RESUMO
BACKGROUND: The World Health Organization (WHO) recommends that HIV treatment scale-up is accompanied by a robust assessment of drug resistance emergence and transmission. The WHO HIV Drug Resistance (HIVDR) monitoring and surveillance strategy includes HIVDR testing in adults both initiating and receiving antiretroviral therapy (ART). Due to limited information about HIVDR in Mozambique, we conducted two nationally representative surveys of adults initiating and receiving first-line ART regimes to better inform the HIV program. METHODS: We carried out a cross-sectional study between March 2017 and December 2019. Adults (older than 15 years) living with HIV (PLHIV) initiating ART or receiving first-line ART for between 9-15 months at 25 health facilities across all eleven provinces in Mozambique were included. Genotypic HIVDR was assessed on dried blood spots (DBS) when viral loads were ≥ 1000 copies/ml. Genotypic resistance for non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) was determined using the Stanford HIV database algorithm 9.5 and calibrated population resistance tool 8.1. RESULTS: Of 828 participants -enrolled, viral load (VL) testing was performed on 408 initiators and 409 ART experienced. Unsuppressed VL was found in 68.1% 419 initiators and 18.8% (77/409) of the ART experienced. Of the 278 initiators and 70 ART experienced who underwent sequencing, 51.7% (144/278) and 75.7% (53/70) were sequenced successfully. Among the new initiators, pretreatment drug resistance (PDR) for NNRTI and PI was found in 16.0% (23/144) and 1.4% (2/144) of the participants, respectively. Acquired drug resistance (ADR) was found in 56.5% (30/53) of the ART-experienced participants of whom 24.5% (13/53) were resistant to both NRTI and NNRTI. CONCLUSION: High rates of PDR and ADR for NNRTI and ADR for NRTI were observed in our study. These findings support the replacement of NNRTIs with dolutegravir (DTG) but high levels of NRTI resistance in highly treatment-experienced individuals still require attention when transitioning to new regimens. Moreover, the study underlines the need for routine VL testing and HIVDR surveillance to improve treatment management strategies.
Assuntos
Fármacos Anti-HIV , Farmacorresistência Viral , Infecções por HIV , HIV-1 , Compostos Heterocíclicos com 3 Anéis , Lamivudina , Oxazinas , Piridonas , Tenofovir , Humanos , Moçambique/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Masculino , Farmacorresistência Viral/genética , Feminino , Adulto , Estudos Transversais , HIV-1/efeitos dos fármacos , HIV-1/genética , Fármacos Anti-HIV/uso terapêutico , Piridonas/uso terapêutico , Pessoa de Meia-Idade , Lamivudina/uso terapêutico , Tenofovir/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Oxazinas/uso terapêutico , Adulto Jovem , Piperazinas/uso terapêutico , Adolescente , Carga Viral/efeitos dos fármacos , GenótipoRESUMO
OBJECTIVE: Evaluate the effect of three multimonth dispensing (3MMD) of antiretroviral therapy (ART) on HIV care retention in southern Mozambique. DESIGN: Retrospective cohort study. METHODS: We analyzed routine health data from people with HIV (PWH) aged 10 years old and older who started ART between January 2018 and March 2021. Individuals were followed until December 2021. Cox proportional-hazards models were used to compare attrition (lost to follow-up, death, and transfer out) between 3MMD and monthly ART dispensing. Results were stratified by time on ART before 3MMD enrolment: 'early enrollers' (<6âmonths on ART) and 'established enrollers' (≥6âmonths on ART), and age groups: adolescents and youth (AYLHIV) (10-24âyears) and adults (≥25âyears). RESULTS: We included 7378 PWH (25% AYLHIV, 75% adults), with 59% and 62% enrolled in 3MMD, respectively. Median follow-up time was 11.3 [interquartile range (IQR): 5.7-21.6] months for AYLHIV and 10.2 (IQR: 4.8-20.9) for adults. Attrition was lower in PWH enrolled in 3MMD compared with monthly ART dispensing, in both established (aHR AYLHIVâ=â0.65; 95% CI: 0.54-0.78 and aHR adultsâ=â0.50; 95% confidence interval (CI): 0.44-0.56) and early enrollers (aHR AYLHIVâ=â0.70; 95% CI: 0.58-0.85 and aHR adultsâ=â0.63; 95% CI: 0.57-0.70). Among individuals in 3MMD, male gender (aHRâ=â1.30; 95% CI: 1.18-1.44) and receiving care in a medium-volume/low-volume healthcare facility (aHRâ=â1.18; 95% CI: 1.03-1.34) increased attrition risk. Conversely, longer ART time before 3MMD enrolment (aHRâ=â0.93; 95% CI: 0.92-0.94 per 1 month increase) and age at least 45âyears (aHRâ=â0.77, 95% CI: 0.67-0.89) reduced risk of attrition. CONCLUSION: 3MMD improves retention in care compared with monthly dispensing among established and early enrollers, although to a lesser extent among the latter.
Assuntos
Infecções por HIV , Retenção nos Cuidados , Humanos , Moçambique , Estudos Retrospectivos , Infecções por HIV/tratamento farmacológico , Masculino , Feminino , Adulto , Adolescente , Adulto Jovem , Criança , Retenção nos Cuidados/estatística & dados numéricos , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , Pessoa de Meia-Idade , Antirretrovirais/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Perda de SeguimentoRESUMO
INTRODUCTION: As COVID-19 continues to spread globally and within Mozambique, its impact among immunosuppressed persons, specifically persons living with HIV (PLHIV), and on the health system is unknown in the country. The 'COVid and hIV' (COVIV) study aims to investigate: (1) the seroprevalence and seroincidence of SARS-CoV-2 among PLHIV and healthcare workers providing HIV services; (2) knowledge, attitudes, practices and perceptions regarding SARS-CoV-2 infection; (3) the pandemic's impact on HIV care continuum outcomes and (4) facility level compliance with national COVID-19 guidelines. METHODS AND ANALYSIS: A multimethod study will be conducted in a maximum of 11 health facilities across Mozambique, comprising four components: (1) a cohort study among PLHIV and healthcare workers providing HIV services to determine the seroprevalence and seroincidence of SARS-CoV-2, (2) a structured survey to assess knowledge, attitudes, perceptions and practices regarding COVID-19 disease, (3) analysis of aggregated patient data to evaluate retention in HIV services among PLHIV, (4) an assessment of facility implementation of infection prevention and control measures. ETHICS AND DISSEMINATION: Ethical approval was obtained from the National Health Bioethics Committee, and institutional review boards of implementing partners. Study findings will be discussed with local and national health authorities and key stakeholders and will be disseminated in clinical and scientific forums. TRIAL REGISTRATION NUMBER: NCT05022407.
Assuntos
COVID-19 , Infecções por HIV , Humanos , Estudos de Coortes , COVID-19/epidemiologia , Pessoal de Saúde , Infecções por HIV/epidemiologia , Infecções por HIV/tratamento farmacológico , Moçambique/epidemiologia , Estudos Prospectivos , SARS-CoV-2 , Estudos SoroepidemiológicosRESUMO
HIV drug resistance (HIVDR) can become a public health concern, especially in low- and middle-income countries where genotypic testing for people initiating antiretroviral therapy (ART) is not available. For first-line regimens to remain effective, levels of transmitted drug resistance (TDR) need to be monitored over time. To determine the temporal trends of TDR in Mozambique, a search for studies in PubMed and sequences in GenBank was performed. Only studies covering the pol region that described HIVDR and genetic diversity from treatment naïve patients were included. A dataset from seven published studies and one novel unpublished study conducted between 1999 and 2018 were included. The Calibrated Population Resistance tool (CPR) and REGA HIV-1 Subtyping Tool version 3 for sequences pooled by sampling year were used to determine resistance mutations and subtypes, respectively. The prevalence of HIVDR amongst treatment-naïve individuals increased over time, reaching 14.4% in 2018. The increase was most prominent for non-nucleoside reverse transcriptase inhibitors (NNRTIs), reaching 12.7% in 2018. Subtype C was predominant in all regions, but a higher genetic variability (19% non-subtype C) was observed in the north region of Mozambique. These findings confirm a higher diversity of HIV in the north of the country and an increased prevalence of NNRTI resistance among treatment naïve individuals over time.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Soropositividade para HIV , HIV-1 , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , HIV-1/genética , Humanos , Epidemiologia Molecular , Moçambique/epidemiologia , Mutação , Prevalência , Inibidores da Transcriptase Reversa/farmacologiaRESUMO
BACKGROUND: Virologic failure (VF) is highly prevalent in sub-Saharan African children on antiretroviral therapy (ART) and is often associated with human immunodeficiency virus drug resistance (DR). Most children still lack access to routine viral load (VL) monitoring for early identification of treatment failure, with implications for the efficacy of second-line ART. METHODS: Children aged 1 to 14 years on ART for ≥12 months at 6 public facilities in Maputo, Mozambique were consecutively enrolled after informed consent. Chart review and caregiver interviews were conducted. VL testing was performed, and specimens with ≥1000 copies/mL were genotyped. RESULTS: Of the 715 children included, the mean age was 103 months, 85.8% had no immunosuppression, 73.1% were taking stavudine/lamivudine/nevirapine, and 20.1% had a history prevention of mother-to-child transmission exposure. The mean time on ART was 60.0 months. VF was present in 259 patients (36.3%); 248 (95.8%) specimens were genotyped, and DR mutations were found in 238 (96.0%). Severe immunosuppression and nutritional decline were associated with DR. M184V and Y181C were the most common mutations. In the 238 patients with DR, standard second-line ART would have 0, 1, 2, and 3 effective antiretrovirals in 1 (0.4%), 74 (31.1%), 150 (63.0%), and 13 (5.5%) patients, respectively. CONCLUSION: This cohort had high rates of VF and DR with frequent compromise of second-line ART. There is urgent need to scale-up VL monitoring and heat-stable protease inhibitor formulations or integrase inhibitorsfor a more a durable first-line regimen that can feasibly be implemented in developing settings.
Assuntos
Antirretrovirais/uso terapêutico , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , Lamivudina/uso terapêutico , Nevirapina/uso terapêutico , Estavudina/uso terapêutico , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , HIV/efeitos dos fármacos , Infecções por HIV/virologia , Humanos , Lactente , Lamivudina/farmacologia , Masculino , Moçambique , Nevirapina/farmacologia , Estavudina/farmacologia , Falha de Tratamento , Carga ViralRESUMO
Quantitative plasma viral load (VL) at 1000 copies /mL was recommended as the threshold to confirm antiretroviral therapy (ART) failure by the World Health Organization (WHO). Because of ongoing challenges of using plasma for VL testing in resource-limited settings (RLS), especially for children, this study collected 717 DBS and paired plasma samples from children receiving ART ≥1 year in Mozambique and compared the performance of DBS using Abbott's VL test with a paired plasma sample using Roche's VL test. At a cut-off of 1000 copies/mL, sensitivity of DBS using Abbott DBS VL test was 79.9%, better than 71.0% and 63.9% at 3000 and 5000 copies/mL, respectively. Specificities were 97.6%, 98.8%, 99.3% at 1000, 3000, and 5000 copies/mL, respectively. The Kappa value at 1000 copies/mL, 0.80 (95% CI: 0.73, 0.87), was higher than 0.73 (95% CI: 0.66, 0.80) and 0.66 (95% CI: 0.59, 0.73) at 3000, 5000 copies/mL, respectively, also indicating better agreement. The mean difference between the DBS and plasma VL tests with 95% limits of agreement by Bland-Altman was 0.311 (-0.908, 1.530). Among 73 children with plasma VL between 1000 to 5000 copies/mL, the DBS results were undetectable in 53 at the 1000 copies/mL threshold. While one DBS sample in the Abbott DBS VL test may be an alternative method to confirm ART failure at 1000 copies/mL threshold when a plasma sample is not an option for treatment monitoring, because of sensitivity concerns between 1,000 and 5,000 copies/ml, two DBS samples may be preferred accompanied by careful patient monitoring and repeat testing.
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Infecções por HIV/terapia , HIV-1/fisiologia , Infecções por HIV/virologia , Sensibilidade e Especificidade , HIV-1/imunologia , Falha de Tratamento , Carga Viral , Terapia Antirretroviral de Alta Atividade/métodos , MoçambiqueRESUMO
Quantitative plasma viral load (VL) at 1000 copies /mL was recommended as the threshold to confirm antiretroviral therapy (ART) failure by the World Health Organization (WHO). Because of ongoing challenges of using plasma for VL testing in resource-limited settings (RLS), especially for children, this study collected 717 DBS and paired plasma samples from children receiving ART ≥1 year in Mozambique and compared the performance of DBS using Abbott's VL test with a paired plasma sample using Roche's VL test. At a cut-off of 1000 copies/mL, sensitivity of DBS using Abbott DBS VL test was 79.9%, better than 71.0% and 63.9% at 3000 and 5000 copies/mL, respectively. Specificities were 97.6%, 98.8%, 99.3% at 1000, 3000, and 5000 copies/mL, respectively. The Kappa value at 1000 copies/mL, 0.80 (95% CI: 0.73, 0.87), was higher than 0.73 (95% CI: 0.66, 0.80) and 0.66 (95% CI: 0.59, 0.73) at 3000, 5000 copies/mL, respectively, also indicating better agreement. The mean difference between the DBS and plasma VL tests with 95% limits of agreement by Bland-Altman was 0.311 (-0.908, 1.530). Among 73 children with plasma VL between 1000 to 5000 copies/mL, the DBS results were undetectable in 53 at the 1000 copies/mL threshold. While one DBS sample in the Abbott DBS VL test may be an alternative method to confirm ART failure at 1000 copies/mL threshold when a plasma sample is not an option for treatment monitoring, because of sensitivity concerns between 1,000 and 5,000 copies/ml, two DBS samples may be preferred accompanied by careful patient monitoring and repeat testing.
Assuntos
Antirretrovirais/uso terapêutico , Teste em Amostras de Sangue Seco/métodos , Infecções por HIV/tratamento farmacológico , HIV-1/fisiologia , Adolescente , Terapia Antirretroviral de Alta Atividade/métodos , Criança , Pré-Escolar , Estudos Transversais , Feminino , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Humanos , Lactente , Masculino , Moçambique , Sensibilidade e Especificidade , Falha de Tratamento , Carga ViralRESUMO
BACKGROUND: 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). METHODOLOGY/PRINCIPAL FINDINGS: 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%). CONCLUSIONS: 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.
Assuntos
Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Adulto , Instituições de Assistência Ambulatorial , Contagem de Linfócito CD4 , Farmacorresistência Viral/genética , Feminino , Genótipo , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/genética , HIV-1/fisiologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Masculino , Moçambique/epidemiologia , Mutação , Prevalência , Fatores de Tempo , Falha de Tratamento , Carga Viral/efeitos dos fármacos , Carga Viral/genéticaRESUMO
Background: 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). Methodology/principal findings: 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%). Conclusions: 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.
Assuntos
Humanos , Animais , Masculino , Feminino , Adulto , Infecções por HIV/reabilitação , HIV-1/efeitos dos fármacos , Terapia Antirretroviral de Alta Atividade , Antirretrovirais/uso terapêutico , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Prevalência , HIV-1/fisiologia , HIV-1/genética , Falha de Tratamento , Contagem de Linfócito CD4 , Carga Viral/efeitos da radiação , Carga Viral/genética , Farmacorresistência Viral , Farmacorresistência Viral/genética , Interações Hospedeiro-Patógeno , Assistência Ambulatorial , Genótipo , MutaçãoRESUMO
The HIV-1 subtype C has been substituting the subtype B population in southern Brazil. This phenomenon has been previously described in other countries, suggesting that subtype C may possess greater fitness than other subtypes. The HIV-1 long-terminal repeat (LTR) is an important regulatory region critical for the viral life cycle. Sequence insertions immediately upstream of the viral enhancer are known as the most frequent naturally occurring length polimorphisms (MFNLP). Previous reports demonstrated that the MFNLP could lead to the duplication of transcription factor binding sites (TFBS) enhancing the activity of the HIV-1 subtype C LTR. Here, we amplified and sequenced the LTR obtained from proviral DNA samples collected from patients infected with subtype C from the Southern Region of Brazil (naïve or treatment failure) and Mozambique (only naïve). We confirm the presence of different types of insertions in the LTR sequences of both the countries leading to the creation of additional TFBS. In the Brazilian clinical samples, the frequency of the sequence insertion was significantly higher in subjects experiencing treatment failure than in antiretroviral naïve patients.
Assuntos
Sítios de Ligação , Variação Genética , Genótipo , Infecções por HIV/virologia , Repetição Terminal Longa de HIV/genética , HIV-1/genética , Fatores de Transcrição/metabolismo , Sequência de Bases , Brasil , Regulação Viral da Expressão Gênica , Humanos , Dados de Sequência Molecular , Moçambique , Regiões Promotoras Genéticas , Transcrição GênicaRESUMO
Enfuvirtide was the first fusion inhibitor approved by the Food and Drug Administration (FDA) in 2003 for HIV-1 infection in treatment-experienced patient. It is the first approved antiviral agent to attack the HIV life cycle in its early stages. For HIV fusion to occur, the HR1 and HR2 domains in the gp41 region need to interact. Enfuvirtide is a synthetic peptide that corresponds to 36 amino acids of the HR2, which competitively binds to HR1 inhibiting the interaction with the HR2 domain thus preventing fusogenic conformation and inhibiting viral entry into host cells. Resistance to enfuvirtide is conferred by mutations occurring in the HR1 region involving residues 36-45. Mozambique, a sub-Saharan country, with an HIV prevalence of 11.5%, provides first line and second line antiretroviral therapy (ART)-based treatment. In poor resource settings such as Mozambique the lack of adequate infrastructures, the high costs of viral load tests, and the availability of salvage treatment have hindered the intended objective of monitoring HIV treatment, suggesting an important concern regarding the development of drug resistance. The general aim of this study was to evaluate naturally occurring polymorphisms and resistance-associated mutations in the gp41 region of HIV-1 isolates from Mozambique. The study included 78 patients naive to ARV treatment and 28 patients failing first line regimen recruited from Centro de Saúde Alto-Maé situated in Maputo. The gp41 gene from 103 patients was sequenced and resistance-associated mutations for enfuvirtide were screened. Subtype analysis revealed that 96% of the sequences were classified as subtype C, 2% as subtype G, 1% as subtype A1, and the other 1% as a mosaic form composed of A1/C. No enfuvirtide resistance-associated mutations in HR1 of gp41 were detected. The major polymorphisms in the HR1 were N42S, L54M, A67T, and V72I. This study suggests that this new class of antiviral drug may be effective as a salvage therapy in patients failing first line regimens in Mozambique. However, further phenotypic studies are required to determine the clinical relevance of the polymorphisms detected in this study.
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Adulto , Pessoa de Meia-Idade , Polimorfismo Genético , Proteína gp41 do Envelope de HIV/genética , Infecções por HIV/virologia , HIV-1/genética , Fragmentos de Peptídeos , Filogenia , RNA Viral , Dados de Sequência Molecular , Análise por Conglomerados , Alinhamento de Sequência , Sequência de Aminoácidos , HIV-1/classificação , Falha de Tratamento , Análise de Sequência de DNA , Fármacos Anti-HIV , Mutação de Sentido Incorreto , Farmacorresistência Viral , Enfuvirtida , Genótipo , MoçambiqueRESUMO
Enfuvirtide was the first fusion inhibitor approved by the Food and Drug Administration (FDA) in 2003 for HIV-1 infection in treatment-experienced patient. It is the first approved antiviral agent to attack the HIV life cycle in its early stages. For HIV fusion to occur, the HR1 and HR2 domains in the gp41 region need to interact. Enfuvirtide is a synthetic peptide that corresponds to 36 amino acids of the HR2, which competitively binds to HR1 inhibiting the interaction with the HR2 domain thus preventing fusogenic conformation and inhibiting viral entry into host cells. Resistance to enfuvirtide is conferred by mutations occurring in the HR1 region involving residues 36-45. Mozambique, a sub-Saharan country, with an HIV prevalence of 11.5%, provides first line and second line antiretroviral therapy (ART)-based treatment. In poor resource settings such as Mozambique the lack of adequate infrastructures, the high costs of viral load tests, and the availability of salvage treatment have hindered the intended objective of monitoring HIV treatment, suggesting an important concern regarding the development of drug resistance. The general aim of this study was to evaluate naturally occurring polymorphisms and resistance-associated mutations in the gp41 region of HIV-1 isolates from Mozambique. The study included 78 patients naive to ARV treatment and 28 patients failing first line regimen recruited from Centro de Saúde Alto-Maé situated in Maputo. The gp41 gene from 103 patients was sequenced and resistance-associated mutations for enfuvirtide were screened. Subtype analysis revealed that 96% of the sequences were classified as subtype C, 2% as subtype G, 1% as subtype A1, and the other 1% as a mosaic form composed of A1/C. No enfuvirtide resistance-associated mutations in HR1 of gp41 were detected. The major polymorphisms in the HR1 were N42S, L54M, A67T, and V72I. This study suggests that this new class of antiviral drug may be effective as a salvage therapy in patients failing first line regimens in Mozambique. However, further phenotypic studies are required to determine the clinical relevance of the polymorphisms detected in this study.
Assuntos
Proteína gp41 do Envelope de HIV/genética , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , Polimorfismo Genético , Adolescente , Adulto , Sequência de Aminoácidos , Fármacos Anti-HIV/uso terapêutico , Criança , Pré-Escolar , Análise por Conglomerados , Farmacorresistência Viral , Enfuvirtida , Feminino , Genótipo , Proteína gp41 do Envelope de HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Moçambique , Mutação de Sentido Incorreto , Fragmentos de Peptídeos/uso terapêutico , Filogenia , RNA Viral/genética , Alinhamento de Sequência , Análise de Sequência de DNA , Falha de Tratamento , Adulto JovemRESUMO
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral , Genótipo , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Adolescente , Adulto , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Farmacorresistência Viral/genética , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , HIV-1/classificação , Humanos , Masculino , Moçambique/epidemiologia , Mutação , Filogenia , Gravidez , Adulto JovemRESUMO
We performed a comparative analysis between Roche Amplicor HIV-1 DNA test and CAPTAQ assay for the detection of HIV in 830 dried blood spot (DBS) pediatric samples collected in Mozambique. Our results demonstrated no statistical difference between these assays. The CAPTAQ assay approached nearly 100% repeatability/accuracy. The increased throughput of testing with minimal operator interference in performing the CAPTAQ assay clearly demonstrated that this method is an improvement over the Roche Amplicor HIV-1 DNA test, version 1.5.
Assuntos
Teste em Amostras de Sangue Seco/métodos , Infecções por HIV/diagnóstico , HIV-1/genética , Infecções por HIV/sangue , Humanos , Lactente , Técnicas de Diagnóstico Molecular , Moçambique , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Human T-Cell Lymphotropic Virus Type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It has been estimated that 10-20 million people are infected worldwide, but no successful treatment is available. Recently, the epidemiology of this virus was addressed in blood donors from Maputo, showing rates from 0.9 to 1.2%. However, the origin and impact of HTLV endemic in this population is unknown. OBJECTIVE: To assess the HTLV-1 molecular epidemiology in Mozambique and to investigate their relationship with HTLV-1 lineages circulating worldwide. METHODS: Blood donors and HIV patients were screened for HTLV antibodies by using enzyme immunoassay, followed by Western Blot. PCR and sequencing of HTLV-1 LTR region were applied and genetic HTLV-1 subtypes were assigned by the neighbor-joining method. The mean genetic distance of Mozambican HTLV-1 lineages among the genetic clusters were determined. Human mitochondrial (mt) DNA analysis was performed and individuals classified in mtDNA haplogroups. RESULTS: LTR HTLV-1 analysis demonstrated that all isolates belong to the Transcontinental subgroup of the Cosmopolitan subtype. Mozambican HTLV-1 sequences had a high inter-strain genetic distance, reflecting in three major clusters. One cluster is associated with the South Africa sequences, one is related with Middle East and India strains and the third is a specific Mozambican cluster. Interestingly, 83.3% of HIV/HTLV-1 co-infection was observed in the Mozambican cluster. The human mtDNA haplotypes revealed that all belong to the African macrohaplogroup L with frequencies representatives of the country. CONCLUSIONS: The Mozambican HTLV-1 genetic diversity detected in this study reveals that although the strains belong to the most prevalent and worldwide distributed Transcontinental subgroup of the Cosmopolitan subtype, there is a high HTLV diversity that could be correlated with at least 3 different HTLV-1 introductions in the country. The significant rate of HTLV-1a/HIV-1C co-infection, particularly in the Mozambican cluster, has important implications for the controls programs of both viruses.
Assuntos
Infecções por HTLV-I/epidemiologia , Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/classificação , Vírus Linfotrópico T Tipo 1 Humano/genética , Doadores de Sangue , Western Blotting , Análise por Conglomerados , Genótipo , Infecções por HIV/complicações , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Humanos , Técnicas Imunoenzimáticas , Epidemiologia Molecular , Dados de Sequência Molecular , Moçambique/epidemiologia , Filogenia , Reação em Cadeia da Polimerase , RNA Viral/genética , Análise de Sequência de DNARESUMO
BACKGROUND: Recent data have shown that HTLV-1 is prevalent among HIV positive patients in Mozambique, although the impact of HTLV-1 infection on HIV disease progression remains controversial. Our aim was to determine the phenotypic profile of T lymphocytes subsets among Mozambican patients co-infected by HIV and HTLV-1. METHODS: We enrolled 29 patients co-infected by HTLV-1 and HIV (co-infected), 59 patients mono-infected by HIV (HIV) and 16 healthy controls (HC), respectively.For phenotypic analysis, cells were stained with the following fluorochrome-labeled anti-human monoclonal antibodies CD4-APC, CD8-PerCP, CD25-PE, CD62L-FITC, CD45RA-FITC. CD45RO-PE, CD38-PE; being analysed by four-colour flow cytometry. RESULTS: We initially found that CD4+ T cell counts were significantly higher in co-infected, as compared to HIV groups. Moreover, CD4+ T Lymphocytes from co-infected patients presented significantly higher levels of CD45RO and CD25, but lower levels of CD45RA and CD62L, strongly indicating that CD4+ T cells are more activated under HTLV-1 plus HIV co-infection. CONCLUSION: Our data indicate that HTLV-1/HIV co-infected patients progress with higher CD4+ T cell counts and higher levels of activation markers. In this context, it is conceivable that in co-infected individuals, these higher levels of activation may account for a faster progression to AIDS.
Assuntos
Síndrome da Imunodeficiência Adquirida/imunologia , Síndrome da Imunodeficiência Adquirida/virologia , Progressão da Doença , HIV-1/fisiologia , Infecções por HTLV-I/imunologia , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Síndrome da Imunodeficiência Adquirida/patologia , Adulto , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Estudos de Casos e Controles , Feminino , Citometria de Fluxo , Anticorpos Anti-HIV/sangue , HIV-1/imunologia , Anticorpos Anti-HTLV-I/sangue , Infecções por HTLV-I/patologia , Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , MoçambiqueRESUMO
BACKGROUND: Resistant virus may be selected by sub-optimal control of HIV-1 replication during antiretroviral treatment. The incidence and profile of resistance in children receiving World Health Organization-recommended treatment remains to be evaluated on a large scale. GOALS: Assessment of the frequency and profile of resistant virus in HIV-1-infected children, treated for at least 6 months with stavudine/zidovudine + lamivudine + nevirapine and presenting virological failure in a large access program in Maputo, Mozambique. RESULTS: Cross-sectional evaluation of plasma HIV-1 viral load (VL) in 495 evaluable children among 512 treated for at least 6 months showed that 360 (72.7%) had a VL of <50 copies/mL of HIV-1 RNA. Genotypic resistance tests were performed in the 84 available samples from the 135 treated children with VL > or = 50 copies/mL: 92% of the viruses were resistant to lamivudine and/or nevirapine, and 15% were resistant to stavudine. Twenty children (24%) harbored virus with a extended spectrum of cross-resistance defined as resistance to the 3 drugs of the combination received by the child and/or at least 1 resistance to a drug to which the child had never been exposed (abacavir: 5%, tenofovir: 6%, didanosine: 3.5% and the new generation non nucleoside inhibitor, etravirine: 6%). The only factor identified by multivariate analysis as being associated with this extended resistance profile was the duration of treatment (aOR: 6.67 [95% CI: 1.24-35.93], P = 0.015 for treatment >24 months) with a per month increase of 1.09 (1.02-1.16) P = 0.007. CONCLUSIONS: Residual viral replication in children receiving stavudine/zidovudine + lamivudine + nevirapine treatment is associated with a time-dependent risk of acquiring cross-resistance, including resistance to drugs currently used for second-line treatment and also to the new generation of non nucleoside reverse transcriptase inhibitors.