Drug resistance during follow up of a case with HIV infection
Abstract
Dear Editor Human immunodeficiency virus HIV continues to cause a high rate of morbidity and mortality despite drug and vaccine studies conducted with a high speed worldwide According to the data of the World Health Organization the number of HIV positive pregnant women who receive antiretroviral treatment increase each day in countries with low moderate income level Infection is acquired during pregnancy during delivery or in the breastfeeding period in more than 90 of the children infected with human immunodeficiency virus 1 Therefore prevention of transmission from infected women to their infants in addition to prevention of infection in women who are in the child bearing period is important 2 Treatment may be required in case of transmission from the mother to the infant which occurs in spite all precautions In follow up of infection acquired at youger ages noncomplicance with treatment or drug resistance frequently leads to problems With this case we would like to draw attention to development of drug resistance and its management in cases who are followed up because of HIV infection and in whom drug resistance develops HIV was found to be positive in a subject in screening performed at the age of 11 because of presence of HIV infection in the mother After this date lamivudine nevirapine and zidovudine combination treatment was started The patient used this treatment for two years irregularly and was lost to follow up for a period of one year Afterwards viral load was found to be increased as 6 67 E2 copies ml at presentation Transaminase levels and renal function were found to be normal total white blood cell count was found to be 3510 mm3 and the rate of CD 4 T cells was observed to be decreased to 29 534 mm3 There was no special finding in the personal medical history except for hospitalization because of lung infection 2 years ago In the familial history it was learned that HIV infection was found in the father during investigations performed bacause of intracranial abcess and the father died because of this It was also learned that HIV infection was also found in the mother simultaneously On physical examination growth and development were found to be normal and no extraordinary finding was observed No diagnostic test for HIV infection had been performed before but transmission from the mother was considered since the mother had HIV infection Since irregular drug use was reported it was anticipated that drug resistance might have been developed Drug resistance test was done in Refik Saydam Hıfzısıhha Institute Lamuvidine was shown to have methionine valine transition M184V high resistance mutations against nucleoside reverse transcriptase inhibitors NRTI and valine alanine transition V106A resistance mutations against non nucleoside reverse transcriptase inhibitors NNRTI Considering antiretroviral treatment protocol used for children treatment was arranged as 2 NRTI Zidovudine Tenofovir and one protease inhibitor Lopinavir Ritonavir selected according to resistance results in subjects who previously received 2 NRTIs and 1 NNRTI treatment if resistance developed 3 No problem has been observed in the one year follow up of the subject whose viral load decreased at the end of a follow up period of one month viral load test was found to be negative at the second month and CD4 positive lymphocyte level was normal Resistance develops during treatment of human immunodeficiency virus because of incomplete compliance with treatment and this affects the survival negatively if early intervention is not performed Introduction of the approach of use of NRTIs initially and combined antiretroviral treatment cART afterwards has substantially decreased the mortality and morbidity related to HIV 4 Although successful results are obtained with treatment regimes containing lamivudine 3TC mutations at a single position including M184V cause a decrease in drug sensitivity by 100 1000 fold 5 Methionine valine transition mutation is mainly responsible of development of resistance against lamivudine with a high rate but is also responsible of resistance against other drugs in this group 6 7 Valine alanine transition mutation is associated with resistance against non nucleoside reverse transcriptase inhibitors and especially with resistance against nevirapine 8 Since development of new resistance against the drugs used during treatment is possible subjects who receive HIV treatment should be followed up closely If any minor suspicion of resistance is present resistance tests should be performed and a new treatment regime should be started without losing time evaluating treatment options in line with the results of these tests Address for Correspondence: Başak Yıldız MD Ege University Medical Faculty Division of Pediatric Infectious Diseases İzmir Turkey E mail: basakyildiz@gmail com Received: 12 23 2011 Accepted: 01 02 2011 References 1 World Health Organization HIV AIDS Department Towards universal access: Scaling up priority HIV AIDS interventions in the health sector Progress report 2010: 90 2 World Health Organization HIV AIDS Department Strategic approaches to the prevention of HIV infection in infants: report of a WHO meeting Morges Switzerland: Geneva 2002 3 Working Group on Antiretroviral Therapy and Medical Management of HIV Infected Children Guidelines for the use of antiretroviral agents in pediatric HIV infection 2009; 91 2 4 Pallela FJ Delaney KM Moorman AC et al Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection N Engl J Med 1998;338: 853 60 [Abstract] 5 Brenner BG Turner D Wainberg MA HIV 1 drug resistance: can we overcome? Expert Opin Biol Ther 2002;2: 751 61 [Abstract] nbsp; 6 Ait Khaled M Stone C Amphlett G et al M184V is associated with a low incidence of thymidine analogue mutations and low phenotypic resistance to zidovudine and stavudine AIDS 2002;16 12 : 1686 9 [Abstract] nbsp; 7 Lafeuillade A Poggi C Hittinger G et al Phenotypic and genotypic resistance to nucleoside reverse transcriptase inhibitors in HIV 1 clinical isolates HIV Med 2001;2 4 : 231 5 nbsp; [Abstract] nbsp; 8 Millinkoviç A Martinez E Nevirapine in the treatment of HIV Expert Rev Anti Infect Ther 2004;2 3 : 367 73
Keywords
HİV enfeksiyonu nedeniyle izlenen bir olguda gelişen ilaç direnci
Öz
İnsan immün yetersizlik virüsü (HİV), tüm dünyada hızla sürdürülen ilaç ve aşı çalışmalarına rağmen halen yüksek oranda ölüm ve hastalığa neden olmaya devam etmektedir. Dünya Sağlık Örgütü’nün verilerine göre düşük-orta düzeyde gelir seviyesine sahip ülkelerde antiretroviral tedavi almakta olan HİV pozitif gebe kadın sayısı her gün daha da artmaktadır. İnsan immün yetersizlik virüsü ile enfekte çocukların %90’ından fazlasında enfeksiyon gebelik süresince, doğum sırasında veya emzirme döneminde kazanılmıştır (1). Doğurgan çağdaki kadınların enfeksiyondan korunmasının yanı sıra enfekte kadınlardan bebeklerine bulaşın önlenmesi bu nedenle önem taşımaktadır (2). Tüm çabalara rağmen anneden bebeğe geçiş durumunda tedavi gerekliliği doğabilmektedir. Küçük yaşta kazanılan enfeksiyonun izleminde tedaviye uyumsuzluk veya ilaç direnci gibi durumlar sıklıkla sorun yaratabilmektedir. Bu olgu aracılığı ile HİV enfeksiyonu nedeni ile izlenen ve tedavi sürecinde ilaç direnci gelişen olgularda ilaç direnci gelişimi ve tedavisine dikkat çekmek istiyoruz.
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