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Fokam J.,Chantal International Reference Center for Research on AIDS Prevention and Management | Fokam J.,University of Yaounde I | Billong S.C.,University of Yaounde I | Billong S.C.,Central Technical Group CTG | And 15 more authors.
BMC Public Health | Year: 2013

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: EWI1 (100% to 70%); EWI2 (40% to 20%); EWI3 (70% to 0%); EWI4 (0% throughout); EWI5 (90% to 40%). Thus, prescribing practices (EWI1) were in conformity with national guidelines, while patient adherence (EWI2, EWI 3, and EWI4) and drug supply (EWI5) 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. © 2013 Fokam et al.; licensee BioMed Central Ltd.


Rhee S.-Y.,Stanford University | Jordan M.R.,Tufts University | Raizes E.,Centers for Disease Control and Prevention | Chua A.,Médecins Sans Frontières | And 32 more authors.
PLoS ONE | Year: 2015

The increasing prevalence of acquired and transmitted HIV-1 drug resistance is an obstacle to successful antiretroviral therapy (ART) in the low- and middle-income countries (LMICs) hardest hit by the HIV-1 pandemic. Genotypic drug resistance testing could facilitate the choice of initial ART in areas with rising transmitted drug resistance (TDR) and enable care-providers to determine which individuals with virological failure (VF) on a first- or second-line ART regimen require a change in treatment. An inexpensive near point-of-care (POC) genotypic resistance test would be useful in settings where the resources, capacity, and infrastructure to perform standard genotypic drug resistance testing are limited. Such a test would be particularly useful in conjunction with the POC HIV-1 viral load tests that are currently being introduced in LMICs. A POC genotypic resistance test is likely to involve the use of allele-specific point mutation assays for detecting drug-resistance mutations (DRMs). This study proposes that two major nucleoside reverse transcriptase inhibitor (NRTI)-associated DRMs (M184V and K65R) and four major NNRTI-associated DRMs (K103N, Y181C, G190A, and V106M) would be the most useful for POC genotypic resistance testing in LMIC settings. One or more of these six DRMs was present in 61.2% of analyzed virus sequences from ART-naïve individuals with intermediate or high-level TDR and 98.8% of analyzed virus sequences from individuals on a first-line NRTI/NNRTI-containing regimen with intermediate or high-level acquired drug resistance. The detection of one or more of these DRMs in an ART-naïve individual or in a individual with VF on a first-line NRTI/NNRTI-containing regimen may be considered an indication for a protease inhibitor (PI)-containing regimen or closer virological monitoring based on cost-effectiveness or country policy.


Nlend A.E.N.,National Insurance Fund Welfare Hospital | Nlend A.E.N.,University of Yaounde I | Nguwoh P.S.,Higher Institute of Health Professions | Nguwoh P.S.,Ministry of Public Health | And 16 more authors.
PLoS ONE | Year: 2016

Background: Since 2005, anti-hepatitis B virus (anti-HBV) vaccine is part of the Expanded Program on Immunization (EPI) for infants born in Cameroon, with 99% anti-HBV coverage. In a context of generalized HIV epidemiology, we assessed paediatric anti-HBV vaccine response according to HIV status, feeding option and age in a tropical context. Methodology: Prospective, observational and cross-sectional study conducted among 82 children (27 [IQR: 9-47] months, min-max: 6-59), after complete anti-HBV vaccination (Zilbrix Hepta: 10μg AgHBs) at the Essos Health Centre in Yaounde, Cameroon, classified as group-A: HIV unexposed (28), group-B: HIV-exposed/uninfected (29), group-C: HIV-infected (25). Quantitative anti-HBs ELISA was interpreted as "no", "low-" or "protective-response" with <1,1-10, or ≥10 IU/L respectively; with p-value<0.05 considered significant. Results: Children were all HBV-unexposed (AcHBc-negative) and uninfected (HBsAg-negative). Response to anti-HBV vaccine was 80.49% (66/82), with only 45.12% (37/82) developed a protective-response (≥10IU/L). According to HIV status, 60.71% (17/28) developed a protective-response in group-A, vs. 51.72% (15/29) and 20% (5/25) in group-B and group-C respectively, Odds Ratio (OR):2.627 [CI95% 0.933-7.500], p = 0.041. According to feeding option during first six months of life, 47.67% (21/45) developed a protective-response on exclusive breastfeeding vs. 43.24% (16/37) on mixed or formula feeding, OR: 1.148 [CI95% 0.437-3.026], p = 0.757. According to age, protective-response decreased significantly as children grow older: 58.33% (28/48) <24 months vs. 26.47% (9/34) ≥24 months, OR: 3.889 [CI95%1.362-11.356], p = 0.004; and specifically 67.65% (23/34) ≤6 months vs. 0%, (0/5) 33-41 months, p = 0.008. Conclusions: Anti-HBV vaccine provides low rate of protection (<50%) among children in general, and particularly if HIV-exposed, infected and/or older children. Implementing policies for early vaccination, specific immunization algorithm for HIV-exposed/infected children, and monitoring vaccine response would ensure effective protection in tropical settings, pending extensive/confirmatory investigations. © 2016 Njom Nlend et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Fokam J.,Chantal International Reference Center for Research on AIDS Prevention and Management | Fokam J.,University of Yaounde I | Fokam J.,University of Rome Tor Vergata | Fokam J.,National HIV Drug Resistance Surveillance and Prevention Working Group | And 22 more authors.
PLoS ONE | Year: 2015

Background: The majority (>95%) of new HIV infection occurs in resource-limited settings, and Cameroon is still experiencing a generalized epidemic with ~122,638 patients receiving antiretroviral therapy (ART). A detrimental outcome in scaling-up ART is the emergence HIV drug resistance (HIVDR), suggesting the need for pragmatic approaches in sustaining a successful ART performance. Methods: A survey was conducted in 15 ART sites of the Centre and Littoral regions of Cameroon in 2013 (10 urban versus 05 rural settings; 8 at tertiary/secondary versus 7 at primary healthcare levels), evaluating HIVDR-early warning indicators (EWIs) as-per the 2012 revised World Health Organization's guidelines: EWI1 (on-time pill pick-up), EWI2 (retention in care), EWI3 (no pharmacy stock-outs), EWI4 (dispensing practices), EWI5 (virological suppression). Poor performance was interpreted as potential HIVDR. Results: Only 33.3%(4/12) of sites reached the desirable performance for "on-time pill pick-up" (57.1% urban versus 0% rural; p < 0.0001) besides 25% (3/12) with fair performance. 69.2% (9/13) reached the desirable performance for "retention in care" (77.8% urban versus 50% rural; p=0.01) beside 7.7% (1/13) with fair performance. Only 14.4%(2/13) reached the desirable performance of "no pharmacy stock-outs" (11.1% urban versus 25% rural; p=0.02). All 15 sites reached the desirable performance of 0% "dispensing mono- or dual-therapy". Data were unavailable to evaluate "virological suppression" due to limited access to viral load testing (min-max: < 1%-15%). Potential HIVDR was higher in rural (57.9%) compared to urban (27.8%) settings, p=0.02; and at primary (57.9%) compared to secondary/tertiary (33.3%) healthcare levels, p=0.09. Conclusions: Delayed pill pick-up and pharmacy stock-outs are major factors favoring HIVDR emergence, with higher risks in rural settings and at primary healthcare. Retention in care appears acceptable in general while ART dispensing practices are standard. There is need to support patient-adherence to pharmacy appointments while reinforcing the national drug supply system. Copyright: © 2015 Fokam et al.


Tang M.W.,Stanford University | Rhee S.-Y.,Stanford University | Bertagnolio S.,WHO HTM TCO | Ford N.,WHO HTM TCO | And 54 more authors.
Journal of Infectious Diseases | Year: 2013

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.MethodsWe 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.ResultsMutations 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.ConclusionsRegardless of concomitant nevirapine vs. efavirenz, therapy duration, or subtype, tenofovir was more likely than zidovudine to retain antiviral activity following first-line d4T therapy. © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.


PubMed | University of Witwatersrand, Brown University, Médecins Sans Frontières, Ministry of Health and 21 more.
Type: Journal Article | Journal: PloS one | Year: 2015

The increasing prevalence of acquired and transmitted HIV-1 drug resistance is an obstacle to successful antiretroviral therapy (ART) in the low- and middle-income countries (LMICs) hardest hit by the HIV-1 pandemic. Genotypic drug resistance testing could facilitate the choice of initial ART in areas with rising transmitted drug resistance (TDR) and enable care-providers to determine which individuals with virological failure (VF) on a first- or second-line ART regimen require a change in treatment. An inexpensive near point-of-care (POC) genotypic resistance test would be useful in settings where the resources, capacity, and infrastructure to perform standard genotypic drug resistance testing are limited. Such a test would be particularly useful in conjunction with the POC HIV-1 viral load tests that are currently being introduced in LMICs. A POC genotypic resistance test is likely to involve the use of allele-specific point mutation assays for detecting drug-resistance mutations (DRMs). This study proposes that two major nucleoside reverse transcriptase inhibitor (NRTI)-associated DRMs (M184V and K65R) and four major NNRTI-associated DRMs (K103N, Y181C, G190A, and V106M) would be the most useful for POC genotypic resistance testing in LMIC settings. One or more of these six DRMs was present in 61.2% of analyzed virus sequences from ART-nave individuals with intermediate or high-level TDR and 98.8% of analyzed virus sequences from individuals on a first-line NRTI/NNRTI-containing regimen with intermediate or high-level acquired drug resistance. The detection of one or more of these DRMs in an ART-nave individual or in a individual with VF on a first-line NRTI/NNRTI-containing regimen may be considered an indication for a protease inhibitor (PI)-containing regimen or closer virological monitoring based on cost-effectiveness or country policy.


PubMed | University of Yaounde I, Higher Institute of Health Professions, Institute of Science and Technology Applied to Health, Chantal International Reference Center for Research on AIDS prevention and management and 2 more.
Type: Journal Article | Journal: PloS one | Year: 2016

Since 2005, anti-hepatitis B virus (anti-HBV) vaccine is part of the Expanded Program on Immunization (EPI) for infants born in Cameroon, with 99% anti-HBV coverage. In a context of generalized HIV epidemiology, we assessed paediatric anti-HBV vaccine response according to HIV status, feeding option and age in a tropical context.Prospective, observational and cross-sectional study conducted among 82 children (27 [IQR: 9-47] months, min-max: 6-59), after complete anti-HBV vaccination (Zilbrix Hepta: 10g AgHBs) at the Essos Health Centre in Yaounde, Cameroon, classified as group-A: HIV unexposed (28), group-B: HIV-exposed/uninfected (29), group-C: HIV-infected (25). Quantitative anti-HBs ELISA was interpreted as no, low- or protective-response with <1, 1-10, or 10 IU/L respectively; with p-value<0.05 considered significant.Children were all HBV-unexposed (AcHBc-negative) and uninfected (HBsAg-negative). Response to anti-HBV vaccine was 80.49% (66/82), with only 45.12% (37/82) developed a protective-response (10IU/L). According to HIV status, 60.71% (17/28) developed a protective-response in group-A, vs. 51.72% (15/29) and 20% (5/25) in group-B and group-C respectively, Odds Ratio (OR): 2.627 [CI95% 0.933-7.500], p = 0.041. According to feeding option during first six months of life, 47.67% (21/45) developed a protective-response on exclusive breastfeeding vs. 43.24% (16/37) on mixed or formula feeding, OR: 1.148 [CI95% 0.437-3.026], p = 0.757. According to age, protective-response decreased significantly as children grow older: 58.33% (28/48) <24 months vs. 26.47% (9/34) 24 months, OR: 3.889 [CI95% 1.362-11.356], p = 0.004; and specifically 67.65% (23/34) 6 months vs. 0%, (0/5) 33-41 months, p = 0.008.Anti-HBV vaccine provides low rate of protection (<50%) among children in general, and particularly if HIV-exposed, infected and/or older children. Implementing policies for early vaccination, specific immunization algorithm for HIV-exposed/infected children, and monitoring vaccine response would ensure effective protection in tropical settings, pending extensive/confirmatory investigations.


Fokam J.,Chantal International Reference Center for Research on AIDS Prevention and Management | Fokam J.,University of Yaounde I | Salpini R.,University of Rome Tor Vergata | Santoro M.M.,University of Rome Tor Vergata | And 12 more authors.
Pediatric Infectious Disease Journal | Year: 2011

Background: Scale-up to antiretroviral therapy (ART) requires surveillance for HIV drug resistance. With the goal of attaining 100% pediatric ART coverage in Cameroon, strategies to limit the spread of HIV resistance among children are very important. Methods: From June 2009 through February 2011, 92 HIV-1-infected children (41 ART-naive, 51 failing first-line ART) living in Yaoundé, Cameroon, were enrolled; HIV-1 Prot-RT genotypic resistance testing (GRT) was performed using an inhouse assay. Among 40 children failing first-line ART, treatment response was evaluated at weeks 24 and 48 after treatment was changed, based on GRT results. Results: The mean age was 72 months both for children who were drug-naive and those failing ART (range: 3-144 and 12-144, respectively), with a mean viremia of 5.59 log and 4.71 log RNA copies/mL, a median CD4 of 17% (588 cells/μL) and 23% (719 cells/μL), respectively. Median time-to-treatment failure was 610 days. A prevalence of 4.9% and 90% drug resistance was observed, respectively, among children who were drug-naive and those failing first-line ART, with circulating recombinant form CRF02-AG as the most prevalent clade (58.6% and 62%, respectively). After a change to GRT-based treatment, more than 90% of children had viremia <3 log RNA copies/mL at week 24 and confirmed at week 48, with 70% achieving undetectable viremia, although without correlation to immune response; 97.5% had switched to lopinavir/ritonavir-containing regimens. Conclusion: HIV-1 drug resistance was low among ART-naive children and very high among those failing first-line ART. Treatment change based on GRT was successful for most children, with lopinavir/ritonavir regimens being very promising for second-line use. © 2011 by Lippincott Williams & Wilkins.


PubMed | Chantal International Reference Center for Research on AIDS Prevention and Management
Type: Journal Article | Journal: The Pediatric infectious disease journal | Year: 2011

Scale-up to antiretroviral therapy (ART) requires surveillance for HIV drug resistance. With the goal of attaining 100% pediatric ART coverage in Cameroon, strategies to limit the spread of HIV resistance among children are very important.From June 2009 through February 2011, 92 HIV-1-infected children (41 ART-naive, 51 failing first-line ART) living in Yaound, Cameroon, were enrolled; HIV-1 Prot-RT genotypic resistance testing (GRT) was performed using an inhouse assay. Among 40 children failing first-line ART, treatment response was evaluated at weeks 24 and 48 after treatment was changed, based on GRT results.The mean age was 72 months both for children who were drug-naive and those failing ART (range: 3-144 and 12-144, respectively), with a mean viremia of 5.59 log and 4.71 log RNA copies/mL, a median CD4 of 17% (588 cells/L) and 23% (719 cells/L), respectively. Median time-to-treatment failure was 610 days. A prevalence of 4.9% and 90% drug resistance was observed, respectively, among children who were drug-naive and those failing first-line ART, with circulating recombinant form CRF02_AG as the most prevalent clade (58.6% and 62%, respectively). After a change to GRT-based treatment, more than 90% of children had viremia <3 log RNA copies/mL at week 24 and confirmed at week 48, with 70% achieving undetectable viremia, although without correlation to immune response; 97.5% had switched to lopinavir/ritonavir-containing regimens.HIV-1 drug resistance was low among ART-naive children and very high among those failing first-line ART. Treatment change based on GRT was successful for most children, with lopinavir/ritonavir regimens being very promising for second-line use.

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