Scale-up of antiretroviral treatment in sub-Saharan Africa is accompanied by increasing HIV-1 drug resistance mutations in drug-naive patients
Virology Laboratory CREMER/IMPM/IRD, Yaounde, Cameroon. AIDS (London, England)
(Impact Factor: 5.55).
08/2011; 25(17):2183-8. DOI: 10.1097/QAD.0b013e32834bbbe9
To evaluate the frequency and progression over time of the WHO-defined transmitted HIV-1 drug resistance mutations (DRMs) among antiretroviral treatment (ART)-naive HIV-1-infected patients in Cameroon.
We analyzed HIV-1 DRM data generated from 369 ART-naive individuals consecutively recruited between 1996 and 2007 in urban and rural areas in Cameroon.
HIV-1 drug resistance genotyping was performed in the pol gene using plasma samples and surveillance DRMs were identified using the 2009 WHO-DRM list.
We observed in Yaounde, the capital city, an increasing prevalence of DRMs over time: 0.0% (none of 61 participants) in 1996-1999; 1.9% (one of 53 participants) in 2001; 4.1% (two of 49 participants) in 2002; and 12.3% (10 of 81 participants) in 2007. In the rural areas with more recently implemented ART programs, we found DRMs in six of 125 (4.8%) ART-naive individuals recruited in 2006-2007. DRMs identified in both areas included resistance mutations to protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs (NNRTIs) that might impair the efficacy of available first-line and second-line treatments.
This report showed an increase in transmitted DRMs in areas where antiretroviral drugs were introduced earlier, although other factors such as natural viral polymorphisms and acquired DRMs through exposure to antiretroviral cannot be totally excluded. Further surveillances are needed to confirm this evolution and inform public health policies on adequate actions to help limit the selection and transmission of drug-resistant HIV, while scaling up access to ART in developing countries.
Available from: Marcel Joly
- "Data from the World Health Organization (WHO) show that there are more than 34 million people living with the human immunodeficiency virus (HIV) around the world (WHO, 2013). Whereas the scale-up of highly active antiretroviral therapy (HAART) has provided a dramatic reduction in morbidity and mortality in AIDS patients over the last decade, the population of HIV-infected individuals who have received multiple regimens or were infected with highly resistant viruses shows a continuous and perturbing increase worldwide (Aghokeng et al., 2011; Shafer et al., 2007). Included here are pediatric patients, who require treatment during critical phases of growth and development, as well as the lifelong need for therapy (Königs et al., 2012). "
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ABSTRACT: The dramatic reduction in morbidity and mortality associated with the use of highly active antiretroviral therapy has created new challenges for clinicians: AIDS has become a chronic, potentially life-threatening, condition in many clinical instances. In this paper, a novel system engineering approach based on mixed-integer linear programming (MILP) is presented to support HIV/AIDS clinicians when formulating real-world therapeutic plans for heavily treatment-experienced patients under variable settings. Our results suggest that, while current practices (standard protocols and/or subjective recommendations based on the clinician's experience) can generally provide satisfactory management of drug resistance in the short-term, optimization-based therapy planning has a far greater potential to achieve this goal over expanded time horizons thereby changing paradigms and rethinking best practices in the HIV/AIDS clinical arena. Moreover, the ability of this methodology to address other viral pathologies (e.g., hepatitis B and C virus) can make this work appeal to a broader audience.
Available from: Knut Holtedahl
- "This is in spite of the limited local therapeutic offer of one standard ART combination and one available second line alternative. In Cameroon, scale-up of ART has been shown to be associated with increased drug resistance mutations
, and resistance monitoring may be the next priority after CD4 access
. Routine measuring of viral load seems to be a lesser priority
[17, 18]. "
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ABSTRACT: BackgroundOptimal starting point for antiretroviral treatment (ART) has been uncertain.MethodsParallel group, single blind, randomised controlled study of adult HIV positive patients consulting at the Protestant Hospital, Ngaoundere, Cameroon in 2007-8. Simple randomisation of patients in WHO clinical stage 1-2 to start of ART early or deferred, i.e. when CD4 counts dropped below 350 versus 250 cells/mm3, or when they reached clinical stage 3-4. Clinical follow-up every three months were offered for all patients. Main outcomes were clinical stage, CD4 differences and mortality. Of 424 consulting patients, most were excluded, mainly because they were already in WHO stage 3-4. Forty-four patients were randomised.ResultsIn the ‘early’ group two patients died and five were lost to follow-up. In the ‘deferred’ group, six patients died and nine were lost to follow-up (Hazard ratio for death by early compared to deferred treatment 0.26, 95% confidence interval 0.05-1.29). Of the patients lost to follow-up, three patients in the ‘early’ group and four patients in the ‘deferred’ group were known to be alive when the study ended. Fourteen patients in the early group and 11 in the deferred group started ART. Twenty-two patients were evaluated clinically six to seven months after the study period was terminated. Except for one patient with AIDS, these were all still in clinical stage 1-2.ConclusionsIn our small sample, relative risk for death did not differ significantly, but deferred treatment seemed to carry no increased survival or other clinical advantage. During the study period, other studies made WHO change its guidelines to conform to our early treatment. The tendency in our study lends support to this policy.Trial registrationISRCTN22114173Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2458-14-828) contains supplementary material, which is available to authorized users.
Available from: Joseph Fokam
- "More importantly, recent studies in Cameroon showed low to moderate levels of transmitted HIVDR , and increasing levels of acquired HIVDR after 12 and 24 months , thus predicting growing risks of treatment failure and HIVDR to the commonly used drugs, due to a broad range of factors [35,39]. Without attempting to create a direct temporal relationship, the increasing rate of transmitted and acquired HIVDR in Cameroon, alongside the increasing/widely availability of ARV treatment, supports also a growing need of affordable viral load and HIVDR testing, and a more regular surveillance of HIVDR in this country [8,38]. Pediatric HIVDR surveillance is of prime importance, and needs to be implemented . "
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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.
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.
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, EWI3, 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.
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.
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