Virological Response and Antiretroviral Drug Resistance Emerging during Antiretroviral Therapy at Three Treatment Centers in Uganda

Kaleebu, Pontiano; Kirungi, Wilford; Watera, Christine; Asio, Juliet; Lyagoba, Fred; Lutalo, Tom; Kapaata, Anne; Nanyonga, Faith Elizabeth; Parry, Chris M.; Magambo, Brian; Nazziwa, Jamirah; Nannyonjo, Maria; Hughes, Peter J.; Hladik, Wolfgang; Ruberantwari, Anthony; Namuwenge, Norah; Musinguzi, Joshua; Downing, Robert; Katongole‐Mbidde, Edward

doi:10.1371/journal.pone.0145536

Cited by 26 publications

(47 citation statements)

References 17 publications

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“…On the contrary, in a study in Myanmar, 94% of patients had an undetectable viral load and only 4% had ART failure. It is further reported that 84.7% of respondents on first and second line treatment in the Myanmar study had viral load below 1000 copies/ml [24]. The viral loads in this study support the pill count adherence method as the viral loads depict the adherence level in patients.…”

Section: Respondent's Last Viral Loadsupporting

confidence: 70%

Factors Associated with Non-Adherence to Antiretroviral Treatment in Adults at Keetmanshoop District State Hospital in Namibia

Dolamo¹

2017

ACRS

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BackgroundNamibia's Anti-Retroviral Therapy (ART) roll out has been very successful, achieving more than 84% coverage against a national target of 90% [1]. However, despite the successful role out of ART in Namibia, patients often fail to meet the level of adherence required for successful ART. The challenge of non-adherence to ART treatment has also been noted at the study site. In a study done in Nigeria, outcomes of non-adherence to ARV medication included viral resistance, treatment failure, toxicities and waste of financial resources [2]. Results from a study conducted in Botswana concluded that there is a strong correlation between adherence and clinical outcomes [3]. Given the large number of patients whose HIV infection will progress to AIDS if adherence is suboptimal, research is urgently needed to determine factors influencing adherence so that the most effective interventions to ensure adherence in African cohorts can be employed [4]. In a study in Ethiopia, 26.5% of the respondents had sub optimal adherence [5]. Locally, a recent study from Northern Namibia reported that 22% of respondents were non-adherent measured by pill count assessment. Henceforth this study envisaged to identify factors associated with non-adherence to ARV treatment in adult patients at Keetmanshoop hospital in Namibia.Focusing on the study site, in January 2015, the Keetmanshoop Hospital had 1289 adults receiving ART. On average, the clinic serves about 250 to 400 patients in a month. In the period October to December 2014 a total of 933 patients received follow-up care at the study site. Of these patients 53% (n=530) achieved required adherence scores of more than or equal to 95% while approximately 47% (n=403) achieved less than the required 95%. The suboptimal adherence rate in 47% of the patients 36.7% found in January 2015 at the Keetmanshoop Hospital was significantly higher than that reported in the Northern parts of the country. The Health Belief Model (HBM) was the theory of choice in this study due to its applicability to patient adherence and preventative health practices. The HBM has four major components [6,7]. HSOA Journal of AIDS Clinical Research and STDs Research ArticleAbstract Aim: To identify the factors associated with non-adherence to Antiretroviral Treatment (ART) amongst adult patients at a hospital in Namibia.Methods: Quantitative and qualitative approaches were employed, study sample of 112 adults aged 21 years and older at Keetmanshoop District State Hospital participated. Adherence to ART was assessed using the pill count and self-report methods. A questionnaire with a Cronbach value of 0.8 was used. Census and multi-stage sampling was applied. Data was collected from August to September 2016 through structured interviews and patients records review. Correlation of variables was done to remove multicollinearity. Stata version 12 was used for logistic regression to do univariate and multivariate analysis to determine factors associated with missing five or more doses. Results:In the univariate analy...

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Section: Respondent's Last Viral Loadsupporting

confidence: 70%

Factors Associated with Non-Adherence to Antiretroviral Treatment in Adults at Keetmanshoop District State Hospital in Namibia

Dolamo¹

2017

ACRS

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“…However, given that stavudine is no longer being prescribed in Uganda and in most resource‐limited settings in accordance with the WHO ART guidelines , this issue will probably be less of a problem in the future, which is somewhat reassuring. Fortunately, we also found a fairly low prevalence of the K65R mutation (in 11% of individuals with virological failure), which is another NRTI resistance mutation that can confer pan‐NRTI resistance, although one study reported that K65R mutations are likely to increase with increased use of tenofovir as a first‐line option . VL measurement with enhanced adherence counselling has been demonstrated to be effective for individuals who are in the first few years of ART in South Africa .…”

Section: Discussionmentioning

confidence: 70%

Lack of effectiveness of adherence counselling in reversing virological failure among patients on long‐term antiretroviral therapy in rural Uganda

et al. 2019

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ObjectivesThe current World Health Organization and Uganda Ministry of Health HIV treatment guidelines recommend that asymptomatic patients who have a viral load (VL) ≥ 1000 HIV‐1 RNA copies/mL should receive adherence counselling and repeat VL testing before switching to second‐line therapy. We evaluated the effectiveness of this strategy in a large HIV treatment programme of The AIDS Support Organisation Jinja in Jinja, Uganda.MethodsWe measured the HIV VL at enrolment, and for participants with VL ≥ 1000 copies/mL we informed them of their result, offered enhanced adherence counselling and repeated the VL measurement after 3 months. All blood samples with VL ≥ 1000 copies/mL were sequenced in the polymerase (pol) region, a 1257‐bp fragment spanning the protease and reverse transcriptase genes.ResultsOne thousand and ninety‐one participants were enrolled in the study; 74.7% were female and the median age was 44 years [interquartile range (IQR) 39–50 years]. The median time on antiretroviral therapy (ART) at enrolment was 6.75 years (IQR 5.3–7.6 years) and the median CD4 cell count was 494 cells/μL (IQR 351–691 cells/μL). A total of 113 participants (10.4%) had VLs ≥ 1000 copies/mL and were informed of the VL result and its implications and given adherence counselling. Of these 113 participants, 102 completed 3 months of follow‐up and 93 (91%) still had VLs ≥ 1000 copies/mL. We successfully genotyped HIV for 105 patients (93%) and found that 103 (98%) had at least one mutation: eight (7.6%) had only one mutation, 94 (89.5%) had two mutations and one sample (1%) had three mutations.ConclusionsIn this study, enhanced adherence counselling was not effective in reversing virologically defined treatment failure for patients on long‐term ART who had not previously had a VL test.

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“…22,23 The third possibility, which we believe could account for most of the TAMs in the present study is previous undisclosed ART use with undocumented viral failure and drug resistance. This hypothesis is supported by the lower CD4 counts detected in patients with TAMs.…”

Section: Discussionmentioning

confidence: 72%

Occult HIV-1 drug resistance to thymidine analogues following failure of first-line tenofovir combined with a cytosine analogue and nevirapine or efavirenz in sub Saharan Africa: a retrospective multi-centre cohort study

Gregson

Kaleebu

Marconi

et al. 2017

The Lancet Infectious Diseases

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SummaryBackgroundHIV-1 drug resistance to older thymidine analogue nucleoside reverse transcriptase inhibitor drugs has been identified in sub-Saharan Africa in patients with virological failure of first-line combination antiretroviral therapy (ART) containing the modern nucleoside reverse transcriptase inhibitor tenofovir. We aimed to investigate the prevalence and correlates of thymidine analogue mutations (TAM) in patients with virological failure of first-line tenofovir-containing ART.MethodsWe retrospectively analysed patients from 20 studies within the TenoRes collaboration who had locally defined viral failure on first-line therapy with tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleoside reverse transcriptase inhibitor (NNRTI; nevirapine or efavirenz) in sub-Saharan Africa. Baseline visits in these studies occurred between 2005 and 2013. To assess between-study and within-study associations, we used meta-regression and meta-analyses to compare patients with and without TAMs for the presence of resistance to tenofovir, cytosine analogue, or NNRTIs.FindingsOf 712 individuals with failure of first-line tenofovir-containing regimens, 115 (16%) had at least one TAM. In crude comparisons, patients with TAMs had lower CD4 counts at treatment initiation than did patients without TAMs (60·5 cells per μL [IQR 21·0–128·0] in patients with TAMS vs 95·0 cells per μL [37·0–177·0] in patients without TAMs; p=0·007) and were more likely to have tenofovir resistance (93 [81%] of 115 patients with TAMs vs 352 [59%] of 597 patients without TAMs; p<0·0001), NNRTI resistance (107 [93%] vs 462 [77%]; p<0·0001), and cytosine analogue resistance (100 [87%] vs 378 [63%]; p=0·0002). We detected associations between TAMs and drug resistance mutations both between and within studies; the correlation between the study-level proportion of patients with tenofovir resistance and TAMs was 0·64 (p<0·0001), and the odds ratio for tenofovir resistance comparing patients with and without TAMs was 1·29 (1·13–1·47; p<0·0001)InterpretationTAMs are common in patients who have failure of first-line tenofovir-containing regimens in sub-Saharan Africa, and are associated with multidrug resistant HIV-1. Effective viral load monitoring and point-of-care resistance tests could help to mitigate the emergence and spread of such strains.

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Virological Response and Antiretroviral Drug Resistance Emerging during Antiretroviral Therapy at Three Treatment Centers in Uganda

Cited by 26 publications

References 17 publications

Factors Associated with Non-Adherence to Antiretroviral Treatment in Adults at Keetmanshoop District State Hospital in Namibia

Factors Associated with Non-Adherence to Antiretroviral Treatment in Adults at Keetmanshoop District State Hospital in Namibia

Lack of effectiveness of adherence counselling in reversing virological failure among patients on long‐term antiretroviral therapy in rural Uganda

Occult HIV-1 drug resistance to thymidine analogues following failure of first-line tenofovir combined with a cytosine analogue and nevirapine or efavirenz in sub Saharan Africa: a retrospective multi-centre cohort study

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