High Frequency of Antiretroviral Drug Resistance among HIV‐Infected Adults Receiving First‐Line Highly Active Antiretroviral Therapy in N’Djamena, Chad

Koyalta, Donato; Charpentier, Charlotte; Beassamda, Jatibi; Rey, Elisabeth; Si-Mohamed, Ali; Djemadji-Oudjeil, Noël; Bélec, Laurent

doi:10.1086/599611

Cited by 27 publications

(35 citation statements)

References 13 publications

(14 reference statements)

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“…Only Nigeria ( n = 183) and Cameroon ( n = 31) were represented by a high or relatively high number of sequences. Other western (Benin, Niger, and Togo) and central (Central African Republic, Chad, Equatorial Guinea, and Gabon) African countries with circulation of subtype G at significant levels (≥5% of all HIV-1 infections) [13], [14], [15], [16], [17], [67], [68], [69], [70], [71], [72] were represented by a small number of sequences ( n ≤15) that may not fully reflect the country’s subtype G diversity, or were not represented at all in our study (Fig. S2).…”

Section: Discussionmentioning

confidence: 99%

Spatiotemporal Dynamics of the HIV-1 Subtype G Epidemic in West and Central Africa

2014

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The human immunodeficiency virus type 1 (HIV-1) subtype G is the second most prevalent HIV-1 clade in West Africa, accounting for nearly 30% of infections in the region. There is no information about the spatiotemporal dynamics of dissemination of this HIV-1 clade in Africa. To this end, we analyzed a total of 305 HIV-1 subtype G pol sequences isolated from 11 different countries from West and Central Africa over a period of 20 years (1992 to 2011). Evolutionary, phylogeographic and demographic parameters were jointly estimated from sequence data using a Bayesian coalescent-based method. Our analyses indicate that subtype G most probably emerged in Central Africa in 1968 (1956–1976). From Central Africa, the virus was disseminated to West and West Central Africa at multiple times from the middle 1970s onwards. Two subtype G strains probably introduced into Nigeria and Togo between the middle and the late 1970s were disseminated locally and to neighboring countries, leading to the origin of two major western African clades (GWA-I and GWA-II). Subtype G clades circulating in western and central African regions displayed an initial phase of exponential growth followed by a decline in growth rate since the early/middle 1990s; but the mean epidemic growth rate of GWA-I (0.75 year−1) and GWA-II (0.95 year−1) clades was about two times higher than that estimated for central African lineages (0.47 year−1). Notably, the overall evolutionary and demographic history of GWA-I and GWA-II clades was very similar to that estimated for the CRF06_cpx clade circulating in the same region. These results support the notion that the spatiotemporal dissemination dynamics of major HIV-1 clades circulating in western Africa have probably been shaped by the same ecological factors.

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Section: Discussionmentioning

confidence: 99%

Spatiotemporal Dynamics of the HIV-1 Subtype G Epidemic in West and Central Africa

2014

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“…Currently, it is estimated that only 6,500 people have access ART. The high level of antiretroviral drug resistance in patients on first-line therapy clearly raises the issue of adequate HIV laboratory monitoring in Chad [27]. …”

Section: Methodsmentioning

confidence: 99%

Field evaluation in Chad of community usage of CD4 T lymphocyte counting by alternative single-platform flow cytometry

Koyalta¹,

Jenabian

Djouater

et al. 2013

BMC Health Serv Res

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BackgroundField and community evaluation of the routine usage of CD4 T counting platforms is essential in resource-poor countries for efficient and cost-effective monitoring of HIV-infected adults and children attending health care centers.MethodsWe herein addressed the principal issues raised by the implementation of the single-platform, volumetric Auto40 flow cytometer (Apogee Flow Systems Ltd, Hemel Hempstead, UK) in 8 community HIV monitoring laboratories of different levels throughout Chad. This is a country with particularly difficult conditions, both in terms of climate and vast geographical territory, making the decentralization of the therapeutic management of HIV-infected patients challenging.ResultsThe routine usage of the Auto40 flow cytometers for a period of 5 years (2008–2013) confirms the reliability and robustness of the analyzer for community-based CD4 T cell enumeration in terms of both absolute numbers and percentages to enable accurate monitoring of HIV-infected adults and children. However, our observations suggest that the Auto40 mini flow cytometer is not suitable for all laboratories as it is oversized and ultimately very expensive.ConclusionThe Chad experience with the Auto40 flow cytometer suggests that its usage in resource-limited settings should be mainly reserved to reference (level 1) or district (level 2) laboratories, rather than to laboratories of health care centres (level 3).

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“…To obtain estimates of rates and order of mutation accumulation of K65R and Q151M, descriptive statistical analyses of six publicly available data sets with genotypic drug resistance test (GRT) data of non-B subtype viruses from Sub-Saharan African settings were performed [13], [14], [25], [26], [27], [28]. Because the number of data points from first-line TDF use in resource-limited settings was very small (n = 24) in our sample, we additionally approximated rates of K65R and Q151M emergence from individuals failing first-line cART with D4T (along with lamivudine and an NNRTI), since this drug compound is also known to select for K65R and Q151M mutations and more data were available.…”

Section: Methodsmentioning

confidence: 99%

Cost-Effectiveness of Tenofovir Instead of Zidovudine for Use in First-Line Antiretroviral Therapy in Settings without Virological Monitoring

et al. 2012

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BackgroundThe most recent World Health Organization (WHO) antiretroviral treatment guidelines recommend the inclusion of zidovudine (ZDV) or tenofovir (TDF) in first-line therapy. We conducted a cost-effectiveness analysis with emphasis on emerging patterns of drug resistance upon treatment failure and their impact on second-line therapy.MethodsWe used a stochastic simulation of a generalized HIV-1 epidemic in sub-Saharan Africa to compare two strategies for first-line combination antiretroviral treatment including lamivudine, nevirapine and either ZDV or TDF. Model input parameters were derived from literature and, for the simulation of resistance pathways, estimated from drug resistance data obtained after first-line treatment failure in settings without virological monitoring. Treatment failure and cost effectiveness were determined based on WHO definitions. Two scenarios with optimistic (no emergence; base) and pessimistic (extensive emergence) assumptions regarding occurrence of multidrug resistance patterns were tested.ResultsIn the base scenario, cumulative proportions of treatment failure according to WHO criteria were higher among first-line ZDV users (median after six years 36% [95% simulation interval 32%; 39%]) compared with first-line TDF users (31% [29%; 33%]). Consequently, a higher proportion initiated second-line therapy (including lamivudine, boosted protease inhibitors and either ZDV or TDF) in the first-line ZDV user group 34% [31%; 37%] relative to first-line TDF users (30% [27%; 32%]). At the time of second-line initiation, a higher proportion (16%) of first-line ZDV users harboured TDF-resistant HIV compared with ZDV-resistant viruses among first-line TDF users (0% and 6% in base and pessimistic scenarios, respectively). In the base scenario, the incremental cost effectiveness ratio with respect to quality adjusted life years (QALY) was US$83 when TDF instead of ZDV was used in first-line therapy (pessimistic scenario: US$ 315), which was below the WHO threshold for high cost effectiveness (US$ 2154).ConclusionsUsing TDF instead of ZDV in first-line treatment in resource-limited settings is very cost-effective and likely to better preserve future treatment options in absence of virological monitoring.

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High Frequency of Antiretroviral Drug Resistance among HIV‐Infected Adults Receiving First‐Line Highly Active Antiretroviral Therapy in N’Djamena, Chad

Cited by 27 publications

References 13 publications

Spatiotemporal Dynamics of the HIV-1 Subtype G Epidemic in West and Central Africa

Spatiotemporal Dynamics of the HIV-1 Subtype G Epidemic in West and Central Africa

Field evaluation in Chad of community usage of CD4 T lymphocyte counting by alternative single-platform flow cytometry

Cost-Effectiveness of Tenofovir Instead of Zidovudine for Use in First-Line Antiretroviral Therapy in Settings without Virological Monitoring

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