Strengthening HIV therapy and care in rural Tanzania affects rates of viral suppression

Ntamatungiro, Alex J; Muri, Lukas; Glass, Tracy R.; Erb, Stefan; Battegay, Manuel; Furrer, Hansjakob; Hatz, Christoph; Tanner, Marcel; Felger, Ingrid; Klimkait, Thomas; Letang, Emílio

doi:10.1093/jac/dkx095

Cited by 16 publications

(13 citation statements)

References 29 publications

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“…The prevalence of HIV-DRM of 90.4% in children and adolescents with virologic failure in our cohort is comparable with similar settings [9,29–30] and the adult population in our clinic [31]. The multiclass resistances, present in almost 80% of all failing patients dramatically limits future treatment options and represents an important public health concern.…”

Section: Discussionsupporting

confidence: 72%

Development of HIV drug resistance and therapeutic failure in children and adolescents in rural Tanzania

Muri

Gamell

Ntamatungiro

et al. 2017

Aids

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104

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Objective:To investigate the prevalence and determinants of virologic failure and acquired drug resistance-associated mutations (DRMs) in HIV-infected children and adolescents in rural Tanzania.Design:Prospective cohort study with cross-sectional analysis.Methods:All children 18 years or less attending the paediatric HIV Clinic of Ifakara and on antiretroviral therapy (ART) for at least 12 months were enrolled. Participants with virologic failure were tested for HIV-DRM. Pre-ART samples were used to discriminate acquired and transmitted resistances. Multivariate logistic regression analysis identified factors associated with virologic failure and the acquisition of HIV-DRM.Results:Among 213 children on ART for a median of 4.3 years, 25.4% failed virologically. ART-associated DRM were identified in 90%, with multiclass resistances in 79%. Pre-ART data suggested that more than 85% had acquired key mutations during treatment. Suboptimal adherence [odds ratio (OR) = 3.90; 95% confidence interval (CI) 1.11–13.68], female sex (aOR = 2.57; 95% CI 1.03–6.45), and current nonnucleoside reverse transcriptase inhibitor-based ART (aOR = 7.32; 95% CI 1.51–35.46 compared with protease inhibitor-based) independently increased the odds of virologic failure. CD4+ T-cell percentage (aOR = 0.20; 0.10–0.40 per additional 10%) and older age at ART initiation (aOR = 0.84 per additional year of age; 95% CI 0.73–0.97) were protective (also in predicting acquired HIV-DRM). At the time of virologic failure, less than 5% of the children fulfilled the WHO criteria for immunologic failure.Conclusion:Virologic failure rates in children and adolescents were high, with the majority of ART-failing children harbouring HIV-DRM. The WHO criteria for immunologic treatment failure yielded an unacceptably low sensitivity. Viral load monitoring is urgently needed to maintain future treatment options for the millions of African children living with HIV.

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Section: Discussionsupporting

confidence: 72%

Development of HIV drug resistance and therapeutic failure in children and adolescents in rural Tanzania

Muri

Gamell

Ntamatungiro

et al. 2017

Aids

Self Cite

104

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“…bPI-associated DRM n (%) resistance remained stable over time [5]. Similar studies on virologic failure rates on bPI-based treatment from other SSA settings report failure rates ranging from 11.1% [16] to 26% [17].…”

Section: Discussionsupporting

confidence: 54%

“…In all patients with virologic failure, 75.7% showed drug resistance mutations (DRM) to the backbone nucleoside analogues (NRTI) and to non-nucleoside reverse transcriptase inhibitors (NNRTI) [4]. In a previous study from our cohort in rural southern Tanzania, the overall VF rate was 9% in patients failing on first-line ART with 81% demonstrating DRM to NRTIs or NNRTIs [5].…”

Section: Introductionmentioning

confidence: 77%

High failure rates of protease inhibitor-based antiretroviral treatment in rural Tanzania – A prospective cohort study

et al. 2020

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Background Poor adherence to antiretroviral drugs and viral resistance are the main drivers of treatment failure in HIV-infected patients. In sub-Saharan Africa, avoidance of treatment failure on second-line protease inhibitor therapy is critical as treatment options are limited. Methods In the prospective observational study of the Kilombero & Ulanga Antiretroviral Cohort in rural Tanzania, we assessed virologic failure (viral load �1,000 copies/mL) and drug resistance mutations in bio-banked plasma samples 6-12 months after initiation of a protease inhibitor-based treatment regimen. Additionally, viral load was measured before start of protease inhibitor, a second time between 1-5 years after start, and at suspected treatment failure in patients with available bio-banked samples. We performed resistance testing if viral load was �1000 copies/ml. Risk factors for virologic failure were analyzed using logistic regression. Results In total, 252 patients were included; of those 56% were female and 21% children. Virologic failure occurred 6-12 months after the start of a protease inhibitor in 26/199 (13.1%) of adults and 7/53 of children (13.2%). The prevalence of virologic failure did not change over time. Nucleoside reverse transcriptase inhibitors drug resistance mutation testing performed at 6-12 months showed a positive signal in only 9/16 adults. No cases of resistance mutations for protease inhibitors were seen at this time. In samples taken between 1-5 years protease inhibitor resistance was demonstrated in 2/7 adults. In adult samples before protease

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“…The high viral suppression seen in Shinyanga signifies considerably successful treatment outcomes among those on ART and aligns with the evidence showing high viral load suppression in rural East Africa when treatment is well managed [56,57]. Ultimately, managing the HIV response in Shinyanga should focus on closing the testing and treatment access gaps.…”

Section: Discussionsupporting

confidence: 53%

The Shinyanga Patient: A Patient’s Journey through HIV Treatment Cascade in Rural Tanzania

Okere

Sambu²,

Ndungile³

et al. 2021

IJERPH

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The 2016–2017 Tanzania HIV Impact Survey (THIS) reported the accomplishments towards the 90-90-90 global HIV targets at 61-94-87, affirming the need to focus on the first 90 (i.e., getting 90% of people living with HIV (PLHIV) tested). We conducted a patient-pathway analysis to understand the gap observed, by assessing the alignment between where PLHIV seek healthcare and where HIV services are available in the Shinyanga region, Tanzania. We used existing and publicly available data from the National AIDS Control program, national surveys, registries, and relevant national reports. Region-wide, the majority (n = 458/722, 64%) of THIS respondents accessed their last HIV test at public sector facilities. There were 65.9%, 45.1%, and 74.1% who could also access antiretroviral therapy (ART), CD4 testing, and HIV viral load testing at the location of their last HIV test, respectively. In 2019, the viral suppression rate estimated among PLHIV on ART in the Shinyanga region was 91.5%. PLHIV access HIV testing mostly in public health facilities; our research shows that synergies can be achieved to improve access to services further down the cascade in this sector. Furthermore, effective engagement with the private sector (not-for-profit and for-profit) will help to achieve the last mile toward ending the HIV epidemic.

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Strengthening HIV therapy and care in rural Tanzania affects rates of viral suppression

Abstract: †Equal contribution. ‡Other members of the KIULARCO Study Group are listed in the Acknowledgements section.

Cited by 16 publications

References 29 publications

Development of HIV drug resistance and therapeutic failure in children and adolescents in rural Tanzania

Development of HIV drug resistance and therapeutic failure in children and adolescents in rural Tanzania

High failure rates of protease inhibitor-based antiretroviral treatment in rural Tanzania – A prospective cohort study

The Shinyanga Patient: A Patient’s Journey through HIV Treatment Cascade in Rural Tanzania

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