Experts concerned about high prevalence of HIV-1 drug resistance

-among patients on first-line antiretroviral treatment
THE THREAT of HIV Drug Resistance in resource-poor countries is very real and frighteningly so, as gleaned from the findings of a study recently released in the Journal of the International AIDS Society of  June 10, 2011.
The study, conducted by Anoumou Dagnra et al of BioMed Central Ltd., Togo, has noted a high prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lomé, Togo and concludes:
“With widespread use of antiretroviral (ARV) drugs in Africa, one of the major potential challenges is the risk of emergence of ARV drug-resistant HIV strains.”
In their conclusion, the researchers note:  “In Togo, efforts to provide access to ARV therapy for infected persons have increased since 2003, and scaling up of ART started in 2007. The high number of resistant strains observed in Togo shows clearly that the emergence of HIV drug resistance is of increasing concern in countries where ART is now widely used, and can compromise the long-term success of first- and second-line ART.’
Such findings confirm the concerns expressed at the XVIII International HIV Drug Resistance Workshop held at the Sanibel Harbour Hotel, Fort Myers, Florida in June, 2008, about ‘HIV Drug-resistance in resource poor countries’.
Alluding to the fast-growing numbers of people now on antiretroviral therapy (ART) in low-and-middle-income countries increasing more that ten-fold in six years, and which by 2010 we saw, had exceeded 5 million, experts at the conference declared: 
“This enormous progress is potentially threatened by the selection and transmission of HIV drug resistance.” For this reason, the conference urged all scientists investigating HIV drug resistance internationally to share data and ideas, as well as develop potential synergistic collaborations.
Drug resistance is the ability of HIV to mutate and reproduce itself in the presence of anti-retroviral drugs whose function, in fact, is to suppress it.  The consequences of drug resistance include treatment failure; increased direct and indirect health costs associated with the need to start more costly second-line treatment for patients; the spread of resistant strains of HIV; and the need to develop new anti-HIV drugs.  The extent of HIV drug resistance resulting from ART scale up in data, diagnostic software, and information. (HIV ResNet).
Meanwhile, the study done in Lome, Togo, was to evaluate the virological failure and genotypic drug-resistance mutations in patients receiving first-line highly active antiretroviral therapy (HAART) in routine clinics that use the World Health Organization (WHO) public-health approach to monitor antiretroviral treatment (ART) in Togo.
The exercise measured plasma viral load of patients on HAART for one year (10-14 months), and was conducted at three sites in Lome, the capital of Togo and carried out  genotyopic drug-resistance testing with an in-house assay on plasma samples from patients with viral loads of more than 1000 copies/ml. CD4 cell counts and demographic data were also obtained from medical records.
Of a total of 188 patients receiving first-line antiretroviral treatment enrolled, 58 (30.8%) of them experienced virologic failure, and there was a high incidence of drug-resistance mutations in patients.
In Togo, efforts to provide access to ARV therapy for infected persons have increased since 2003, and scaling up of ART started in 2007. The high number of resistant strains observed in Togo shows clearly that the emergence of HIV drug resistance is of increasing concern in countries where ART is now widely used, and can compromise the long-term success of first- and second-line ART.
More from the JIAS Report: 
Background
Implementation of antiretroviral therapy (ART) is recognized as a public health priority in resource-limited countries. In order to allow a rapid roll out of ART, countries use the World Health Organization (WHO) public health approach, which proposes standard first-line therapy, together with treatment initiation and switch guided by clinical disease progression and, where possible, with monitoring of CD4 cell counts. The standard therapy consists of two nucleoside reverse transcriptase inhibitors (NRTIs) (3TC+AZT/d4T) and one non-nucleoside reverse transcriptase inhibitor (NRRTI) (EFV/NVP).
In 2010, these guidelines were revised and recommended less toxic drugs in first-line therapy by replacing stavudine (d4T) with tenofovir (TDF). Although a more strategic monitoring for ART efficacy is now also recommended, virological monitoring is still not feasible for the majority of patients on ART in sub-Saharan Africa due to the absence of adequate laboratory facilities and insufficient financial means.
In addition, deficiencies in health systems and resources, such as unreliable supply systems, storage and the lack of qualified personnel to prescribe and monitor patients on ART, could also create conditions for accelerated development of HIV resistance to antiretroviral (ARV) drugs. It is thus important to evaluate the outcome and effectiveness of ART programmes in routine care settings in resource-limited countries to evaluate whether the empirical second-line treatment recommended by WHO would still be effective.
Togo is a small country of 5.5 million inhabitants, located in west Africa, with an estimated HIV prevalence of around 3% in the general population. Scaling up of ART started in 2007, and approximately 7000 HIV-1-infected individuals were receiving ART by the end of 2007. Treatment became free of charge by the end of 2008 and, today, more than 17,000 people are receiving ART, which corresponds to coverage of 33%. Here we describe virological outcome and emergence of drug resistance in a cross-sectional study among HIV-1-infected patients treated according to the national guidelines in hospitals in Lomé, the capital city of Togo.
Methods
A total of 188 HIV-1-positive patients receiving first-line ART for 12 months (+/-2 months) were consecutively enrolled between April and October 2008 in three sites in Lomé: the University Hospital Tokoin; and two non-governmental organizations for HIV care, (EVT (Espoir Vie Togo) and CRIPS (Centre de Réflexion et d’Initiative pour la Promotion de la Santé). The study was approved by the National Ethics Commitee and Ministry of Health (N°0269/2007/MS/DGS/DPLET/CBRS). Only patients who declared that they were ARV treatment naïve prior to the start of first-line treatment and those without prior use of ARVs for prevention of mother to child transmission of HIV were included in this study. After written informed consent, whole blood was collected and plasma was separated from cells by centrifugation at 3000rpm for five minutes and stored at -80°C in three aliquots.
Results
During the study period, 580 HIV-1-infected patients attended one of the three clinics for their follow-up visit at M12, and a total of 188 were included in this study. The median duration of ARV therapy prior to study enrollment was 12 months, ranging from 10 to 14 months. The median age of patients was 37 years (IQR 32-43), and only 66 (35.1%) were male (Table 1). National guidelines for patient monitoring recommend monthly clinical visits and CD4 counts at start and every six months. CD4 counts were available for 160 patients at treatment initiation; a median CD4 cell count of 100 cells/mm3 (IQR 54-173) was seen, which increased to a median of 293 cells/mm3 (IQR 188-431) among the same 160 patients at the time of enrolment in this study, i.e., about 12 months later.

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