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1.
J Antimicrob Chemother ; 79(5): 1164-1168, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38546752

RESUMEN

OBJECTIVES: Integrase strand transfer inhibitors (INSTIs) have been recently recommended as the preferred first-line option for antiretroviral treatment initiators in low- and middle-income countries (LMICs) in response to the growing circulation of resistant HIV to non-nucleoside reverse transcriptase inhibitors (NNRTIs). In this study, we estimated the frequency of pretreatment drug resistance (PDR) to INSTIs in West Africa and Southeast Asia. MATERIALS AND METHODS: Using samples collected from 2015 to 2016, and previously used to assessed PI, NRTI and NNRTI resistance, we generated HIV integrase sequences and identified relevant INSTI PDR mutations using the Stanford and ANRS algorithms. RESULTS: We generated 353 integrase sequences. INSTI PDR frequency was low, 1.1% (4/353) overall, ranging from 0% to 6.3% according to country. However, frequency of PDR to any drug class was very high, 17.9% (95% CI: 13.9%-22.3%), and mostly associated with a high level of NNRTI PDR, 9.7%, and a moderate level of NRTI PDR, 5.3%. CONCLUSIONS: Our results support the recent introduction of INSTIs in LMICs to improve treatment outcome in these settings, but also stress the need for effective actions to prevent uncontrolled emergence of drug resistance to this drug class.


Asunto(s)
Farmacorresistencia Viral , Infecciones por VIH , Inhibidores de Integrasa VIH , Integrasa de VIH , VIH-1 , Humanos , África Occidental/epidemiología , Asia Sudoriental/epidemiología , Farmacorresistencia Viral/genética , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Infecciones por VIH/epidemiología , Integrasa de VIH/genética , Inhibidores de Integrasa VIH/farmacología , Inhibidores de Integrasa VIH/uso terapéutico , VIH-1/efectos de los fármacos , VIH-1/genética , Mutación , Prevalencia
2.
J Antimicrob Chemother ; 78(12): 2938-2942, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37921335

RESUMEN

OBJECTIVES: To characterize HIV drug resistance (HIVDR) below and above the WHO threshold of 1000 copies/mL, considered for the definition of HIV ART failure in resource-limited settings. METHODS: From a cohort of 280 adolescents (aged 10-19 years) receiving ART for at least 6 months, genotypic resistance testing (GRT) was attempted for two groups of participants: participants with low-level viraemia [LLV; viral load (VL) 200-999 copies/mL] and those in virological failure (VF; confirmed VL ≥1000 copies/mL) using an in-house method. The Stanford HIValg Program was used to identify relevant HIVDR mutations and predict the efficacy of the newly introduced tenofovir-lamivudine-dolutegravir combination. RESULTS: GRT was successfully performed in 54/58 (93.1%) eligible participants, of which 28/31 (90.3%) were in VF and 26/27 (96.3%) had LLV. A high level of resistance was found both in adolescents with LLV and those in VF, with respectively 84.6% (22/26) and 75.0% (21/28) of participants harbouring at least one HIVDR mutation. NRTIs and NNRTIs were the most affected drug classes in both population groups. In contrast, PIs were not significantly affected and dolutegravir was expected to be active for all participants tested. However, for the newly introduced dolutegravir-based combination, functional monotherapy (dolutegravir only) was potentially possible for 22.7% (5/22) of the participants with LLV. CONCLUSIONS: Our findings show that the 1000 copies/mL threshold is not an indicator of virological success and we call for a revision of the current WHO definition of VF in resource-limited countries.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Humanos , Adolescente , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/farmacología , Viremia/tratamiento farmacológico , Viremia/epidemiología , Camerún/epidemiología , Prevalencia , VIH-1/genética , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Carga Viral , Farmacorresistencia Viral/genética
3.
BMC Pediatr ; 23(1): 119, 2023 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-36922769

RESUMEN

BACKGROUND: Achieving the UNAIDS 95% sustained viral suppression (VS) rate requires considerable global efforts, particularly among adolescents living with HIV (ALHIV) who are often associated with high rates of virological failure (VF). In this study, we prospectively assessed the rate of VS, and the factors associated with VF in a cohort of adolescents followed up according to the WHO guidelines in Cameroon. METHODS: A cross-sectional study was carried out in 2021 among adolescents (aged 10-19 years) receiving ART in the national program in Cameroon. Socio-demographic and clinical data were collected using patients' medical files and a brief interview with the participant and/or his guardian. Thereafter, a first viral load test (VL1) was performed using the ABBOTT Platform. For adolescents with VL1 > 1000 copies/ml, adherence-enhancing interventions were routinely performed each month for 3 consecutive months, after which a second viral load (VL2) was measured. Adolescents with VL2 > 1000 copies/ml were considered in VF. RESULTS: Overall, 280 adolescents were enrolled, of whom 89.3% (250/280) acquired HIV infection via mother-to-child transmission. The median age was 16.0 (IQR: 13.0-18.0) years and the median duration on ART was 9.8 (IQR: 5.1-12.8) years. Females and males were almost equally represented, as 52.1% (146/280) were female, while 47.9% (134/280) were males (p = 0.47). The VS rate was 88.2% (CI: 83.8-91.7%) overall; 89.0% (CI: 82.0-93.1%) and 88.7% (CI: 81.2-93.0%) in females and males, respectively. Being on second or third-line ART, self-declared suboptimal adherence, and a history of past VF were independently associated with VF. CONCLUSION: The high rate of VS we report in this study is welcome in the era of the 95/95/95 UNAIDS goals, and indicates that improving treatment outcomes in this specific and fragile population that represent adolescents in Sub-Saharan Africa is achievable. TRIAL REGISTRATION: 20/10/2020 NCT04593979 ( https://clinicaltrials.gov/ct2/show/NCT04593979 ).


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Masculino , Humanos , Femenino , Adolescente , Infecciones por VIH/epidemiología , Carga Viral , Camerún/epidemiología , Estudios Transversales , Transmisión Vertical de Enfermedad Infecciosa , Fármacos Anti-VIH/uso terapéutico
4.
J Antimicrob Chemother ; 76(4): 1051-1056, 2021 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-33367796

RESUMEN

BACKGROUND: The projected UNAIDS goal of ending AIDS by 2030 requires significant global efforts to improve current and future ART strategies. In this study, we assessed viral load (VL) suppression and acquired drug resistance, as well as future efficacy of dolutegravir-based combinations for patients living in semi-rural regions of Gabon. METHODS: Eligible study participants were adults receiving ART and recruited between 2018 and 2019 in Franceville, Gabon. VL testing was conducted to assess VL suppression and HIV drug resistance (HIVDR) testing was performed to identify resistance mutations and assess their impact on ongoing and future ART regimens. RESULTS: We recruited 219 participants overall. The median time on ART was 27 months and 216/219 participants were on first-line ART. VL suppression (VL < 1000 copies/mL) was 57.1% (95% CI 50.5-63.8) overall; 59.4% (51.4-67.5) and 52.2% (40.3-64.2) for women and men, respectively. The overall prevalence of HIVDR was 21.9% among the study population and 67.2% among those who failed ART. Presence of both NRTI and NNRTI mutations was found in 84.6% of sequences with drug resistance mutations, and full activity of a dolutegravir-based first-line regimen including tenofovir disoproxil fumarate/lamivudine/dolutegravir was expected only for 5/39 patients with a resistant virus. CONCLUSIONS: This study shows a very low rate of VL suppression in a semi-rural context in Africa. Moreover, the high burden of HIVDR has affected both current and newly recommended ART strategies. Better management of ART in resource-limited settings is still a challenging ambition.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Adulto , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéutico , Resistencia a Medicamentos , Farmacorresistencia Viral , Femenino , Gabón/epidemiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Compuestos Heterocíclicos con 3 Anillos , Humanos , Masculino , Oxazinas , Piperazinas , Piridonas , Carga Viral
5.
Clin Infect Dis ; 70(7): 1471-1477, 2020 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-31063537

RESUMEN

BACKGROUND: Little is known about impact of genetic divergence of human immunodeficiency virus type 1 group O (HIV-1/O) relative to HIV-1 group M (HIV-1/M) on therapeutic outcomes. We aimed to determine if responses to standardized combination antiretroviral therapy (cART) were similar between groups despite strain divergence. METHODS: We performed an open nonrandomized study comparing the immunological, virological, and clinical responses to cART based on 2 nucleoside reverse transcriptase inhibitors plus 1 ritonavir-boosted protease inhibitor, in naive and paired HIV-1/O vs HIV-1/M infected (+) patients (ratio 1:2), matched on several criteria. The primary endpoint was the proportion of patients with undetectable plasma viral load (pVL, threshold 60 copies/mL) at week (W) 48. Secondary endpoints were the proportion of patients with undetectable pVL at W24 and W96 and CD4 evolution between baseline and W24, W48, and W96. RESULTS: Forty-seven HIV-1/O+ and 94 HIV-1/M+ patients were included. Mean pVL at baseline was significantly lower by 1 log for HIV-1/O+ vs HIV-1/M+ patients. At W48, no significant difference was observed between populations with undetectable pVL and differences at W24 and W96 were not significant. A difference in CD4 gain was observed in favor of HIV-1/M at W48 and W96, but this was not significant when adjusted on both matched criteria and pVL at baseline. CONCLUSIONS: Our data demonstrate similar immunovirological and clinical response between HIV-1/O+ and HIV-1/M+ patients. They also reveal significantly lower baseline replication for HIV-1/O variants, suggesting specific virological properties and physiopathology that now need to be addressed. CLINICAL TRIALS REGISTRATION: NCT00658346.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Fármacos Anti-VIH/uso terapéutico , Antirretrovirales/uso terapéutico , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Quimioterapia Combinada , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , Humanos , Ritonavir/uso terapéutico , Carga Viral
6.
J Antimicrob Chemother ; 74(2): 462-467, 2019 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-30418575

RESUMEN

Background: ART in the developing world has moved to a new era with the WHO recommendation to test and immediately treat HIV-positive individuals. A high frequency of pretreatment HIV drug resistance (PDR) can compromise ART efficacy. Our study presents updated estimates of PDR in seven countries from West Africa (Burkina Faso, Cameroon, Côte d'Ivoire, Mali and Togo) and Southeast Asia (Thailand and Vietnam). Methods: Eligible study participants were adult ART initiators, recruited from December 2015 to November 2016 in major ART clinics in each country. HIV drug resistance (HIVDR) tests were performed for all specimens and interpretation was done using the Stanford algorithm. Results: Overall, 1153 participants were recruited and 1020 nt sequences were generated. PDR frequency among all initiators was 15.9% (95% CI: 13.8%-18.3%) overall, ranging from 9.6% and 10.2% in Burkina Faso and Thailand, respectively, 14.7% in Vietnam, 15.4% in Mali, 16.5% in Côte d'Ivoire and 19.3% in Cameroon, to 24.6% in Togo. The prevalence of NNRTI resistance mutations was 12%; NRTI and PI PDR prevalences were 4% and 3%, respectively. Conclusions: Our study shows that in most countries PDR exceeded 10%, warranting the conduct of nationally representative surveys to confirm this trend. In the meantime, actions to prevent drug resistance, including transition from NNRTIs to more robust drug classes should be urgently implemented.


Asunto(s)
Farmacorresistencia Viral/genética , Infecciones por VIH/epidemiología , VIH-1/efectos de los fármacos , Adulto , África Occidental/epidemiología , Fármacos Anti-VIH/sangre , Asia Sudoriental/epidemiología , Femenino , VIH-1/genética , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Carga Viral
7.
J Antimicrob Chemother ; 73(9): 2468-2474, 2018 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-29931063

RESUMEN

Background: Pretreatment HIV drug resistance (PDR) has the potential to affect treatment outcome and mortality. We present here the first nationally representative PDR study conducted in Cameroon. Methods: From February to July 2015, HIV-infected ART initiators were recruited from 24 randomly selected clinics situated in both urban and rural regions. Dried blood spot specimens were collected from study participants at these clinics and centralized in a reference laboratory in Yaoundé, Cameroon, for drug resistance testing. HIV drug resistance mutations were identified using the Stanford algorithm. Results: Overall, from the 379 participants recruited, 321 pol sequences were successfully interpreted. Two hundred and five sequences were from patients attending urban ART clinics and 116 from patients seen at rural facilities. Nine percent of sequences (29/321) were from participants reporting previous exposure to antiretrovirals. PDR prevalence among all initiators was 10.4% (95% CI 5.4%-19.1%), with 14.2% (95% CI 6.6%-27.9%) reported in urban areas and 4.3% (95% CI 1.2%-14.3%) in rural areas. Among participants with no prior exposure to antiretrovirals, PDR prevalence was 10.4% (95% CI 4.7%-21.5%) overall, with 13.5% (95% CI 5.1%-31.5%) and 5.3% (95% CI 1.4%-17.5%) reported in urban and rural areas, respectively. Conclusions: Our findings indicate that at least 10% of patients initiating ART in Cameroon carry viruses with PDR and may be at risk of premature ART failure. The high level of NNRTI-associated resistance is of particular concern and supports introduction of drugs with a higher genetic barrier to resistance.


Asunto(s)
Farmacorresistencia Viral , Infecciones por VIH/virología , VIH/efectos de los fármacos , Adolescente , Adulto , Sangre/virología , Camerún/epidemiología , Femenino , Genotipo , Técnicas de Genotipaje , VIH/genética , Infecciones por VIH/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Población Rural , Población Urbana , Adulto Joven
8.
J Virol ; 91(6)2017 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-28077632

RESUMEN

Human immunodeficiency virus type 1 (HIV-1) is the result of cross-species transmission of simian immunodeficiency virus from chimpanzees (SIVcpz). SIVcpz is a chimeric virus which shares common ancestors with viruses infecting red-capped mangabeys and a subset of guenon species. The epidemiology of SIV infection in hominoids is characterized by low prevalences and an uneven geographic distribution. Surveys in Cameroon indicated that two closely related members of the guenon species subset, mustached guenons and greater spot-nosed guenons, infected with SIVmus and SIVgsn, respectively, also have low rates of SIV infections in their populations. Compared to that for other monkeys, including red-capped mangabeys and closely related guenon species, such an epidemiology is unusual. By intensifying sampling of geographically distinct populations of mustached and greater spot-nosed guenons in Gabon and including large sample sets of mona guenons from Cameroon, we add strong support to the hypothesis that the paucity of SIV infections in wild populations is a general feature of this monophyletic group of viruses. Furthermore, comparative phylogenetic analysis reveals that this phenotype is a feature of this group of viruses infecting phylogenetically disparate hosts, suggesting that this epidemiological phenotype results from infection with these HIV-1-related viruses rather than from a common host factor. Thus, these HIV-1-related viruses, i.e., SIVcpz and the guenon viruses which share an ancestor with part of the SIVcpz genome, have an epidemiology distinct from that found for SIVs in other African primate species.IMPORTANCE Stable virus-host relationships are established over multiple generations. The prevalence of viral infections in any given host is determined by various factors. Stable virus-host relationships of viruses that are able to cause persistent infections and exist with high incidences of infection are generally characterized by a lack of morbidity prior to host reproduction. Such is the case for cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections of humans. SIV infections of most African primate species also satisfy these criteria, with these infections found at a high prevalence and with rare cases of clinical disease. In contrast, SIVcpz, the ancestor of HIV-1, has a different epidemiology, and it has been reported that infected animals suffer from an AIDS-like disease in the wild. Here we conclusively demonstrate that viruses which are closely related to SIVcpz and infect a subset of guenon monkeys show an epidemiology resembling that of SIVcpz.


Asunto(s)
Variación Genética , Filogeografía , Síndrome de Inmunodeficiencia Adquirida del Simio/epidemiología , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Virus de la Inmunodeficiencia de los Simios/clasificación , Virus de la Inmunodeficiencia de los Simios/genética , Topografía Médica , Animales , Camerún , Gabón , Haplorrinos , Prevalencia , Virus de la Inmunodeficiencia de los Simios/aislamiento & purificación
10.
PLoS Med ; 12(4): e1001810, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25849352

RESUMEN

BACKGROUND: Regional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes. METHODS AND FINDINGS: We reviewed all GenBank submissions of HIV-1 reverse transcriptase sequences with or without protease and identified 287 studies published between March 1, 2000, and December 31, 2013, with more than 25 recently or chronically infected ARV-naïve individuals. These studies comprised 50,870 individuals from 111 countries. Each set of study sequences was analyzed for phylogenetic clustering and the presence of 93 surveillance drug-resistance mutations (SDRMs). The median overall TDR prevalence in sub-Saharan Africa (SSA), south/southeast Asia (SSEA), upper-income Asian countries, Latin America/Caribbean, Europe, and North America was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%, and 11.5%, respectively. In SSA, there was a yearly 1.09-fold (95% CI: 1.05-1.14) increase in odds of TDR since national ARV scale-up attributable to an increase in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. The odds of NNRTI-associated TDR also increased in Latin America/Caribbean (odds ratio [OR] = 1.16; 95% CI: 1.06-1.25), North America (OR = 1.19; 95% CI: 1.12-1.26), Europe (OR = 1.07; 95% CI: 1.01-1.13), and upper-income Asian countries (OR = 1.33; 95% CI: 1.12-1.55). In SSEA, there was no significant change in the odds of TDR since national ARV scale-up (OR = 0.97; 95% CI: 0.92-1.02). An analysis limited to sequences with mixtures at less than 0.5% of their nucleotide positions­a proxy for recent infection­yielded trends comparable to those obtained using the complete dataset. Four NNRTI SDRMs­K101E, K103N, Y181C, and G190A­accounted for >80% of NNRTI-associated TDR in all regions and subtypes. Sixteen nucleoside reverse transcriptase inhibitor (NRTI) SDRMs accounted for >69% of NRTI-associated TDR in all regions and subtypes. In SSA and SSEA, 89% of NNRTI SDRMs were associated with high-level resistance to nevirapine or efavirenz, whereas only 27% of NRTI SDRMs were associated with high-level resistance to zidovudine, lamivudine, tenofovir, or abacavir. Of 763 viruses with TDR in SSA and SSEA, 725 (95%) were genetically dissimilar; 38 (5%) formed 19 sequence pairs. Inherent limitations of this study are that some cohorts may not represent the broader regional population and that studies were heterogeneous with respect to duration of infection prior to sampling. CONCLUSIONS: Most TDR strains in SSA and SSEA arose independently, suggesting that ARV regimens with a high genetic barrier to resistance combined with improved patient adherence may mitigate TDR increases by reducing the generation of new ARV-resistant strains. A small number of NNRTI-resistance mutations were responsible for most cases of high-level resistance, suggesting that inexpensive point-mutation assays to detect these mutations may be useful for pre-therapy screening in regions with high levels of TDR. In the context of a public health approach to ARV therapy, a reliable point-of-care genotypic resistance test could identify which patients should receive standard first-line therapy and which should receive a protease-inhibitor-containing regimen.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Secuencia de Bases , Farmacorresistencia Viral , Infecciones por VIH/tratamiento farmacológico , Transcriptasa Inversa del VIH/genética , VIH-1/genética , Mutación , África , Américas , Fármacos Anti-VIH/farmacología , Asia , Europa (Continente) , Infecciones por VIH/virología , Transcriptasa Inversa del VIH/antagonistas & inhibidores , VIH-1/efectos de los fármacos , Humanos , Epidemiología Molecular , Filogenia
11.
Clin Infect Dis ; 58(1): 99-109, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24076968

RESUMEN

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.


Asunto(s)
Antirretrovirales/uso terapéutico , Terapia Antirretroviral Altamente Activa/métodos , Infecciones por VIH/tratamiento farmacológico , Adulto , África del Sur del Sahara , Asia Sudoriental , Estudios Transversales , Monitoreo de Drogas , Farmacorresistencia Viral , Femenino , VIH/genética , VIH/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , ARN Viral/genética , Análisis de Secuencia de ADN , Resultado del Tratamiento , Carga Viral
12.
J Clin Microbiol ; 52(2): 578-86, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24478491

RESUMEN

Dried blood spots (DBS) can be used in developing countries to alleviate the logistic constraints of using blood plasma specimens for viral load (VL) and HIV drug resistance (HIVDR) testing, but they should be assessed under field conditions. Between 2009 and 2011, we collected paired plasma-DBS samples from treatment-experienced HIV-1-infected adults in Burkina Faso, Cameroon, Senegal, Togo, Thailand, and Vietnam. The DBS were stored at an ambient temperature for 2 to 4 weeks and subsequently at -20°C before testing. VL testing was performed on the plasma samples and DBS using locally available methods: the Abbott m2000rt HIV-1 test, generic G2 real-time PCR, or the NucliSENS EasyQ version 1.2 test. In the case of virological failure (VF), i.e., a plasma VL of ≥1,000 copies/ml, HIVDR genotyping was performed on paired plasma-DBS samples. Overall, we compared 382 plasma-DBS sample pairs for DBS VL testing accuracy. The sensitivities of the different assays in different laboratories for detecting VF using DBS varied from 75% to 100% for the m2000rt test in labs B, C, and D, 91% to 93% for generic G2 real-time PCR in labs A and F, and 85% for the NucliSENS test in lab E. The specificities varied from 82% to 97% for the m2000rt and NucliSENS tests and reached only 60% for the generic G2 test. The NucliSENS test showed good agreement between plasma and DBS VL but underestimated the DBS VL. The lowest agreement was observed for the generic G2 test. Genotyping was successful for 96/124 (77%) DBS tested, and 75/96 (78%) plasma-DBS pairs had identical HIVDR mutations. Significant discrepancies in resistance interpretations were observed in 9 cases, 6 of which were from the same laboratory. DBS can be successfully used as an alternative to blood plasma samples for routine VL and HIVDR monitoring in African and Asian settings. However, the selection of an adequate VL measurement method and the definition of the VF threshold should be considered, and laboratory performance should be monitored.


Asunto(s)
Sangre/virología , Desecación , Infecciones por VIH/diagnóstico , VIH-1/efectos de los fármacos , VIH-1/aislamiento & purificación , Manejo de Especímenes/métodos , Carga Viral/métodos , Adolescente , Adulto , África , Anciano , Anciano de 80 o más Años , Terapia Antirretroviral Altamente Activa/métodos , Asia , Estudios Transversales , Femenino , Genotipo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Humanos , Masculino , Pruebas de Sensibilidad Microbiana/métodos , Persona de Mediana Edad , Sensibilidad y Especificidad , Temperatura , Factores de Tiempo , Adulto Joven
13.
J Infect Dis ; 207 Suppl 2: S70-7, 2013 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-23687292

RESUMEN

BACKGROUND: The World Health Organization Antiretroviral Treatment Guidelines recommend phasing-out stavudine because of its risk of long-term toxicity. There are two mutational pathways of stavudine resistance with different implications for zidovudine and tenofovir cross-resistance, the primary candidates for replacing stavudine. However, because resistance testing is rarely available in resource-limited settings, it is critical to identify the cross-resistance patterns associated with first-line stavudine failure. METHODS: We analyzed HIV-1 resistance mutations following first-line stavudine failure from 35 publications comprising 1,825 individuals. We also assessed the influence of concomitant nevirapine vs. efavirenz, therapy duration, and HIV-1 subtype on the proportions of mutations associated with zidovudine vs. tenofovir cross-resistance. RESULTS: Mutations with preferential zidovudine activity, K65R or K70E, occurred in 5.3% of individuals. Mutations with preferential tenofovir activity, ≥ two thymidine analog mutations (TAMs) or Q151M, occurred in 22% of individuals. Nevirapine increased the risk of TAMs, K65R, and Q151M. Longer therapy increased the risk of TAMs and Q151M but not K65R. Subtype C and CRF01_AE increased the risk of K65R, but only CRF01_AE increased the risk of K65R without Q151M. CONCLUSIONS: Regardless of concomitant nevirapine vs. efavirenz, therapy duration, or subtype, tenofovir was more likely than zidovudine to retain antiviral activity following first-line d4T therapy.


Asunto(s)
Antirretrovirales/administración & dosificación , Farmacorresistencia Viral , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , ARN Viral/análisis , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Adenina/administración & dosificación , Adenina/análogos & derivados , Alquinos , Benzoxazinas/administración & dosificación , Ciclopropanos , Bases de Datos Factuales , Farmacorresistencia Viral/genética , Quimioterapia Combinada , Genotipo , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , VIH-1/fisiología , Humanos , Mutación Missense , Nevirapina/administración & dosificación , Organofosfonatos/administración & dosificación , ARN Viral/genética , Estavudina/administración & dosificación , Tenofovir , Zidovudina/administración & dosificación
14.
Clin Infect Dis ; 57(4): 604-7, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23667264

RESUMEN

Our study in Cameroonian rural district hospitals showed that the immunologic and clinical failure criteria had poor performance to identify human immunodeficiency virus drug resistance in a timely manner. Switching to second-line antiretroviral therapy after 2 consecutive viral loads ≥5000 copies/mL, as recommended by the World Health Organization, appeared to be the most appropriate strategy.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Técnicas de Apoyo para la Decisión , Farmacorresistencia Viral , Infecciones por VIH/tratamiento farmacológico , Cumplimiento de la Medicación/estadística & datos numéricos , Carga Viral , Adulto , Recuento de Linfocito CD4 , Camerún , Femenino , Infecciones por VIH/inmunología , Infecciones por VIH/patología , Infecciones por VIH/virología , Hospitales , Humanos , Masculino , Persona de Mediana Edad , Población Rural
15.
J Clin Microbiol ; 51(3): 787-98, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23254130

RESUMEN

Although antiretroviral treatment availability has improved, the virological monitoring of patients remains largely uneven across regions. In addition, viral quantification tests are suffering from human immunodeficiency virus type 1 (HIV-1) genetic diversity, fueled by the emergence of new recombinants and of lentiviruses from nonhuman primates. We developed a real-time reverse transcription-PCR (RT-PCR) assay that is relatively inexpensive and able to detect and quantify all circulating forms of HIV-1 and its simian immunodeficiency virus (SIV) precursors, SIVcpz and SIVgor. Primers and a probe were designed to detect all variants of the HIV-1/SIVcpz/SIVgor lineage. HIV-1 M plasma (n = 190; 1.68 to 7.78 log(10) copies/ml) representing eight subtypes, nine circulating recombinant forms, and 21 unique recombinant forms were tested. The mean PCR efficiency was 99%, with low coefficients of intra- and interassay variation (<5%) and a limit of quantification of <2.50 log(10) copies/ml, with a 200-µl plasma volume. On the studied range, the specificity and the analytical sensitivity were 100 and 97.4%, respectively. The viral loads were highly correlated (r = 0.95, P < 0.0001) with the reference method (generic HIV assay; Biocentric) and had no systematic difference, irrespective of genotype. Furthermore, 22 HIV-1 O plasmas were screened and were better quantified compared to the gold-standard RealTime HIV-1 assay (Abbott), including four samples that were only quantified by our assay. Finally, we could quantify SIVcpzPtt and SIVcpzPts from chimpanzee plasma (n = 5) and amplify SIVcpz and SIVgor from feces. Thus, the newly developed real-time RT-PCR assay detects and quantifies strains from the HIV-1/SIVcpz/SIVgor lineage, including a wide diversity of group M strains and HIV-1 O. It can therefore be useful in geographical areas of high HIV diversity and at risk for the emergence of new HIV variants.


Asunto(s)
VIH-1/clasificación , VIH-1/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Virus de la Inmunodeficiencia de los Simios/clasificación , Virus de la Inmunodeficiencia de los Simios/genética , Carga Viral/métodos , Animales , Cartilla de ADN/genética , Heces/virología , Humanos , Sondas de Oligonucleótidos/genética , Pan troglodytes , Plasma/virología , Sensibilidad y Especificidad
16.
J Virol ; 86(18): 9760-72, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22740419

RESUMEN

Simian immunodeficiency viruses infecting western lowland gorillas (SIVgor) are closely related to HIV-1 and are most likely the ancestors of HIV-1 groups O and P. At present, limited data are available on genetic diversity, transmission, viral evolution, and pathogenicity of SIVgor in its natural host. Between 2004 and 2011, 961 putative gorilla fecal samples were collected at the Campo Ma'an National Park, Cameroon. Among them, 16% cross-reacted with HIV-1 antibodies, corresponding to at least 34 infected gorillas. Combining host genotyping and field data, we identified four social groups composed of 7 to 15 individuals each, with SIV rates ranging from 13% to 29%. Eleven SIVgor-infected gorillas were sampled multiple times; two most likely seroconverted during the study period, showing that SIVgor continues to spread. Phylogenetic analysis of partial env and pol sequences revealed cocirculation of closely related and divergent strains among gorillas from the same social group, indicating SIVgor transmissions within and between groups. Parental links could be inferred for some gorillas infected with closely related strains, suggesting vertical transmission, but horizontal transmission by sexual or aggressive behavior was also suspected. Intrahost molecular evolution in one gorilla over a 5-year period showed viral adaptations characteristic of escape mutants, i.e., V1V2 loop elongation and an increased number of glycosylation sites. Here we show for the first time the feasibility of noninvasive monitoring of nonhabituated gorillas to study SIVgor infection over time at both the individual and population levels. This approach can also be applied more generally to study other pathogens in wildlife.


Asunto(s)
Gorilla gorilla , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Virus de la Inmunodeficiencia de los Simios/genética , Animales , Animales Salvajes/inmunología , Animales Salvajes/virología , Anticuerpos Antivirales/análisis , Secuencia de Bases , Camerún , ADN Viral/genética , Transmisión de Enfermedad Infecciosa/veterinaria , Heces/química , Femenino , Estudios de Seguimiento , Genes env , Genes pol , Variación Genética , Gorilla gorilla/inmunología , Gorilla gorilla/virología , VIH-1/genética , Interacciones Huésped-Patógeno , Transmisión Vertical de Enfermedad Infecciosa/veterinaria , Masculino , Glicoproteínas de Membrana/genética , Datos de Secuencia Molecular , Filogenia , Embarazo , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/transmisión , Virus de la Inmunodeficiencia de los Simios/clasificación , Virus de la Inmunodeficiencia de los Simios/inmunología , Proteínas del Envoltorio Viral/genética
17.
BMC Public Health ; 13: 308, 2013 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-23565992

RESUMEN

BACKGROUND: Rapid scale-up of antiretroviral therapy (ART) and limited access to genotyping assays in low-resource settings (LRS) are inevitably accompanied by an increasing risk of HIV drug resistance (HIVDR). The current study aims to evaluate early warning indicators (EWI) as an efficient strategy to limit the development and spread of preventable HIVDR in these settings, in order to sustain the performance of national antiretroviral therapy (ART) rollout programmes. METHODS: Surveys were conducted in 2008, 2009 and 2010 within 10 Cameroonian ART clinics, based on five HIVDR EWIs: (1) Good prescribing practices; (2) Patient lost to follow-up; (3) Patient retention on first line ART; (4) On-time drug pick-up; (5) Continuous drug supply. Analysis was performed as per the World Health Organisation (WHO) protocol. RESULTS: An overall decreasing performance of the national ART programme was observed from 2008 to 2010: EWI(1) (100% to 70%); EWI(2) (40% to 20%); EWI(3) (70% to 0%); EWI(4) (0% throughout); EWI(5) (90% to 40%). Thus, prescribing practices (EWI(1)) were in conformity with national guidelines, while patient adherence (EWI(2), EWI(3), and EWI(4)) and drug supply (EWI(5)) were lower overtime; with a heavy workload (median ratio ≈1/64 staff/patients) and community disengagement observed all over the study sites. CONCLUSIONS: In order to limit risks of HIVDR emergence in poor settings like Cameroon, continuous drug supply, community empowerment to support adherence, and probably a reduction in workload by task shifting, are the potential urgent measures to be undertaken. Such evidence-based interventions, rapidly generated and less costly, would be relevant in limiting the spread of preventable HIVDR and in sustaining the performance of ART programmes in LRS.


Asunto(s)
Antirretrovirales/farmacología , Farmacorresistencia Viral , Infecciones por VIH/tratamiento farmacológico , Indicadores de Salud , Vigilancia de la Población/métodos , Antirretrovirales/provisión & distribución , Antirretrovirales/uso terapéutico , Camerún , Países en Desarrollo , Humanos , Perdida de Seguimiento , Cumplimiento de la Medicación/estadística & datos numéricos , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/estadística & datos numéricos , Evaluación de Programas y Proyectos de Salud
18.
IJID Reg ; 9: 32-37, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37841692

RESUMEN

Objectives: Hepatitis B virus (HBV) infection remains a public health threat in middle- and low-income countries, where mother-to-child transmission plays an important role. The aim of this study was to assess the burden of this infection among pregnant women in southern Gabon and the risk of vertical transmission. Methods: The study was a prospective investigation conducted from April 2021 to January 2022. Study participants were pregnant women aged 18 and over attending antenatal clinics in Franceville. Blood samples were collected to test for HBV surface antigen, anti-hepatitis B core, hepatitis B e antigen, and anti-hepatitis B e markers and to assess HBV infection. Results: We recruited 901 women with a median age of 26 years (interquartile range: 21-32). Overall prevalence of infection was 3.9% (confidence interval: 2.7-5.4%). 418/901 or 46.4% were anti-hepatitis B core positive. Among HBV surface antigen-positive women, 1/35 were hepatitis B e antigen-positive with a viral load >200,000 IU/ml. Over 64% of participants had no information about HBV infection, and none knew that the virus could be transmitted from mother to child. Conclusions: This study reveals a low HBV prevalence in pregnant women in Gabon and a low risk of vertical transmission of the virus. However, the rate of exposure of the population to the virus remains high and calls for improving actions and interventions for potential elimination goals.

19.
IJID Reg ; 5: 121-123, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36217501

RESUMEN

Objectives: To estimate the seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibodies in the general population in the Republic of Congo. Methods: In this cross-sectional study, conducted from June to July 2021, participants were recruited from the general population in three districts in the Republic of Congo. Eligible participants were tested for anti-SARS-CoV-2 antibodies using a rapid diagnostic assay. Results: Overall, 31.8% [95% confidence interval (CI) 29.5-34.0] of the 1669 participants tested positive for anti-SARS-CoV-2 antibodies. Higher prevalence was observed in the rural region (37.3%, 95% CI 31.0-44.1%) than the urban region (30.9%, 95% CI 28.5-33.3); however, the difference was not significant. The risk of testing positive for anti-SARS-CoV-2 antibodies increased significantly with age, ranging from 22.5% (95% CI 18.1-27.5) in 15-24 year olds to 47.9% (95% CI 39.3-56.5) in 55-64 year olds. Conclusions: The antibody levels observed in this survey correlate with a moderate rate of virus circulation, which correlates with the low number of confirmed cases of coronavirus disease 2019 in the Republic of Congo.

20.
IJID Reg ; 5: 13-17, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36060857

RESUMEN

Objective: To estimate the seroprevalence of anti-SARS-CoV-2 antibodies in the general population in Gabon, Central Africa. Methods: From May to July 2021, a cross-sectional study involving participants recruited in the general population in three districts in Gabon was conducted. Eligible participants who provided written informed consent were tested for anti-SARS-CoV-2 antibodies using a simple rapid diagnostic assay. Results: Overall, 1609 participants were recruited, 1361 (84.6%) from urban sites and 248 (15.4%) from a rural area. The estimated overall seroprevalence was 13.1% (95% CI 11.4-14.8%). The risk of seropositivity increased with age, and the prevalence in the different age groups ranged from 12.9% (8.0-19.4%) in those aged 15-24 years to 23.3% (14.2-34.6%) in those ≥ 65 years old. A higher prevalence was found in the rural population (17.3%; 12.8-22.6%) compared with urban regions (12.3%; 10.6-14.1%). Being a woman was also associated with higher risk of infection (p < 0.001). Conclusions: This seroprevalence survey revealed a moderate seroprevalence in Gabon, illustrating a relatively low rate of circulation of the virus in the country and correlating with low numbers of confirmed cases and deaths reported to date.

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