Widespread resistance to antiretrovirals among children in the Central African Republic

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HIV-positive children who are being treated with antiretroviral drugs in the Central African Republic are infected with a wide variety of HIV subtypes, don’t adhere well to their treatment, and seldom have an undetectable viral load, according to a study published in the December 15th edition of the Journal of Acquired Immune Deficiency Syndromes. The investigators also found that resistance to antiretroviral drugs was widespread.

Some 90% of the world’s 2 million HIV-positive children live in sub-Saharan Africa. Access to antiretroviral therapy in this region is increasing. For reasons of cost and ease of adherence a commonly prescribed regimen is d4T/3TC/nevirapine in a coformulated pill. There is good evidence that children in sub-Saharan Africa can achieve good outcomes when they receive treatment with anti-HIV drugs, but there are limited data on the profile of HIV drug resistance amongst children in this region.

Investigators from the Central African Republic and France therefore designed a study involving 52 children receiving HIV treatment whose median age was eight years. The researchers determined the HIV subtype with which these children were infected. Adherence to treatment was assessed using a questionnaire, and changes in CD4 cell percentage and count as well as viral load were measured six months after the initiation of antiretroviral therapy. Data were also gathered on the presence of drug resistance.

Glossary

subtype

In HIV, different strains which can be grouped according to their genes. HIV-1 is classified into three ‘groups,’ M, N, and O. Most HIV-1 is in group M which is further divided into subtypes, A, B, C and D etc. Subtype B is most common in Europe and North America, whilst A, C and D are most important worldwide.

CD4 cell percentage

The CD4 cell percentage measures the proportion of all white blood cells that are CD4 cells.

drug resistance

A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus.

plasma

The fluid portion of the blood.

paediatric

Of or relating to children.

The most commonly used antiretroviral regimen was d4T/3TC/nevirapine with 46% of children receiving this in a coformulation and a further 19% as separate pills. Adherence was rated as “poor”(below 60%) in 57% of children, with only 14% having “very good” adherence (above 90%).

HIV subtype was measured in 26 children. The most commonly found were CRF11_cpx (38%), AE (15%), and AG (12%).

Before HIV treatment was started, median CD4 cell percentage was very low, being just 6%, median CD4 cell count at this time being 128 cells/mm3. After six months of treatment, median CD4 cell percentage had increased to 15%, with median CD4 cell count being 420 cells/mm3.

After six months of treatment, only 25% of children had a viral load below 50 copies/ml, all these children having adherence above 90%. Median viral load in the remaining children was approximately 2000 copies/ml.

A total of 26 children had resistance tests. Only 23% had HIV that was fully sensitive to anti-HIV drugs, the remaining 77% having HIV that was resistant to at least one anti-HIV drug.

The most common resistance mutation was M184V, found in 18 children (69%) and conferring resistance to 3TC. Resistance to d4T (and AZT) was detected in four children (15%). NNRTI resistance was present in 14 (54%) individuals.

Overall, five (19%) had resistance to one drug in their treatment, 4 (54%) to two drugs and one (4%) to all three drugs.

“Despite a significant increase in CD4 T-cell count from baseline, HIV viral load remained detectable in 75% of antiretroviral-treated children and middle or poor adherence was observed in 69%”, comment the investigators. This poor adherence meant that “viruses resistant to at least one antiretroviral drug were found in 77% of the children with virological failure.”

They also note that the HIV subtypes present in the children in this study were somewhat more diverse than those seen in earlier research.

“These findings highlight the interest of improving adherence and carrying out HIV plasma viral load determination for antiretroviral therapies monitoring of paediatric AIDS in Africa because of their high sensitivity to early diagnose treatment failure”, conclude the investigators.

References

Gody J-C et al. High prevalence of antiretroviral drug resistance mutations and HIV-1 non-B subtype strains from children receiving antiretroviral therapy regimen according to the 2006 revised WHO recommendations. J Acquir Immune Defic Syndr 49: 566-69, 2008.