14 research outputs found

    Rapid HIV-1 drug resistance testing in a resource limited setting: the Pan Degenerate Amplification and Adaptation assay (PANDAA)

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    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)-naĂŻve 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

    Effects of repeated blood donation on iron status of blood donors in Zimbabwe: A cross-sectional study.

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    INTRODUCTION: Iron deficiency is a major complication of repeated blood donation. However, most of the blood screening methods employed by blood collection agents do not include iron status markers, leading to possible subclinical iron deficiency. The aim of this study was to evaluate the effects of repeated blood donation on the iron status of this vulnerable population in Zimbabwe. METHODS: All donors were categorized into groups based on number of donations made in the previous 2-year period prior to enrolment into the study. Serum iron, total iron-binding capacity (TIBC), and ferritin were analyzed on automated chemistry analyzers while transferrin saturation (TSAT) was calculated. The Wilcoxon rank-sum and ANOVA tests were used to assess the variation of iron profiles by gender and frequency of donations. All data analysis was performed using Stata software v13. RESULTS: Study participants included 170 repeat donors and 20 first-time blood donors. The median (IQR) age was 23 (19-27) years, while the majority were males 57% (n = 109/190). The overall prevalence of iron deficiency and reduced iron stores was 12.6% and 38.9%, respectively. There were statistically significant differences between males and females in all the iron status parameters (P < .05). TIBC increased with number of donations, while iron, ferritin, and TSAT decreased with increased number of donations. CONCLUSION: A high proportion of blood donors had iron deficiency despite being eligible to donate. Repeated blood donation may lead to substantial reduction in iron stores among blood donors. Inclusion of iron biochemical markers may enhance proper screening and monitoring of blood donors in Zimbabwe to prevent development of iron deficiency anemia

    Tenofovir, Lamivudine and Dolutegravir (TLD) among Rural Adolescents in Zimbabwe, a Cautionary Tale.

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    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 programme 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 California) at Chidamoyo Christian Hospital. Rate of virological suppression (VS) on TLD (VL<1000 copies/ml) was assessed. Overall, 184 children and adolescents on TLD were enrolled in this study. The median (IQR) age was 15 (11-19) years, above half of the participants were female (57%). Prior to 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 ≥1000 copies/ml on TLD, 90% (9/10) were failing on their previous regimens, 6/9 (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 virologic failure and emergence of resistance in Africa. However, longer follow up might be needed to ascertain sustained VS in this vulnerable population

    Clinic-based SAMBA-II vs centralized laboratory viral load assays among HIV-1 infected children, adolescents and young adults in rural Zimbabwe: A randomized controlled trial.

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    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

    African women in science and development, bridging the gender gap

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    Science and technology play a fundamental role in driving social progress and economic growth in today's rapidly evolving world. Yet, despite considerable advancements, the gender gap in science remains a harsh reality, particularly for African women. This inequality directly impedes their invaluable perspectives and contributions to scientific advancements and innovations. Africa's development requires significant investment in science, technology, engineering, and mathematics (STEM) fields and leadership. This opinion piece delves into the gender disparity prevailing in STEM, emphasizes the challenges that African women experience, highlights the immense potential that African women possess, and finally advocates for immediate efforts to bridge this gap

    Low Prevalence of Pre-Treatment and Acquired Drug Resistance to Dolutegravir among Treatment NaĂŻve Individuals Initiating on Tenofovir, Lamivudine and Dolutegravir in Zimbabwe

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    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

    The transient effect of a peer support intervention to improve adherence among adolescents and young adults failing antiretroviral therapy in Harare, Zimbabwe: a randomized control trial

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    Abstract Background Adolescents and young adults living with HIV in sub Saharan Africa are at high risk of poor adherence to antiretroviral therapy (ART) and virologic failure (VF). Methods We conducted a randomized control trial among adolescents and young adults on ART with VF to assess the effectiveness of a community-based peer support intervention aimed at improving VF. Viral load (VL) levels were obtained at 12, 24 and 36 weeks. A subset of the participants had baseline HIV drug resistance (HIVDR) genotyped using Sanger sequencing. Results The participants’ median (interquartile range (IQR)) age was 18.1 (IQR: 15.1–20.0) years and half (50.5%, n = 107) were male. At week 24, the proportion of subjects with a detectable viremia was significantly lower in the intervention arm than in the standard of care (SOC) arm (76.0% (n = 79) vs. 89.0% (n = 96), p = 0.013). At Week 36, there remained a difference in the proportion of subjects with a detectable VL between the intervention arm (68.3%, n = 71) and SOC arm (79.6%, n = 86), which was trending towards statistical significance (p = 0.059). There was no difference in the probability of having a detectable VL over time between the intervention and SOC groups (adjusted odds ratio: 1.14, p = 0.439). Baseline HIVDR was observed in 44.0% of the participants in the intervention and 56.0% in the SOC group (p = 0.146). Conclusion A transient effect of the peer support intervention in improving VF was observed among adolescents and young people failing ART. Trial registration: This study is registered with www.clinicaltrials.gov under the reference number: NCT0283344

    Drug Resistance Among Adolescents and Young Adults with Virologic Failure of First-Line Antiretroviral Therapy and Response to Second-Line Treatment.

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    Barriers to sustainable virologic suppression (VS) of HIV-infected adolescents and young adults include drug resistance mutations (DRMs) and limited treatment options, which may impact the outcome of second-line antiretroviral therapy (ART). We sequenced plasma viral RNA from 74 adolescents and young adults (16-24 years) failing first-line ART at Newlands Clinic, Zimbabwe between October 2015 and December 2016. We evaluated first-line nucleoside reverse transcriptase inhibitor (NRTI) susceptibility scores to first- and second-line regimens. Boosted protease inhibitor (bPI)-based ART was provided and viral load (VL) monitored for ≥48 weeks. Fisher's exact test was used to evaluate factors associated with VS on second-line regimens, defined as VL <1,000 copies/mL (VS1,000) or <50 copies/mL (VS50). The 74 participants on first-line ART had a median [interquartile range (IQR)] age of 18 (16-21) years and 42 (57%) were female. The mean (±standard deviation) duration on ART was 5.5 (±3.06) years and the median (IQR) log10 VL was 4.26 (3.78-4.83) copies/mL. After switching to a second-line PI regimen, 88% suppressed to <1,000 copies/mL and 76% to <50 copies/mL at ≥48 weeks. A new NRTI was associated with increased VS50 (p = .031). These 74 adolescents and young adults failing first-line ART demonstrated high levels (97%) of DRMs, despite enhanced adherence counseling. Switching to new NRTIs in second-line improved VS. With the widespread adoption of generic dolutegravir, lamivudine and tenofovir combinations in Africa, genotyping to determine NRTI susceptibility, may be warranted

    HIV-1 Genetic Diversity and Natural Polymorphisms of the Integrase Gene in Integrase Inhibitor-Naive Patients in Harare, Zimbabwe.

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    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
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