High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lomé, Togo
TL;DR: The high number of resistant strains observed in Togo shows clearly that the emergence of HIV drug resistance is of increasing concern in countries where ART is now widely used, and can compromise the long-term success of first- and second-line ART.
Abstract: With widespread use of antiretroviral (ARV) drugs in Africa, one of the major potential challenges is the risk of emergence of ARV drug-resistant HIV strains. Our objective is to evaluate the virological failure and genotypic drug-resistance mutations in patients receiving first-line highly active antiretroviral therapy (HAART) in routine clinics that use the World Health Organization public health approach to monitor antiretroviral treatment (ART) in Togo.
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TL;DR: The emergence of drug resistance following access to ART in resource-limited settings resembles what was seen inresource-rich countries and highlights the need for virological monitoring for drug failure, drug resistance testing and alternative drug regimens that have proven beneficial in these resource-rich settings.
Abstract: BackgroundThe increasing availability of antiretroviral therapy (ART) has improved survival and quality of life for many infected with HIV, but can also engender drug resistance. This review summar...
128 citations
TL;DR: The findings show heterogeneous virological failure and illustrate that, in addition to routine access to viral load, good management of ART programs is even more critical to improve treatment outcomes in resource-limited countries.
Abstract: Background The limited access to virological monitoring in developing countries is a major weakness of the current antiretroviral treatment (ART) strategy in these settings. We conducted a large cross-sectional study in Burkina Faso, Cameroon, Cote d'Ivoire, Senegal, Togo, Thailand, and Vietnam to assess virological failure and drug resistance mutations (DRMs) after 12 or 24 months of ART. Methods Between 2009 and 2011, we recruited adults attending ART centers 10-14 months (the M12 group) or 22-26 months (M24 group) after initiating ART. Demographic and clinical data were collected on site, and viral load was measured. Samples with a viral load of ≥ 1000 copies/mL, considered as the failure threshold, were genotyped for drug resistance assessment. Results Overall, 3935 patients were recruited (2060 at M12 and 1875 at M24). Median ages varied from 32 to 42 years. Median CD4(+) T-cell counts at ART initiation were low (99-172 cells/µL). The main ART regimens included stavudine/zidovudine plus lamivudine plus nevirapine/efavirenz. Overall, virological failure frequency was 11.1% for M12 patients and 12.4% for M24 patients, and 71.0% to 86.1% of these patients, respectively, had drug-resistant virus. Across sites, virological failure varied from 2.9% to 20.6% in M12 patients and from 3.7% to 26.0% in M24 patients. Predominant DRMs were associated with ART regimens, but virus in several patients accumulated DRMs to drugs not received, such as abacavir, didanosine, tenofovir, etravirine, and rilpivirine. Conclusions Our findings show heterogeneous virological failure and illustrate that, in addition to routine access to viral load, good management of ART programs is even more critical to improve treatment outcomes in resource-limited countries.
91 citations
TL;DR: The genetic diversity of HIV-1 continues to increase overtime due to demographic factors such as travel and migration and frequent co/superinfections, which leads to an increasing number of drug-resistant strains, especially in resource limited countries.
Abstract: HIV-1 in humans resulted from at least four cross-species transmissions of simian immunodeficiency viruses (SIVs) from chimpanzees and gorillas in West Central Africa, while HIV-2 viruses resulted from at least eight independent transmissions of SIVs infecting sooty mangabeys in West Africa only, where one of these transmissions (HIV-1 group M) is responsible for the global epidemic. HIV-1 M is subdivided into nine subtypes and a wide diversity of circulating recombinant forms (CRFs) and unique recombinant forms. The heterogenic HIV-1 M subtype/CRF distribution is the result of founder effects. The genetic diversity of HIV-1 continues to increase overtime due to demographic factors such as travel and migration and frequent co/superinfections. In addition, the expanded access to antiretrovirals leads to an increasing number of drug-resistant strains, especially in resource limited countries.
59 citations
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
56 citations
TL;DR: The low incidence rate of switching to second-line ART in sub-Saharan Africa suggests that the monitoring of patients under ART is challenging and that access to second -line ART is ineffective; efforts should be made to increase access toSecond- line ART to those in need by providing monitoring tools, education and training, as well as a more convenient regimen.
Abstract: OBJECTIVES Switching to second-line antiretroviral therapy (ART) largely depends on careful clinical assessment and access to biological measurements. We performed a systematic review and meta-analysis to estimate the incidence of switching to second-line ART in sub-Saharan Africa and its main programmatic determinants. METHODS We searched 2 databases for studies reporting the incidence rate of switching to second-line ART in adults living in sub-Saharan Africa. Data on the incidence rate of switching were pooled, and random-effect models were used to evaluate the effect of factors measured at the programme level on this incidence rate. RESULTS Nine studies (157,340 patients) in 21 countries were included in the meta-analysis. All studies considered patients under first-line ART and conditions to initiate ART were similar across studies. Overall, 3,736 (2.4%) patients switched to second-line ART. Incidence rate of switch was in mean 2.65 per 100 person-years (PY) (95% confidence interval: 2.01-3.30); it ranged from 0.42 to 4.88 per 100 PY and from 0 to 4.80 per 100 PY in programmes with and without viral load monitoring, respectively. No factors measured at the programme level were associated with the incidence rate of switching to second-line ART. CONCLUSION The low incidence rate of switching to second-line ART suggests that the monitoring of patients under ART is challenging and that access to second-line ART is ineffective; efforts should be made to increase access to second-line ART to those in need by providing monitoring tools, education and training, as well as a more convenient regimen.
51 citations
References
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TL;DR: The results support the safety and effectiveness of the triomune combination for first-line treatment of HIV infection and Virological effectiveness appeared to wane somewhat during the second year of treatment, however, and plasma nevirapine concentrations were relatively high.
Abstract: We assessed the long-term safety, effectiveness and quality of a fixed-dose combination of nevirapine, stavudine and lamivudine (triomune). HIV-1-infected adults initially enrolled in a one-year, open-label, single-arm, multicentre trial in Cameroon were followed for 2 years. Our results support the safety and effectiveness of the triomune combination for first-line treatment of HIV infection. Virological effectiveness appeared to wane somewhat during the second year of treatment, however, and plasma nevirapine concentrations were relatively high.
38 citations
"High prevalence of HIV-1 drug resis..." refers result in this paper
...Several cohort studies, using virological monitoring, have shown that ART treatment in resource-poor settings has efficacy rates similar to those reported for developed countries [7-12]....
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TL;DR: Among 128 patients routinely receiving highly active antiretroviral therapy in an HIV/AIDS outpatient clinic in Cameroon, 16.4% had drug resistance after a median of 10 months.
Abstract: Among 128 patients routinely receiving highly active antiretroviral therapy in an HIV/AIDS outpatient clinic in Cameroon, 16.4% had drug resistance after a median of 10 months. Of these, 12.5% had resistance to nucleoside reverse transcriptase inhibitors (NRTIs), 10.2% to non-NRTIs, and 2.3% to protease inhibitors.
34 citations
"High prevalence of HIV-1 drug resis..." refers result in this paper
...However, the few studies reporting on ART using the public health approach showed more contrasted results, with virological succes after 12 months ranging from 50% to more than 90% [13,14]....
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TL;DR: The complexity of the HIV-1 strains circulating in Togo is shown and a relative high proportion of ARV naive patients with drug-resistance mutations is documented.
29 citations
"High prevalence of HIV-1 drug resis..." refers background or methods or result in this paper
...HIV-1 subtypes/ CRFs were determined by phylogenetic tree and recombination analysis as previously decribed [6]....
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...In a previous study, we reported also that 10% of recently diagnosed ARV-naive HIV-1 positive patients in 2007 were infected with HIV strains that already harboured a drug-resistance mutation [6]....
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...However, the possibility cannot be excluded that some of the patients included in this and our previous study [6] were not ART naïve and already harboured ARV-resistant strains because this was based on self-reported information by the patients....
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