with a rising
HIV-1 epidemics mainly driven by heterosexual transmission."
Evaluation of an in-house molecular HIV-1 test to assess mother-to-child HIV-1 transmission in Angola (the APEHC cohort)
Publication . Martin, F.; Palladino, C.; Mateus, R.; Clemente, S.; Gomes, P.; Taveira, N.
"Mother-to-child-transmission (MTCT) rate has decreased sharply in recent years in most of the sub-Saharan Africa, however 220,000 children acquired HIV-1 in 2014. PCR detection of proviral DNA is the most sensitive method for early infant diagnosis (EID) of HIV-1 infection. Commercial kits are available but they have poor sensitivity with divergent non-B subtypes and high costs (≈30€ per test) which limit their use in resource-limited
settings. The HIV-1 epidemic in Angola is driven by highly divergent strains of all group M subtypes, except B, as well as multiple recombinant forms (CRFs and URFs) making EID a challenge in this setting. The aim of this study was to develop and validate a qualitative, inexpensive and sensitive “inhouse” HIV-1 EID assay on heel prick dried blood spots (DBS) from infants of the Hospital da Divina Providência (HDP) in Luanda, Angola and determine the current HIV-1 MTCT rate in the Angolan PErinatal HIV Cohort (APEHC)."
Evolution of the human immunodeficiency virus type 2 envelope in the first years of infection is associated with the dynamics of the neutralizing antibody response
Publication . Rocha, Cheila; Calado, Rita; Borrego, Pedro; Marcelino, José Maria; Bártolo, Inês; Rosado, Lino; Cavaco-Silva, Patrícia; Perpétua, Gomes; Família, Carlos; Quintas, Alexandre; Skar, Helena; Leitner, Thomas; Barroso, Helena; Taveira, Nuno
"Background: Differently from HIV-1, HIV-2 disease progression usually takes decades without antiretroviral therapy
and the majority of HIV-2 infected individuals survive as elite controllers with normal CD4+ T cell counts and low or
undetectable plasma viral load. Neutralizing antibodies (Nabs) are thought to play a central role in HIV-2 evolution
and pathogenesis. However, the dynamic of the Nab response and resulting HIV-2 escape during acute infection
and their impact in HIV-2 evolution and disease progression remain largely unknown. Our objective was to
characterize the Nab response and the molecular and phenotypic evolution of HIV-2 in association with Nab escape
in the first years of infection in two children infected at birth.
Results: CD4+ T cells decreased from about 50% to below 30% in both children in the first five years of infection
and the infecting R5 viruses were replaced by X4 viruses within the same period. With antiretroviral therapy, viral
load in child 1 decreased to undetectable levels and CD4+ T cells recovered to normal levels, which have been
sustained at least until the age of 12. In contrast, viral load increased in child 2 and she progressed to AIDS and
death at age 9. Beginning in the first year of life, child 1 raised high titers of antibodies that neutralized primary R5
isolates more effectively than X4 isolates, both autologous and heterologous. Child 2 raised a weak X4-specific Nab
response that decreased sharply as disease progressed. Rate of evolution, nucleotide and amino acid diversity, and
positive selection, were significantly higher in the envelope of child 1 compared to child 2. Rates of R5-to-X4
tropism switch, of V1 and V3 sequence diversification, and of convergence of V3 to a β-hairpin structure were
related with rate of escape from the neutralizing antibodies.
Conclusion: Our data suggests that the molecular and phenotypic evolution of the human immunodeficiency virus
type 2 envelope are related with the dynamics of the neutralizing antibody response providing further support for
a model in which Nabs play an important role in HIV-2 pathogenesis."
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Funding agency
Fundação para a Ciência e a Tecnologia
Funding programme
3599-PPCDT
Funding Award Number
PTDC/SAU-FAR/115290/2009