Virological failure rates and HIV-1 drug resistance patterns in patients on first-line antiretroviral treatment in semirural and rural Gabon
28 Nov 2012-Journal of the International AIDS Society (The International AIDS Society)-Vol. 15, Iss: 2, pp 17985-17985
TL;DR: As antiretroviral treatment (ART) continues to expand in resource‐limited countries, the emergence of HIV drug resistance mutations (DRMs) is challenging in these settings.
Abstract: Introduction: As antiretroviral treatment (ART) continues to expand in resource-limited countries, the emergence of HIV drug resistance mutations (DRMs) is challenging in these settings. In Gabon (central Africa), no study has yet reported the virological effectiveness of initial ART given through routine HIV care. Methods: Following the World Health Organization (WHO) recommendations, a cross-sectional study with a one-time HIV-1 RNA viral load (VL) measurement was conducted in Gabon to assess virological failure (VF) defined by a VL result ≥1000 copies/ml and DRMs among adult patients living with non-B HIV-1 strains and receiving first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy for at least 12 months. Risk factors associated with VF and DRMs were assessed. Results: Between March 2010 and March 2011, a total of 375 patients were consecutively enrolled from two decentralized (one semirural and one rural) HIV care centres. Median time on ART was 33.6 months (range, 12-107). Overall, the rate of VF was 41.3% (36.4-46.4). Among viremic patients, 56.7% (80/141) had at least one DRM and 37.6% had dual-class resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and NNRTIs. The most frequent DRMs were K103N/S (46.1%) and M184V/I (37.6%). Thymidine analogue mutations were found in 10.6%. Independent risk factors associated with VF were being followed up at the semirural centre ( P =0.033), having experienced unstructured treatment interruptions ( P =0.0044), and having low CD4 counts at enrolment ( P <0.0001). A longer time on ART ( P =0.0008) and being followed up at the rural centre ( P =0.021) were risk factors for DRMs. Conclusions: This is the first study conducted in Gabon providing VF rates and DRM patterns in adult patients receiving first-line ART. In sub-Saharan Africa, where NNRTI-based regimens are recommended as the standard for first-line ART, strengthening virological monitoring together with preventing unplanned treatment interruptions are a global public health priority. Keywords: HIV; Africa; antiretroviral therapy; viral load; resistance. (Published: 28 November 2012) Citation: Liegeois F et al. Journal of the International AIDS Society 2012, 15 :17985 http://www.jiasociety.org/index.php/jias/article/view/17985 | http://dx.doi.org/10.7448/IAS.15.2.17985
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TL;DR: It was showed that patients aged <35 years and with recent low CD4 count, poor adherence to treatment, and longer exposure to ART were positively and significantly associated with virological treatment failure.
Abstract: BACKGROUND Viral load monitoring is used as an important biomarker for diagnosing treatment failure in patients with HIV infection/AIDS. Ethiopia has started targeted viral load monitoring. However, factors leading to virological failure are not well understood and studied. Thus, the aim of this study was to identify the determinants of virological failure among HIV-infected patients on highly active antiretroviral therapy at the University of Gondar Referral Hospital, Northwest Ethiopia. METHODS A case-control study was conducted from May to June 2015. Cases were subjects who had already experienced virological failure; controls were those without virological failure. Data were extracted from 153 cases and 153 controls through chart review. A multivariate logistic regression analysis was carried out to identify factors associated with virological failure, and variables with a p-value <0.05 were considered statistically significant. RESULTS In this study, higher odds of virological failure was observed among patients aged <35 years (adjusted odds ratio [AOR] =2.52, 95% CI: 1.33, 4.77), who had had CD4+ count <200 cells/mm3 (AOR=9.03, 95% CI: 4.40, 18.50), showed poor adherence to antiretroviral therapy (ART) (AOR=15.80, 95% CI: 6.90, 36.50), and had taken ART for longer durations of 25-47 months (AOR=3.00, 95% CI: 1.10, 8.40) and ≥48 months (AOR=6.70, 95% CI: 2.70, 16.60). CONCLUSION This study showed that patients aged <35 years and with recent low CD4 count, poor adherence to treatment, and longer exposure to ART were positively and significantly associated with virological treatment failure. Therefore, evidence-based intervention should be implemented to improve adherence to ART, which in turn helps to boost immunity (CD4) and suppresses viral replication and load. Moreover, attention should be given to younger patients who have had ART for longer periods.
49 citations
TL;DR: The data confirm that the currently recommended first-line ART regimen is efficient in the vast majority of individuals initiating therapy in Jimma, Ethiopia eight years after the introduction of ART, and underlines the need for rapid, inexpensive tests to identify the most common drug resistance mutations.
Abstract: Background
The ongoing scale-up of antiretroviral therapy (ART) in sub-Saharan Africa has prompted the interest in surveillance of transmitted and acquired HIV drug resistance. Resistance data on virological failure and mutations in HIV infected populations initiating treatment in sub-Saharan Africa is sparse.
41 citations
Cites result from "Virological failure rates and HIV-1..."
...Overall, the NRTI and NNRTI transmitted and acquired mutation patterns that were identified were consistent with previous reports in similar settings [19,24,25]....
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TL;DR: The accumulation of acquired HIVDR mutations in some participants underscores the need to reinforce HIVDR prevention strategies, such as increasing the availability and appropriate use of VL testing to monitor ART response, ensuring high quality adherence counseling, and promoting earlier identification of HIV patients and enrollment into HIV care and treatment programs.
Abstract: Treatment outcomes of HIV patients receiving antiretroviral therapy (ART) in Rwanda are scarcely documented. HIV viral load (VL) and HIV drug-resistance (HIVDR) outcomes at month 12 were determined in a prospective cohort study of antiretroviral–naive HIV patients initiating first-line therapy in Kigali. Treatment response was monitored clinically and by regular CD4 counts and targeted HIV viral load (VL) to confirm drug failure. VL measurements and HIVDR genotyping were performed retrospectively on baseline and month 12 samples. One hundred and fifty-eight participants who completed their month 12 follow-up visit had VL data available at month 12. Most of them (88%) were virologically suppressed (VL≤1000 copies/mL) but 18 had virological failure (11%), which is in the range of WHO-suggested targets for HIVDR prevention. If only CD4 criteria had been used to classify treatment response, 26% of the participants would have been misclassified as treatment failure. Pre-therapy HIVDR was documented in 4 of 109 participants (3.6%) with an HIVDR genotyping results at baseline. Eight of 12 participants (66.7%) with virological failure and HIVDR genotyping results at month 12 were found to harbor mutation(s), mostly NNRTI resistance mutations, whereas 4 patients had no HIVDR mutations. Almost half (44%) of the participants initiated ART at CD4 count ≤200cell/µl and severe CD4 depletion at baseline (<50 cells/µl) was associated with virological treatment failure (p = 0.008).
Although the findings may not be generalizable to all HIV patients in Rwanda, our data suggest that first-line ART regimen changes are currently not warranted. However, the accumulation of acquired HIVDR mutations in some participants underscores the need to reinforce HIVDR prevention strategies, such as increasing the availability and appropriate use of VL testing to monitor ART response, ensuring high quality adherence counseling, and promoting earlier identification of HIV patients and enrollment into HIV care and treatment programs.
35 citations
TL;DR: It was showed that low current CD4 T-cell count and body mass index, as well as poor adherence for ART treatment predicts virological failure, and deliberate efforts are urgently needed in HIV care through improving their nutritional status by enhancing nutritional education and support, and by strengthening enhanced adherence counseling.
Abstract: Virological treatment failure is a problem that a Human Immune Virus patient faces after starting treatment due to different factors. However, there were few studies done on the predictors of virological treatment failure among adult patients on first-line antiretroviral therapy in Ethiopia in general, and no study was done in the study area in particular. Therefore, the aim of the study was to identify predictors of virological treatment failure among adult patients on first-line antiretroviral therapy in Woldiya and Dessie Hospitals, Northeast Ethiopia. Hospital based case–control study was conducted in Woldia and Dessie Hospitals from from 12 August 2016–28 February 2018 on 154 cases and 154 controls among adult patients on first-line antiretroviral treatment. All cases were included and comparable controls were selected using stratified random sampling technique. Data were collected by document review using checklists and entered into Epidata version 3.1 and analyzed by SPSS version 21. Multivariable logistic regression analysis was done to identify the independent predictors of virological treatment failure. In this study, statistically higher odds of virological failure was observed among patients who had current CD4 T-cell count of 200 mm3, current body mass index(BMI) 18.5 kg/m2, BMI between 16 and 18.5 kg/m2 (AOR = 3.72, 95% CI: 1.75, 7.92) versus BMI > 18.5 kg/m2, poor adherence to antiretroviral therapy (AOR = 5.4, 95% CI: 2.95, 9.97) compared with good adherence. This study showed that low current CD4 T-cell count and body mass index, as well as poor adherence for ART treatment predicts virological failure. Therefore, deliberate efforts are urgently needed in HIV care through improving their nutritional status by enhancing nutritional education and support, and by strengthening enhanced adherence counseling.
34 citations
References
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TL;DR: Reports from resource-limited countries suggest that initial ART programmes are as effective as in resource-rich countries, which should limit HIV drug resistance if programme effectiveness continues during scale-up.
Abstract: Darunavir (TMC114) is a new HIV protease inhibitor that has demonstrated substantial antiretroviral activity against wild-type HIV-1 virus and multidrug-resistant strains Darunavir inhibits and is primarily metabolized by cytochrome P450 3A (CYP3A) isoenzymes and is coadministered with low-dose ritonavir (darunavir/r); ritonavir is an inhibitor of CYP3A isoenzymes and pharmacologically enhances darunavir, resulting in increased plasma concentrations and allowing for a lower daily dose The t1/2 (terminal elimination half-life) of darunavir is 15 h in the presence of ritonavir An extensive darunavir/r drug-drug interaction programme has been undertaken, covering a wide range of therapeutic areas Studies conducted in HIV-negative healthy volunteers and in HIV-infected patients show that the potential for interactions is well characterized and the interactions are manageable For most drugs investigated, no dose adjustments of darunavir/r or the co-administered drug are required This article reviews all the pharmacokinetic and drug-drug interaction studies conducted to date for darunavir/r, providing guidance on how to co-administer darunavir/r with many other antiretroviral or non-antiretroviral medications commonly used in HIV-infected individuals
305 citations
TL;DR: Profiles of drug resistance suggest that a second-line treatment regimen based on protease inhibitors, with a backbone of nucleoside reverse transcriptase inhibitor, is a reasonable option for patients with HIV in sub-Saharan Africa who experience first- line treatment failure.
Abstract: Following large-scale roll-out of antiretroviral therapy in sub-Saharan Africa, the non-clinical efficacy of antiretroviral therapy has received little attention. We aimed to systematically review virological efficacy and drug-resistance outcomes of programmes of antiretroviral therapy in sub-Saharan Africa. 89 studies with heterogeneous design, definitions, and methods were identified. Overall, in on-treatment analysis, 10 351 (78%) of 13 288 patients showed virological suppression after 6 months of antiretroviral therapy, 7413 (76%) of 9794 after 12 months, and 3840 (67%) of 5690 after 24 months. Long-term virological data are scarce. Genotyping results were available for patients with virological failure (HIV-1 RNA greater than 1000 copies per mL). Most patients (839 of 849; 99%) were infected with a non-B HIV-1 subtype. However, drug-resistance patterns were largely similar to those in subtype B. Resistance profiles were associated with the antiretroviral drugs commonly used: the lamivudine-associated M184V mutation was most common, followed by K103N which is associated with non-nucleoside reverse transcriptase inhibitors. Thymidine-analogue mutations and the K65R mutation were less common. First-line antiretroviral therapy regimens used in sub-Saharan Africa are effective. Profiles of drug resistance suggest that a second-line treatment regimen based on protease inhibitors, with a backbone of nucleoside reverse transcriptase inhibitors, is a reasonable option for patients with HIV in sub-Saharan Africa who experience first-line treatment failure.
299 citations
"Virological failure rates and HIV-1..." refers background in this paper
...In a review, Barth and colleagues reported virological success (defined by a VL B400 cp/ml) rates in sub-Saharan Africa of 78%, 76%, and 67% after 6, 12, and 24 months of ART, respectively [8]....
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TL;DR: When clinical and CD4 cell count criteria are used to monitor first-line ART failure, extensive nucleoside reverse transcriptase inhibitor and nonnucleoside Reverse Transcriptase inhibitor resistance emerges, with most patients having resistance profiles that markedly compromise the activity of second- line ART.
Abstract: BACKGROUND: Over 150000 Malawians have started antiretroviral therapy (ART) in which first-line therapy is stavudine/lamivudine/nevirapine. We evaluated drug resistance patterns among patients failing first-line ART on the basis of clinical or immunological criteria in Lilongwe and Blantyre Malawi. METHODS: Patients meeting the definition of ART failure (new or progressive stage 4 condition CD4 cell count decline more than 30% CD4 cell count less than that before treatment) from January 2006 to July 2007 were evaluated. Among those with HIV RNA of more than 1000 copies/ml genotyping was performed. For complex genotype patterns phenotyping was performed. RESULTS: Ninety-six confirmed ART failure patients were identified. Median (interquartile range) CD4 cell count log10 HIV-1 RNA and duration on ART were 68 cells/microl (23-174) 4.72 copies/ml (4.26-5.16) and 36.5 months (26.6-49.8) respectively. Ninety-three percent of samples had nonnucleoside reverse transcriptase inhibitor mutations and 81% had the M184V mutation. The most frequent pattern included M184V and nonnucleoside reverse transcriptase inhibitor mutations along with at least one thymidine analog mutation (56%). Twenty-three percent of patients acquired the K70E or K65R mutations associated with tenofovir resistance; 17% of the patients had pan-nucleoside resistance that corresponded to K65R or K70E and additional resistance mutations most commonly the 151 complex. Emergence of the K65R and K70E mutations was associated with CD4 cell count of less than 100 cells/microl (odds ratio 6.1) and inversely with the use of zidovudine (odds ratio 0.18). Phenotypic susceptibility data indicated that the nucleoside reverse transcriptase inhibitor backbone with the highest activity for subsequent therapy was zidovudine/lamivudine/tenofovir followed by lamivudine/tenofovir and then abacavir/didanosine. CONCLUSION: When clinical and CD4 cell count criteria are used to monitor first-line ART failure extensive nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor resistance emerges with most patients having resistance profiles that markedly compromise the activity of second-line ART.
291 citations