Thomas d. 'Aquin Toni

Bio: Thomas d. 'Aquin Toni is an academic researcher. The author has contributed to research in topics: Drug resistance & Viral load. The author has an hindex of 3, co-authored 3 publications receiving 136 citations.

Extraordinary Heterogeneity of Virological Outcomes in Patients Receiving Highly Antiretroviral Therapy and Monitored With the World Health Organization Public Health Approach in Sub-Saharan Africa and Southeast Asia

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.

Low prevalence of HIV type 1 drug resistance mutations in untreated, recently infected patients from Burkina Faso, Côte d'Ivoire, Senegal, Thailand, and Vietnam: the ANRS 12134 study.

Abstract: The frequency of transmitted HIV drug resistance (HIVDR) was evaluated in the context of rapid scale-up of antiretroviral treatment in Thailand, Vietnam, Burkina Faso, Cote d'Ivoire, and Senegal by using an adaptation of the WHO generic protocol of the HIV Drug Resistance Threshold Survey (HIVDR-TS) for sample collection and classification. Resistance-associated mutations were interpreted using the 2009 WHO list for epidemiological surveys. We included 266 subjects from the five study sites. Of the 266 RT and PR sequences analyzed, two from Vietnam harbored virus with major drug resistance mutations (G190A in RT for one individual and M46I in PR for the second individual). Phylogenetic analysis revealed that CRF01_AE predominates (>90%) in Thailand and Vietnam. CRF02 (>65%) cocirculates with other HIV-1 variants in Senegal and Cote d'Ivoire. The prevalence of HIVDRM is scored as low (≤5%) in all the five sites for the three drug classes analyzed. A continuous population survey for HIVDRM will pro...

Model-based cost-effectiveness estimates of testing strategies for diagnosing hepatitis C virus infection in Central and Western Africa

Abstract: Background Whereas 72% of hepatitis C virus (HCV)-infected people worldwide live in low- and middle-income countries (LMICs), only 6% of them have been diagnosed. Innovative technologies for HCV diagnosis provide opportunities for developing testing strategies more adapted to resource-constrained settings. However, studies about their economic feasibility in LMICs are lacking. Methods Adopting a health sector perspective in Cameroon, Cote-d'Ivoire, and Senegal, a decision tree model was developed to compare 12 testing strategies with the following characteristics: a one-step or two-step testing sequence, HCV-RNA or HCV core antigen as confirmative biomarker, laboratory or point-of-care (POC) tests, and venous blood samples or dried blood spots (DBS). Outcomes measures were the number of true positives (TPs), cost per screened individual, incremental cost-effectiveness ratios, and nationwide budget. Corresponding time horizon was immediate, and outcomes were accordingly not discounted. Detailed sensitivity analyses were conducted. Findings In the base-case, a two-step POC-based strategy including anti-HCV antibody (HCV-Ab) and HCV-RNA testing had the lowest cost, €8.18 per screened individual. Assuming a lost-to-follow-up rate after screening > 1.9%, a DBS-based laboratory HCV-RNA after HCV-Ab POC testing was the single un-dominated strategy, requiring an additional cost of €3653.56 per additional TP detected. Both strategies would require 8–25% of the annual public health expenditure of the study countries for diagnosing 30% of HCV-infected individuals. Assuming a seroprevalence > 46.9% or a cost of POC HCV-RNA < €7.32, a one-step strategy based on POC HCV-RNA dominated the two-step POC-based strategy but resulted in many more false-positive cases. Conclusions POC HCV-Ab followed by either POC- or DBS-based HCV-RNA testing would be the most cost-effective strategies in the study countries. Without a substantial increase in funding for health or a dramatic decrease in assay prices, HCV testing would constitute an economic barrier to the implementation of HCV elimination programs in LMICs.

HIV-1 drug resistance in antiretroviral-naive individuals in sub-Saharan Africa after rollout of antiretroviral therapy: a multicentre observational study

Abstract: Summary Background There are few data on the epidemiology of primary HIV-1 drug resistance after the roll-out of antiretroviral treatment (ART) in sub-Saharan Africa. We aimed to assess the prevalence of primary resistance in six African countries after ART roll-out and if wider use of ART in sub-Saharan Africa is associated with rising prevalence of drug resistance. Methods We did a cross-sectional study in antiretroviral-naive adults infected with HIV-1 who had not started first-line ART, recruited between 2007 and 2009 from 11 regions in Kenya, Nigeria, South Africa, Uganda, Zambia, and Zimbabwe. We did population-based sequencing of the pol gene on plasma specimens with greater than 1000 copies per mL of HIV RNA. We identified drug-resistance mutations with the WHO list for transmitted resistance. The prevalence of sequences containing at least one drug-resistance mutation was calculated accounting for the sampling weights of the sites. We assessed the risk factors of resistance with multilevel logistic regression with random coefficients. Findings 2436 (94.1%) of 2590 participants had a pretreatment genotypic resistance result. 1486 participants (57.4%) were women, 1575 (60.8%) had WHO clinical stage 3 or 4 disease, and the median CD4 count was 133 cells per μL (IQR 62–204). Overall sample-weighted drug-resistance prevalence was 5.6% (139 of 2436; 95% CI 4.6–6.7), ranging from 1.1% (two of 176; 0.0–2.7) in Pretoria, South Africa, to 12.3% (22 of 179; 7.5–17.1) in Kampala, Uganda. The pooled prevalence for all three Ugandan sites was 11.6% (66 of 570; 8.9–14.2), compared with 3.5% (73 of 1866; 2.5–4.5) for all other sites. Drug class-specific resistance prevalence was 2.5% (54 of 2436; 1.8–3.2) for nucleoside reverse-transcriptase inhibitors (NRTIs), 3.3% (83 of 2436; 2.5–4.2) for non-NRTIs (NNRTIs), 1.3% (31 of 2436; 0.8–1.8) for protease inhibitors, and 1.2% (25 of 2436; 0.7–1.7) for dual-class resistance to NRTIs and NNRTIs. The most common drug-resistance mutations were K103N (43 [1.8%] of 2436), thymidine analogue mutations (33 [1.6%] of 2436), M184V (25 [1.2%] of 2436), and Y181C/I (19 [0.7%] of 2436). The odds ratio for drug resistance associated with each additional year since the start of the ART roll-out in a region was 1.38 (95% CI 1.13–1.68; p=0.001). Interpretation The higher prevalence of primary drug resistance in Uganda than in other African countries is probably related to the earlier start of ART roll-out in Uganda. Resistance surveillance and prevention should be prioritised in settings where ART programmes are scaled up. Funding Ministry of Foreign Affairs of the Netherlands.

Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis

Abstract: 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.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-naive 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 positions—a proxy for recent infection—yielded trends comparable to those obtained using the complete dataset. Four NNRTI SDRMs—K101E, K103N, Y181C, and G190A—accounted 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.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.

Update on HIV-1 diversity in Africa: a decade in review.

Abstract: Background HIV-1 strains have diversified extensively through mutation and recombination since their initial transmission to human beings many decades ago in Central Africa in the first part of the 20th Century (between 1915 and 1941). The upward trend in global HIV-1 diversity has continued unabated, with newer groups, subtypes, and unique and circulating recombinants increasingly being reported, especially in Africa. Objective In this review, we focus on the extensive diversity of HIV-1 over a decade (2000-2011), in 51 countries of the three African geographic regions (eastern and southern, western and central, and northern Africa) as per the WHO/UNAIDS 2010 classification. Methodology References for this review were identified through searches of PubMed, conference abstracts, Google Scholar, and Springer Online Archives Collection. We retrieved 273 citations, of which 200 reported HIV-1 diversity from Africa from January, 2000 to August, 2011. Articles resulting from these searches and relevant references cited in those articles were reviewed. Articles published in English and French were included. Findings There has been a high diversity of HIV-1 in its epicenter, west-central Africa. A few subtypes, namely, A (A1, A2, A3, A4, A5), C, CRF02_AG, and D accounted for about 85% of new infections. Subtype A and D have been stable in East Africa; C in southern Africa; A, G, CRF02_AG, and CRF06_cpx in western Africa; and subtype B and CRF02_AG in northern Africa. Recently a new putative group, designated P, was reported to be found in two Cameroonians. Conclusion The regional distributions of individual subtypes and recombinants are broadly stable, although unique/circulating recombinant forms may play an increasing role in the HIV pandemic. Understanding the kinetics and directions of this continuing adaptation and its impact on viral fitness, immunogenicity, and pathogenicity are crucial to the successful design of effective HIV vaccines. There is need for regular monitoring and review updates, such as the one presented here, to assist countries to plan and anticipate complex forms that may be introduced with time.

Effect of mobile telephone reminders on treatment outcome in HIV: evidence from a randomised controlled trial in India.

Abstract: Objective To assess whether customised mobile phone reminders would improve adherence to therapy and thus decrease virological failure among HIV infected patients starting antiretroviral treatment (ART). Design Randomised controlled trial among HIV infected patients initiating antiretroviral treatment. Setting Three diverse healthcare delivery settings in south India: two ambulatory clinics within the Indian national programme and one private HIV healthcare clinic. Participants 631 HIV infected, ART naive, adult patients eligible to initiate first line ART were randomly assigned to mobile phone intervention (n=315) or standard care (n=316) and followed for 96 weeks.. Intervention The intervention consisted of customised, interactive, automated voice reminders, and a pictorial message that were sent weekly to the patients’ mobile phones for the duration of the study. Main outcome measures The primary outcome was time to virological failure (viral load >400 copies/mL on two consecutive measurements). Secondary outcomes included ART adherence measured by pill count, death rate, and attrition rate. Suboptimal adherence was defined as mean adherence <95%. Results Using an intention-to-treat approach we found no observed difference in time to virological failure between the allocation groups: failures in the intervention and standard care arms were 49/315 (15.6%) and 49/316 (15.5%) respectively (unadjusted hazard ratio 0.98, 95% confidence interval 0.67 to 1.47, P=0.95). The rate of virological failure in the intervention and standard care groups were 10.52 and 10.73 per 100 person years respectively. Comparison of suboptimal adherence was similar between both groups (unadjusted incidence rate ratio 1.24, 95% CI 0.93 to 1.65, P=0.14). Incidence proportion of patients with suboptimal adherence was 81/300 (27.0%) in the intervention arm and 65/299 (21.7%) in the standard care arm. The results of analyses adjusted for potential confounders were similar, indicating no significant difference between the allocation groups. Other secondary outcomes such as death and attrition rates, and subgroup analysis also showed comparable results across allocation groups. Conclusions In this multicentre randomised controlled trial among ART naive patients initiating first line ART within the Indian national programme, we found no significant effect of the mobile phone intervention on either time to virological failure or ART adherence at the end of two years of therapy. Trial registration Current Controlled Trials [ISRCTN79261738][1]. [1]: /external-ref?link_type=ISRCTN&access_num=ISRCTN79261738

Extraordinary Heterogeneity of Virological Outcomes in Patients Receiving Highly Antiretroviral Therapy and Monitored With the World Health Organization Public Health Approach in Sub-Saharan Africa and Southeast Asia

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.