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1.
J Int AIDS Soc ; 27(2): e26216, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38332525

RESUMO

INTRODUCTION: Dolutegravir (DTG) is widely used for antiretroviral therapy (ART). We compared weight and blood pressure trends and examined the association between high blood pressure and weight gain among people living with HIV (PLHIV) switching to or starting DTG-based, efavirenz (EFV)-based and ritonavir-boosted atazanavir (ATV/r)-based ART in Zimbabwe. METHODS: PLHIV aged 18 years or older who started or switched to DTG, EFV or ATV/r-based ART between January 2004 and June 2022 at Newlands Clinic in Harare, Zimbabwe, were eligible. Weight was measured at all visits (Seca floor scales); blood pressure only at clinician-led visits (Omron M2 sphygmomanometer). We used Bayesian additive models to estimate trends in weight gain and the proportion with high blood pressure (systolic >140 mmHg or diastolic >90 mmHg) in the first 2 years after starting or switching the regimen. Finally, we examined whether trends in the proportion with high blood pressure were related to weight change. RESULTS: We analysed 99,969 weight and 35,449 blood pressure records from 9487 adults (DTG: 4593; EFV: 3599; ATV/r: 1295). At 24 months after starting or switching to DTG, estimated median weight gains were 4.54 kg (90% credibility interval 3.88-5.28 kg) in women and 3.71 kg (3.07-4.45 kg) in men, around twice that observed for ATV/r and over four-times the gain observed for EFV. Prevalence of high blood pressure among PLHIV receiving DTG-based ART increased from around 5% at baseline to over 20% at 24 months, with no change in PLHIV receiving EFV- or ATV/r-based ART. High blood pressure in PLHIV switching to DTG was associated with weight gain, with stronger increases in the proportion with high blood pressure for larger weight gains. CONCLUSIONS: Among PLHIV starting ART or switching to a new regimen, DTG-based ART was associated with larger weight gains and a substantial increase in the prevalence of high blood pressure. Routine weight and blood pressure measurement and interventions to lower blood pressure could benefit PLHIV on DTG-based ART. Further studies are needed to elucidate the mechanisms and reversibility of these changes after discontinuation of DTG.


Assuntos
Alcinos , Fármacos Anti-HIV , Ciclopropanos , Infecções por HIV , Hipertensão , Oxazinas , Piperazinas , Piridonas , Adulto , Masculino , Humanos , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Estudos Longitudinais , Sulfato de Atazanavir/efeitos adversos , Pressão Sanguínea , Zimbábue/epidemiologia , Teorema de Bayes , Benzoxazinas/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Aumento de Peso , Peso Corporal , Fármacos Anti-HIV/efeitos adversos
2.
PLoS One ; 19(2): e0293162, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38394297

RESUMO

There are few data from sub-Saharan Africa on the virological outcomes associated with second-line ART based on protease inhibitors or dolutegravir (DTG). We compared viral load (VL) suppression among people living with HIV (PLWH) on atazanavir (ATV/r)- or DTG-based second-line ART with PLWH on efavirenz (EFV)-based first-line ART. We analyzed data from the electronic medical records system of Newlands Clinic in Harare, Zimbabwe. We included individuals aged ≥12 years when commencing first-line EFV-based ART or switching to second-line DTG- or ATV/r-based ART with ≥24 weeks follow-up after start or switch. We computed suppression rates (HIV VL <50 copies/mL) at weeks 12, 24, 48, 72, and 96 and estimated the probability of VL suppression by treatment regimen, time since start/switch of ART, sex, age, and CD4 cell count (at start/switch) using logistic regression in a Bayesian framework. We included 7013 VL measurements of 1049 PLWH (61% female) initiating first-line ART and 1114 PLWH (58% female) switching to second-line ART. Among those switching, 872 (78.3%) were switched to ATV/r and 242 (21.7%) to DTG. VL suppression was lower in second-line ART than first-line ART, except at week 12, when those on DTG showed higher suppression than those on EFV (aOR 2.10, 95%-credible interval [CrI] 1.48-3.00) and ATV/r-based regimens (aOR 1.87, 95%-CrI 1.32-2.71). For follow-up times exceeding 24 weeks however, first-line participants demonstrated significantly higher VL suppression than second-line, with no evidence for a difference between DTG and ATV/r. Notably, from week 48 onward, VL suppression seemed to stabilize across all regimen groups, with an estimated 89.1% (95% CrI 86.9-90.9%) VL suppression in EFV, 74.5% (95%-CrI 68.0-80.7%) in DTG, and 72.9% (95%-CrI 69.5-76.1%) in ATV/r at week 48, showing little change for longer follow-up times. Virologic monitoring and adherence support remain essential even in the DTG era to prevent second-line treatment failure in settings with limited treatment options.


Assuntos
Alcinos , Fármacos Anti-HIV , Ciclopropanos , Infecções por HIV , Compostos Heterocíclicos com 3 Anéis , Oxazinas , Piperazinas , Piridonas , Humanos , Feminino , Masculino , Fármacos Anti-HIV/uso terapêutico , Sulfato de Atazanavir/uso terapêutico , Estudos Longitudinais , Zimbábue , Teorema de Bayes , Infecções por HIV/tratamento farmacológico , Benzoxazinas/uso terapêutico , Carga Viral
3.
AIDS ; 38(5): 689-696, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38227596

RESUMO

OBJECTIVE: Dolutegravir (DTG)-based antiretroviral therapy (ART) is being scaled up in Africa. However, clinical experience with DTG and patterns of HIV drug resistance (HIVDR) are sparse in Zimbabwe. We assessed virological, weight, and HIVDR outcomes among individuals initiating on a DTG-based ART. DESIGN: We conducted a prospective cohort study among HIV-infected adult (≥18 years old) individuals attending care at Parirenyatwa hospital, Harare, Zimbabwe between October 2021 and April 2023. METHODS: Viral load and weight were assessed at both baseline and follow-up (≥24weeks) visits. HIVDR genotyping was performed by Sanger sequencing among participants with virological failure (viral load ≥1000 copies/ml) at follow-up visit. Factors associated with weight gain were determined using logistic regression analysis on STATA 17.0. RESULTS: One hundred and seventy-two participants were enrolled in the study. The median [interquartile range (IQR) age was 39 (29-48)] years whilst the median (IQR) CD4 + cell count and log 10 viral load at enrolment was 175 (58-328) cells/µl and 5.41 (4.80-5.74), respectively. After a median (IQR) duration of 27 (25-30) weeks on DTG, of the 131 participants with follow-up viral load data available, 129 (98%) had viral load less than 1000 copies/ml and among the 2 (2%) participants with viral load at least 1000 copies/ml, no emergent HIVDR was detected. We observed a significant increase in weight among the participants. The average weight gain was 5.25 kgs ( P  < 0.0001). Baseline CD4 + cell count at least 200 cells/µl was significantly associated with at a smaller weight gain [odds ratio (OR) = 0.26; 95% confidence interval (CI) 0.12-0.58, P  = 0.001]. CONCLUSION: We found high virological suppression and an increased weight among people initiating on DTG in a resource-limited setting. Encouragingly, HIVDR to DTG remains rare.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Oxazinas , Piperazinas , Piridonas , Adulto , Humanos , Adolescente , Infecções por HIV/tratamento farmacológico , Estudos Prospectivos , Zimbábue , Antirretrovirais/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , HIV , Carga Viral , Aumento de Peso , Fármacos Anti-HIV/uso terapêutico
4.
Pediatric Health Med Ther ; 14: 483-496, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38145055

RESUMO

Background: Gut microbiota play a key role in host health, with certain Bifidobacterium strains critical for immune development. The healthy gut of breastfed infants is dominated by these pioneer microbes, especially the strains that feed on human milk oligosaccharides. Objective: This is a scoping review of gut microbiome research from Zimbabwe. It focuses on distribution and dynamic changes of bifidobacteria, and milk components that promote growth of microbes in infants, together with the distribution of associated gut microbes in adults. Design: Online databases were searched for publications from 2000 to 2023. Results and Analysis: Fourteen publications on microbiota of infants and adults were included in this scoping review. Most were cross-sectional, while three were clinical trials/cohort protocols. Publications focused on pediatrics (78.5%), pregnant women (14.3%), and men (7.2%). Zimbabwe has a high burden of HIV; hence 35.7% of study populations were delineated by HIV status. The laboratory methods used included shotgun metagenomics (62%) or 16S rRNA gene amplicon sequencing. Almost 85% of the studies focused on total microbiome profiles and rarely reported the distribution of different Bifidobacterium species and variants. None of the papers studied human breast milk composition. There were reports of reduced abundance of beneficial genera in pregnant women, children, and adolescents living with HIV. Additionally, gut microbiota was reported to be poorly predictive of child growth and vaccine response, though this was not conclusive. Conclusion: There are few studies that characterize the gut microbiome by Zimbabwe-based researchers. However, studies on strain level diversity of Bifidobacterium and other key microbes, and their role in health during and beyond infancy, lag behind in Zimbabwe and other low- and middle-income countries. Such cohorts are needed to inform future mechanistic studies and downstream translational work such as next-generation probiotics and prebiotics.

5.
Viruses ; 15(9)2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37766288

RESUMO

Dolutegravir (DTG) use in combination with tenofovir and lamivudine (TLD) is scaling up in Africa. However, HIV drug resistance (HIVDR) data to DTG remain scarce in Zimbabwe. We assessed the prevalence and genetic mechanisms of DTG resistance in people living with HIV initiating on TLD. A prospective cohort study was conducted between October 2021 and April 2023 among antiretroviral therapy (ART) naïve adults (≥18 years) attending care at an HIV clinic in Zimbabwe. Pre-treatment drug resistance (PDR) was assessed prior to TLD initiation and viral load (VL) outcome and acquired drug resistance (ADR) to TLD were described after 24 weeks follow-up. In total, 172 participants were enrolled in the study. The median (IQR) age and log10 VL were 39 (29-48) years and 5.41 (4.80-5.74) copies/mL, respectively. At baseline, no PDR to DTG was found. However, as previously reported, PDR to non-nucleotide reverse transcriptase inhibitor (NNRTI) was high (15%) whilst PDR to NRTI was low (4%). After a median duration of 27 (25-30) weeks on TLD, virological suppression (VL < 1000 copies/mL) was 98% and among the 2 participants with VL ≥ 1000 copies/mL, no ADR was found. HIVDR to DTG is rare among ART naïve individuals. DTG is more likely to address the problems of HIVDR in Africa.


Assuntos
Lamivudina , Adulto , Humanos , Lamivudina/farmacologia , Lamivudina/uso terapêutico , Tenofovir/uso terapêutico , Zimbábue/epidemiologia , Prevalência , Estudos Prospectivos
7.
PLoS One ; 18(2): e0281279, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36787296

RESUMO

BACKGROUND: In Zimbabwe, children, adolescents and young adults living with HIV (CALWH) who are on public health antiretroviral therapy (ART) have inadequate viral load (VL) suppression. We assessed whether a clinic-based VL monitoring could decrease 12-month virologic failure rates among these CALWH. METHODS: The study was registered on ClinicalTrials.gov: NCT03986099. CALWH in care at Chidamoyo Christian Hospital (CCH) and 8 rural outreach sites (ROS) on long-term community-based ART were randomized (1:1) to 6 monthly VL monitoring by COBAS®Ampliprep®/Taqman48® HIV-1 at the provincial referral laboratory (PRL) as per standard of care (SOC) or by the clinic-based SAMBA II assay, Diagnostics for the Real World, at CCH. VL suppression, turn-around-time (TAT) for VL results, drug switching and drug resistance in second-line failure were assessed at 12 months. RESULTS: Of 390 CALWH enrolled 347 (89%) completed 12 months follow-up. Median (IQR) age and ART duration were 14.1 (9.7-18.2) and 6.4 (3.7-7.9) years, respectively. Over half (57%) of the participants were female. At enrolment, 78 (20%) had VL ≥1,000 copies/ml and VL suppression of 80% was unchanged after 12 months, with no significant difference between the SOC (81%) and the clinic-based (80%) arms (p = 0.528). Median (IQR) months to confirmatory VL result at CCH vs PRL was 4.0 (2.1-4.4) vs 4.5 (3.5-6.3) respectively; p = 0.027 at 12 months. Drug switching was documented among 26/347 (7%) participants with no difference between the median (IQR) time to switch in SOC vs clinic-based arms (5.1 (3.9-10.0) months vs 4.4 (2.5-8.4) respectively; p = 0.569). Out of 24 confirmed second-line failures, only 4/19 (21%) had protease inhibitor resistance. CONCLUSION: In rural Zimbabwe, the clinic-based SAMBA II assay was able to provide confirmatory VL results faster than the SOC VL assay at the PRL. However, this rapid TAT did not allow for a more efficient drug switch among these CALWH.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Soropositividade para HIV , HIV-1 , Humanos , Criança , Feminino , Adolescente , Adulto Jovem , Masculino , Fármacos Anti-HIV/uso terapêutico , Zimbábue/epidemiologia , Carga Viral/métodos , Soropositividade para HIV/tratamento farmacológico , Infecções por HIV/tratamento farmacológico
8.
AIDS Res Hum Retroviruses ; 38(10): 774-778, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35959737

RESUMO

Tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD) as a safe and more effective single daily dose regimen is rolling out in Africa for people living with HIV. Although access to viral load (VL) testing is improving, patients may still be transitioned to TLD with virological failure and potential drug resistance. We reviewed annual VL test results of 390 children and adolescents who had enrolled in a community-based antiretroviral therapy program in rural Zimbabwe between 2018 and 2019. VL testing was done by the near point of care simplified amplification-based assays (Diagnostics for the Real World, Sunnyvale, CA, USA) at Chidamoyo Christian Hospital and rate of virological suppression (VS) on TLD (VL <1,000 copies/mL) was assessed. Overall, 184 children and adolescents on TLD were enrolled in this study. The median [interquartile range (IQR)] age was 15 (11-19) years, above half of the participants were female (57%). Before switching to TLD, rate of VS was 76% (139/184). After a median (IQR) duration of 6.9 (5.5-9.1) months on TLD, VS was observed in 95% (174/184) of the participants. Of the 10 participants with VL ≥1,000 copies/mL on TLD, 90% (9/10) were failing on their previous regimens, 6 of 9 (67%) having been on boosted protease inhibitor-based regimens. A high rate (95%) of VS was observed among children and adolescents on TLD in rural Zimbabwe. TLD may address the problems of virological failure and emergence of resistance in Africa. However, longer follow-up might be needed to ascertain sustained VS in this vulnerable population. Randomized Control Trial NCT03986099.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Adulto Jovem , Fármacos Anti-HIV/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Infecções por HIV/tratamento farmacológico , Lamivudina/efeitos adversos , Oxazinas/efeitos adversos , Inibidores de Proteases/efeitos adversos , Tenofovir/efeitos adversos , Carga Viral , Zimbábue
11.
Int J Infect Dis ; 117: 356-360, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35134559

RESUMO

Detection and epidemiologic characterization of infectious disease outbreaks are key for early identification and response to potential pandemic threats. The rapid global spread of severe SARS-CoV-2 in 2020 highlighted the critical role of diagnostics in understanding the epidemiology of the virus early in the pandemic. As a natural extension of Abbott's work in diagnostics, virus discovery, and virus surveillance, the Abbott Pandemic Defense Coalition (APDC) was launched in early 2021. The APDC is a global multisector scientific and public health partnership whose primary objective is the early detection and mitigation of infectious disease threats of pandemic potential. As of January 2022, the APDC network has partners on 5 continents including academic institutions, governmental, and nongovernmental organizations. A novel element of the APDC is the capacity for early development and rapid deployment of scalable, quality diagnostics targeting newly identified pathogens of pandemic potential.


Assuntos
COVID-19 , Pandemias , COVID-19/epidemiologia , COVID-19/prevenção & controle , Surtos de Doenças , Humanos , Pandemias/prevenção & controle , Saúde Pública , SARS-CoV-2
13.
Pan Afr Med J ; 40: 57, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34795836

RESUMO

INTRODUCTION: pre-treatment drug resistance (PDR) can compromise the 3rd 95-95-95 global target for viral load suppression. The high complexity and cost of genotyping assays limits routine testing in many resource limited settings (RLS). We assessed the performance of a rapid HIV-1 drug resistance assay, the Pan Degenerate Amplification and Adaptation (PANDAA) assay when screening for significant HIV-1 drug resistance mutations (DRMs) such as K65R, K103NS, M184VI, Y181C and G190A. Methods: we used previously generated amplicons from a cross-sectional study conducted between October 2018 and February 2020 of HIV-1 infected antiretroviral therapy (ART)-naïve or those reinitiating 1st line ART (18 years or older). The performance of the PANDAA assay in screening K65R, K103NS, M184VI, Y181C, and G190A mutations compared to the reference assay, Sanger sequencing was evaluated by Cohen´s kappa coefficient on Stata version 14 (StataCorp LP, College Station, TX, USA). RESULTS: one hundred and twenty samples previously characterized by Sanger sequencing were assessed using PANDAA. PDR was found in 14% (17/120). PDR to non-nucleoside reverse transcriptase inhibitors (NNRTIs) was higher at 13% (16/120) than PDR to nucleotide reverse transcriptase inhibitors (NRTIs), 3% (3/120). The PANDAA assay showed a strong agreement with the reference assay, i.e. Sanger sequencing for all five target DRMs (kappa (95%CI); 0.93 (0.78-0.98)) and NNRTI DRMs (kappa (95%CI); 0.93 (0.77-0.980), and a perfect agreement for NRTI DRMs (kappa (95%CI); 1.00 (0.54-1.00)). CONCLUSION: the PANDAA assay is a simple and rapid method to identify significant HIV DRMs in plasma samples as an alternative to Sanger sequencing in many RLS.


Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Adulto , Estudos Transversais , Feminino , Genótipo , Infecções por HIV/virologia , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação
14.
PLoS One ; 16(11): e0260261, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34813627

RESUMO

BACKGROUND: Healthcare workers are disproportionately affected by COVID-19. In low- and middle- income countries, they may be particularly impacted by underfunded health systems, lack of personal protective equipment, challenging working conditions and barriers in accessing personal healthcare. METHODS: In this cross-sectional study, occupational health screening was implemented at the largest public sector medical centre in Harare, Zimbabwe, during the "first wave" of the country's COVID-19 epidemic. Clients were voluntarily screened for symptoms of COVID-19, and if present, offered a SARS-CoV-2 nucleic acid detection assay. In addition, measurement of height, weight, blood pressure and HbA1c, HIV and TB testing, and mental health screening using the Shona Symptom Questionnaire (SSQ-14) were offered. An interviewer-administered questionnaire ascertained client knowledge and experiences related to COVID-19. RESULTS: Between 27th July and 30th October 2020, 951 healthcare workers accessed the service; 210 (22%) were tested for SARS-CoV-2, of whom 12 (5.7%) tested positive. Clients reported high levels of concern about COVID-19 which declined with time, and faced barriers including lack of resources for infection prevention and control. There was a high prevalence of largely undiagnosed non-communicable disease: 61% were overweight or obese, 34% had a blood pressure of 140/90mmHg or above, 10% had an HbA1c diagnostic of diabetes, and 7% had an SSQ-14 score consistent with a common mental disorder. Overall 8% were HIV-positive, with 97% previously diagnosed and on treatment. CONCLUSIONS: Cases of SARS-CoV-2 in healthcare workers mirrored the national epidemic curve. Implementation of comprehensive occupational health services during a pandemic was feasible, and uptake was high. Other comorbidities were highly prevalent, which may be risk factors for severe COVID-19 but are also important independent causes of morbidity and mortality. Healthcare workers are critical to combatting COVID-19; it is essential to support their physical and psychological wellbeing during the pandemic and beyond.


Assuntos
COVID-19/prevenção & controle , Atenção à Saúde/normas , Pessoal de Saúde/estatística & dados numéricos , Serviços de Saúde do Trabalhador/normas , Saúde Ocupacional/normas , Equipamento de Proteção Individual/normas , Adulto , COVID-19/epidemiologia , COVID-19/transmissão , COVID-19/virologia , Estudos Transversais , Feminino , Humanos , Masculino , SARS-CoV-2 , Zimbábue/epidemiologia
15.
Pan Afr Med J ; 39: 255, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34707756

RESUMO

In response to COVID-19 pandemic, the Zimbabwe government put in place various rigorous measures to curb the spread of the virus. Although roll-out and access to COVID-19 vaccines in Africa have been slow, the World Health Organization (WHO)-led COVID-19 Vaccines Global Access (COVAX) consortium and the African vaccine acquisition task team are striving to provide 720 million doses of COVID-19 vaccines to achieve 60% coverage in Africa by June, 2022. In line with this, the Zimbabwe vaccination programme commenced on the 26th February 2021 and as of 9th June 2021, approximately, 2.6% of the population have been fully vaccinated in the country. Although the COVID-19 pandemic has crippled the economy and caused significant strain on the public health system, much has been done in the country since the first case was recorded (20th March 2020). However, much more needs to be done to finally reach the expected 60% herd immunity by June 2022.


Assuntos
Vacinas contra COVID-19 , COVID-19/prevenção & controle , Imunidade Coletiva , Pandemias/prevenção & controle , COVID-19/epidemiologia , Humanos , SARS-CoV-2 , Zimbábue
16.
AIDS Res Hum Retroviruses ; 37(12): 954-961, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34714124

RESUMO

Previously used as part of salvage therapy, integrase strand transfer inhibitors (INSTIs) have become part of the preferred antiretroviral therapy (ART) first-line regimen in most low- to middle-income countries. With the extensive use of dolutegravir in first-line ART, drug resistance mutations to INSTIs are inevitable. Therefore, active monitoring and surveillance of INSTI drug resistance is required. The aim of this study was to evaluate the genetic diversity of the integrase gene and determine pretreatment INSTI resistance in Harare, Zimbabwe. Forty-four HIV-1 Integrase sequences from 65 were obtained from treatment-naive individuals using a custom genotyping method. Drug resistance mutations were determined using the Stanford HIV Drug Resistance Interpretation program. Viral subtyping was done by phylogenetic analysis and the REGA HIV subtyping tool determined recombinants. Natural polymorphisms were evaluated relative to the global subtype B and C consensus sequences. One hundred ninety-two sequences from the region were accessed from GenBank to assess differences between the Zimbabwean sequences and those from neighboring countries. No major INSTI resistance mutations were detected; however, the L74I polymorphism was detected in three sequences of the 44 (6.8%). There was little genetic variability in the Integrase gene, with a mean genetic distance range of 0.053015. The subtype C consensus was identical to the global subtype C consensus and varied from the global subtype B consensus at five major positions: T124A, V201I, T218I, D278A, and S283G. This study has provided baseline sequence data on the presence of HIV-1 subtype C Integrase gene drug resistance mutations from Harare, Zimbabwe.


Assuntos
Infecções por HIV , Inibidores de Integrase de HIV , Integrase de HIV , HIV-1 , Farmacorresistência Viral/genética , Genótipo , Infecções por HIV/tratamento farmacológico , Integrase de HIV/genética , Inibidores de Integrase de HIV/farmacologia , Inibidores de Integrase de HIV/uso terapêutico , HIV-1/genética , Humanos , Mutação , Filogenia , Polimorfismo Genético , Zimbábue
17.
Viruses ; 13(6)2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208165

RESUMO

Affordable, sensitive, and scalable technologies are needed for monitoring antiretroviral treatment (ART) success with the goal of eradicating HIV-1 infection. This review discusses use of Sanger sequencing and next generation sequencing (NGS) methods for HIV-1 drug resistance (HIVDR) genotyping, focusing on their use in resource limited settings (RLS). Sanger sequencing remains the gold-standard method for detecting HIVDR mutations of clinical relevance but is mainly limited by high sequencing costs and low-throughput. NGS is becoming a more common sequencing method, with the ability to detect low-abundance drug-resistant variants and reduce per sample costs through sample pooling and massive parallel sequencing. However, use of NGS in RLS is mainly limited by infrastructure costs. Given these shortcomings, our review discusses sequencing technologies for HIVDR genotyping, focusing on common in-house and commercial assays, challenges with Sanger sequencing in keeping up with changes in HIV-1 treatment programs, as well as challenges with NGS that limit its implementation in RLS and in clinical diagnostics. We further discuss knowledge gaps and offer recommendations on how to overcome existing barriers for implementing HIVDR genotyping in RLS, to make informed clinical decisions that improve quality of life for people living with HIV.


Assuntos
Farmacorresistência Viral , Genótipo , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Técnicas de Genotipagem , Infecções por HIV/tratamento farmacológico , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação
18.
AIDS Res Hum Retroviruses ; 37(10): 776-783, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33430681

RESUMO

Pretreatment drug resistance (PDR) can compromise antiretroviral therapy (ART) efficacy and undermine the WHO targets to end the AIDS epidemic as a public health threat by 2030. Thus, we examined the level of PDR in Harare, Zimbabwe. Eligible study participants were adults who were ART naive or individuals with previous ART exposure reinitiating treatment, recruited between October 2018 and February 2020 in a HIV ART treatment clinic, in Harare. HIV drug resistance tests were performed for all specimens with viral load ≥400 copies/mL and interpreted using the Stanford HIVDB Algorithm. Chi-square test or Fisher's exact test was used for comparison of proportions of PDR across ART-naive or prior ART-exposed participants. All statistical analyses were performed using Stata version 14. Overall, 120 samples were genotyped of whom 104 were ART naive and 16 reported previous ART exposure. The overall PDR frequency among all participants was 31% [95% confidence interval (CI): 22.5-39.6]. PDR to any non-nucleotide reverse transcriptase inhibitor (NNRTI) was reported in 29% (95% CI: 21.0-37.9). PDR to nucleotide reverse transcriptase inhibitors (NRTIs) and protease inhibitors were low, found in 3% (95% CI: 0.9-8.2) and 1% (95% CI: 0.02-4.52), respectively. PDR to NNRTIs [efavirenz/nevirapine (EFV/NVP)] was found in 17% (95% CI: 10.5-24.6) and was more than six times higher among people with previous ART exposure than ART-naive people: 63% versus 10%, p < .001. Our study shows that PDR to NNRTIs in Zimbabwe has remarkably increased from the 10.9% prevalence reported in the 2016 WHO survey. Addressing PDR at a national level is a critical need and will be facilitated by fast-tracking the transition to dolutegravir in first-line ART regimens.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Adulto , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , HIV-1/genética , Compostos Heterocíclicos com 3 Anéis , Humanos , Oxazinas , Piperazinas , Piridonas , Carga Viral , Zimbábue/epidemiologia
19.
PLoS One ; 16(1): e0245085, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33444325

RESUMO

INTRODUCTION: Maintaining virologic suppression of children and adolescents on ART in rural communities in sub-Saharan Africa is challenging. We explored switching drug regimens to protease inhibitor (PI) based treatment and reducing nevirapine and zidovudine use in a differentiated community service delivery model in rural Zimbabwe. METHODS: From 2016 through 2018, we followed 306 children and adolescents on ART in Hurungwe, Zimbabwe at Chidamoyo Christian Hospital, which provides compact ART regimens at 8 dispersed rural community outreach sites. Viral load testing was performed (2016) by Roche and at follow-up (2018) by a point of care viral load assay. Virologic failure was defined as viral load ≥1,000 copies/ml. A logistic regression model which included demographics, treatment regimens and caregiver's characteristics was used to assess risks for virologic failure and loss to follow-up (LTFU). RESULTS: At baseline in 2016, 296 of 306 children and adolescents (97%) were on first-line ART, and only 10 were receiving a PI-based regimen. The median age was 12 years (IQR 8-15) and 55% were female. Two hundred and nine (68%) had viral load suppression (<1,000 copies/ml) and 97(32%) were unsuppressed (viral load ≥1000). At follow-up in 2018, 42/306 (14%) were either transferred 23 (7%) or LTFU 17 (6%) and 2 had died. In 2018, of the 264 retained in care, 107/264 (41%), had been switched to second-line, ritonavir-boosted PI with abacavir as a new nucleotide analog reverse transcriptase inhibitor (NRTI). Overall viral load suppression increased from 68% in 2016 to 81% in 2018 (P<0.001). CONCLUSION: Viral load testing, and switching to second-line, ritonavir-boosted PI with abacavir significantly increased virologic suppression among HIV-infected children and adolescents in rural Zimbabwe.


Assuntos
Antirretrovirais/administração & dosagem , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , HIV-1/metabolismo , População Rural , Carga Viral , Adolescente , Criança , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Zimbábue
20.
Pan Afr Med J ; 40: 183, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35059103

RESUMO

INTRODUCTION: coronavirus disease 2019 (COVID-19) has become a major public health problem and has spread rapidly around the globe since its first identification in Wuhan, China, in December 2019. Zimbabwe reported its first case on the 20th March 2020, and since then the disease has spread to almost every part of the country. Laboratory testing is important in controlling this pandemic. However, few studies have focused on assessing trends of SARS-CoV-2 laboratory data. We described SARS-CoV-2 data from African Institute of Biomedical Science and Technology (AiBST) Laboratory in Harare, Zimbabwe. METHODS: a retrospective record review of secondary SARS-CoV-2 data from AiBST Laboratory in Harare between May to September 2020 was done. Epi Info TM 7.2.2.6 was used to generate frequencies, proportions and conduct bivariate analysis. RESULTS: a total of 6,535 SARS-CoV-2 laboratory records were analysed. The median age of the patients was 36 years and 55% (3594/6535) were males. There was an increase in average analytical turn-around time (TAT) of SARS-CoV-2 results from May to August 2020. Analytical and preanalytical TAT remained above 2 days from August to September. Males were 1.18 times at risk of being SARS-CoV-2 infected than females (p<0.05). The risk of being SARS-CoV-2 infected increased with age from 1.06 in the 11-20 age group to 1.45 in the 41-50 age group. CONCLUSION: COVID-19 poses a greater threat to the older age groups and to men. The delayed TAT of SARS-CoV-2 results limits the efforts to control the pandemic. Decentralization of testing to provincial and district level would help improve result TAT.


Assuntos
COVID-19 , Adulto , Idoso , Feminino , Humanos , Laboratórios , Masculino , Estudos Retrospectivos , SARS-CoV-2 , Zimbábue/epidemiologia
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