Immunological monitoring of HIV disease in resource-poor settings

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Submitted by Sandra Infurna ([email protected]) on 2019-05-16T17:25:53Z No. of bitstreams: 1 WilsonSavino_PauloBuss_etal_IOC_2008.pdf: 146162 bytes, checksum: e28bf04b75642c25c4ff3d1837420abe (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-05-16T17:33:43Z (GMT) No. of bitstreams: 1 WilsonSavino_PauloBuss_etal_IOC_2008.pdf: 146162 bytes, checksum: e28bf04b75642c25c4ff3d1837420abe (MD5)Made available in DSpace on 2019-05-16T17:33:43Z (GMT). No. of bitstreams: 1 WilsonSavino_PauloBuss_etal_IOC_2008.pdf: 146162 bytes, checksum: e28bf04b75642c25c4ff3d1837420abe (MD5) Previous issue date: 2008Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ. Brasil.National Institute of Health. Maputo, Mozambique.National Institute of Health. Maputo, Mozambique.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ. Brasil

Evolution of primary HIV drug resistance in a subtype C dominated epidemic in Mozambique.

In Mozambique, highly active antiretroviral treatment (HAART) was introduced in 2004 followed by decentralization and expansion, resulting in a more than 20-fold increase in coverage by 2009. Implementation of HIV drug resistance threshold surveys (HIVDR-TS) is crucial in order to monitor the emergence of transmitted viral resistance, and to produce evidence-based recommendations to support antiretroviral (ARV) policy in Mozambique.World Health Organization (WHO) methodology was used to evaluate transmitted drug resistance (TDR) in newly diagnosed HIV-1 infected pregnant women attending ante-natal clinics in Maputo and Beira to non-nucleoside reverse transcriptase inhibitors (NNRTI), nucleoside reverse transcriptase inhibitors (NRTI) and protease inhibitors (PI). Subtypes were assigned using REGA HIV-1 subtyping tool and phylogenetic trees constructed using MEGA version 5.Although mutations associated with resistance to all three drug were detected in these surveys, transmitted resistance was analyzed and classified as <5% in Maputo in both surveys for all three drug classes. Transmitted resistance to NNRTI in Beira in 2009 was classified between 5-15%, an increase from 2007 when no NNRTI mutations were found. All sequences clustered with subtype C.Our results show that the epidemic is dominated by subtype C, where the first-line option based on two NRTI and one NNRTI is still effective for treatment of HIV infection, but intermediate levels of TDR found in Beira reinforce the need for constant evaluation with continuing treatment expansion in Mozambique

Prevalence of HIV-1 RAM and aminoacid substitutions at codon positions known to be associated to resistance to NRTI´s (a) and NNRTI´s (b) in 68 sequences from naïve subjects, according to IAS-USA 2011 list.

<p>Prevalence of HIV-1 RAM and aminoacid substitutions at codon positions known to be associated to resistance to NRTI´s (a) and NNRTI´s (b) in 68 sequences from naïve subjects, according to IAS-USA 2011 list.</p

Prediction of drug viral susceptibility to nucleoside reverse transcriptase inhibitors (NRTI) and nonnucleoside reverse transcriptase inhibitors (NNRTI), of sequences harboring at least one RAM from all groups (n = 17).

<p>Drug susceptibility predicted using Stanford HIVdb (Version 6.2.0).</p

Imuno/virological and drug resistance profile of subjects from differentgroups failing first-line HAART.

<p>* Sample with load viral below of 5000 copies/ml, and with resistance mutations.</p><p>Imuno/virological and drug resistance profile of subjects from differentgroups failing first-line HAART.</p

Trends in Prevalence of HIV-1 Drug Resistance in a Public Clinic in Maputo, Mozambique

<div><p>Background</p><p>An observational study was conducted in Maputo, Mozambique, to investigate trends in prevalence of HIV drug resistance (HIVDR) in antiretroviral (ART) naïve subjects initiating highly active antiretroviral treatment (HAART).</p><p>Methodology/Principal Findings</p><p>To evaluate the pattern of drug resistance mutations (DRMs) found in adults on ART failing first-line HAART [patients with detectable viral load (VL)]. Untreated subjects [Group 1 (G1; n=99)] and 274 treated subjects with variable length of exposure to ARV´s [6–12 months, Group 2 (G2;n=93); 12-24 months, Group 3 (G3;n=81); >24 months (G4;n=100)] were enrolled. Virological and immunological failure (VF and IF) were measured based on viral load (VL) and T lymphocyte CD4+ cells (TCD4+) count and genotypic resistance was also performed. Major subtype found was C (untreated: n=66, 97,06%; treated: n=36, 91.7%). Maximum virological suppression was observed in G3, and significant differences intragroup were observed between VF and IF in G4 (p=0.022). Intergroup differences were observed between G3 and G4 for VF (p=0.023) and IF between G2 and G4 (p=0.0018). Viral suppression (<50 copies/ml) ranged from 84.9% to 90.1%, and concordant VL and DRM ranged from 25% to 57%. WHO cut-off for determining VF as given by 2010 guidelines (>5000 copies/ml) identified 50% of subjects carrying DRM compared to 100% when lower VL cut-off was used (<50 copies/ml). Length of exposure to ARVs was directly proportional to the complexity of DRM patterns. In Mozambique, VL suppression was achieved in 76% of individuals after 24 months on HAART. This is in agreement with WHO target for HIVDR prevention target (70%).</p><p>Conclusions</p><p>We demonstrated that the best way to determine therapeutic failure is VL compared to CD4 counts. The rationalized use of VL testing is needed to ensure timely detection of treatment failures preventing the occurrence of TDR and new infections.</p></div

Prevalence of virological and immunological failure in HAART exposed groups (2 to 4).

<p>The lines above bars represent significant differences (p<0.05) calculated by <i>Mann-Whitney</i> test. ***Significant differences in IF between G3 and G4; **Significant differences in VF between G3 and G4; * Significant differences between IF and VF in G4.</p

HAART service coverage at included antenatal care sites in Mozambique.

<p>HAART service coverage at included antenatal care sites in Mozambique.</p

Phylogenetic tree depicting HIV sequences from Maputo analyzed in 2009 TDR threshold survey.

<p>Tree was constructed bases on complete sequences of protease and part of RT gene (1.317 bp), using Kimura 2-parameter (K2P) model of base substitution with bootstrap analysis (100 replications) in MEGA 5.05. Nomenclature of samples herein characterized is as follows: MZ (country) and year of sequencing-patient code-region of isolation [CID: Jose Macamo Health Center and 1° de Junho Health Center]. Tree includes sequences of the HIV-1 subtypes inferred through REGA (empty circles) along with previously described subtype C in the region, India and Brazil (full circles), other subtypes (other full shapes) and outlier group CPZ, obtained from Los Alamos HIV Sequence Database Subtype Reference Alignments (http: //<a href="http://www.hiv.lanl.gov/content/index" target="_blank">www.hiv.lanl.gov/content/index</a>).</p