Maternal 12-month response to antiretroviral therapy following prevention of mother-to-child transmission of HIV type 1, Ivory Coast, 2003-2006.

OBJECTIVE: Our aim was to study the response to antiretroviral treatment among women exposed to single-dose nevirapine (NVP) and/or short-course zidovudine (ZDV; with or without lamivudine [3TC]) for the prevention of mother-to-child transmission of human immunodeficiency virus (HIV) infection. METHODS: All HIV type 1-infected women who initiated antiretroviral treatment with stavudine or ZDV, 3TC, and NVP or efavirenz were eligible for the MTCT-Plus program in Abidjan, Ivory Coast. Exposed women had received either single-dose NVP alone or short-course ZDV (with or without 3TC) plus single-dose NVP during previous pregnancy. Genotypic resistance testing was performed at week 4 after delivery. Virologic failure was defined as a plasma HIV RNA level >500 copies/mL 12 months after initiation of antiretroviral treatment. RESULTS: Among 247 women who received antiretroviral treatment, 109 (44%) were unexposed; 81 had received short-course ZDV with 3TC, as well as single-dose NVP; 5 had received short-course ZDV plus 3TC; 50 had received short-course ZDV plus single-dose NVP; and 2 had received single-dose NVP alone. No ZDV mutation was detected in the 115 women whose specimens were available for genotypic testing; 11 (15.1%) of 73 women with 3TC exposure who were tested after delivery had 3TC resistance mutations. Three (4.3%) of 69 women exposed to short-course ZDV and 3TC plus single-dose NVP and 16 (38.1%) of 42 women exposed to short-course ZDV plus single-dose NVP had NVP resistance mutations. Antiretroviral treatment was initiated a median of 21 months after the intervention to prevent mother-to-child HIV transmission (median CD4(+) T lymphocyte count, 188 cells/mm(3)). Month 12 virologic failure was identified in 42 (19.2%) of 219 women for whom data were available, and multivariate analysis revealed that it was associated with poor adherence to treatment (adjusted odds ratio [aOR], 12.7; 95% confidence interval [CI], 3.0-53.9), postpartum 3TC resistance mutations (aOR, 6.9; 95% CI, 1.1-42.9), and a baseline CD4(+) T lymphocyte count <200 cells/mm(3) (aOR, 0.3; 95% CI, 0.2-0.8). NVP resistance was not associated with virological failure (aOR, 1.8; 95% CI, 0.5-6.5). CONCLUSIONS: Our study found that poor adherence and 3TC resistance acquired after the intervention to prevent mother-to-child transmission of HIV infection were associated with virologic failure in women who initiated antiretroviral treatment.     

Absence of zidovudine resistance in antiretroviral-naive patients following zidovudine/lamivudine/protease inhibitor combination therapy: virological evaluation of the AVANTI 2 and AVANTI 3 studies

OBJECTIVES: To assess the role of resistance mutations in subjects experiencing virological failure on zidovudine (ZDV) and lamivudine (3TC) combined with a protease inhibitor (PI) to those failing on ZDV/3TC alone. DESIGN AND METHODS: Samples were obtained from previously antiretroviral therapy-naive subjects enrolled into two studies, AVANTI 2 and AVANTI 3. Subjects were randomized to receive either: ZDV/3TC or ZDV/3TC plus indinavir (IDV) for 52 weeks (AVANTI 2), and ZDV/3TC or ZDV/3TC and nelfinavir (NFV) for 28 weeks (AVANTI 3). Emergence of viral resistance mutations was monitored by population sequencing and phenotypic resistance was determined by the recombinant virus assay. RESULTS: Genotypic data were obtained for subjects with plasma HIV-1 RNA > 400 copies/ml. In AVANTI 2, ZDV mutations were detected in 27% of ZDV/3TC-treated patients at week 52, but were absent in subjects treated with ZDV/3TC/IDV. No subjects from either arm of AVANTI 3 developed ZDV resistance mutations at week 28. The M184V mutation developed in most ZDV/3TC-treated subjects from both studies. The presence of M184V was, however, associated with significantly lower plasma viral RNA levels when compared with values obtained before initiation of treatment. There was a high frequency (4 of 11) of the protease L10F substitution in ZDV/3TC/IDV-treated patients that was associated with virological failure but did not result in phenotypic resistance to any of the PIs tested. CONCLUSIONS: ZDV mutations were not detected in ZDV/3TC/PI-treated patients and they developed slowly in those treated with ZDV/3TC. Few protease mutations known to confer phenotypic PI resistance developed in the ZDV/3TC/PI arms of either study. The low prevalence of ZDV and PI mutations is encouraging regarding the future treatment options of these patients.     

The association between primary antiretroviral resistance and HAART virologic failure in a developing set

Santos is a Brazilian port city with high HIV incidence, high primary antiretroviral resistance levels, high HIV-1 BF recombinants prevalence, and high rates of antiretroviral virologic failure. We evaluated factors related to virologic failure after 48 weeks of HAART in this population. We compared demographic and HIV profiles among 43 individuals with virologic failure (group 1) and 37 with virologic success (group 2) after 48 weeks of HAART initiation. The overall primary antiretroviral resistance prevalence was 31.2%; 46.5% in group 1 and 13.5% in group 2 (p?相似文献   

Reduction of HIV-1 in blood and lymph nodes following potent antiretroviral therapy and the virologic correlates of treatment failure

Potent antiretroviral therapy can reduce plasma HIV RNA levels below the threshold of detection for periods of a year or more. The magnitude of HIV RNA reduction in the lymphoid tissue in patients with suppression of HIV RNA levels in plasma beyond 6 months has not been determined. We evaluated levels of HIV RNA and DNA and characterized resistance mutations in blood and inguinal lymph node biopsies obtained from 10 HIV-infected subjects who received 36–52 weeks of indinavir (IDV)/zidovudine (ZDV)/lamivudine (3TC), IDV, or ZDV/3TC. After 1 year of therapy, viral RNA levels in LN of individuals remained detectable but were log₁₀ = 4 lower than in subjects on the triple drug regimen with interruption of therapy or in those treated with ZDV/3TC alone, who had viral loads in their lymph nodes indistinguishable from those expected for untreated patients. In all cases viral DNA remained detectable in lymph nodes and peripheral blood mononuclear cells (PBMC). When plasma virus suppression was incomplete, lymph node and PBMC cultures were positive and drug resistance developed. These studies indicate that pronounced and sustained suppression of plasma viremia by a potent antiretroviral combination is associated with low HIV RNA levels in the lymph nodes 1 year after treatment. Conversely, the persistence of even modest levels of plasma virus after 1 year of treatment reflects ongoing viral replication, the emergence of drug resistance, and the maintenance of high burdens of virus in the lymph nodes.     

云南省2008-2012年HIV-1耐药基因型检测情况

目的了解云南省2008—2012年艾滋病病毒Ⅰ型（HIV-1）耐药基因检测及临床应用情况。方法采用反转录套式聚合酶链反应（RT-nested—PCR）方法,检测病毒抑制失败病人血浆HIV-1耐药基因型。结果截止2012年12月31日,云南省累计治疗艾滋病（AIDS）病人38055人。2008—2012年,HIV1病毒载量（VL）检测率逐年提高（54．0％～95．2％）。HIV-1VL〈50拷贝／mL者占88．7％,VL在51～1000拷贝／mL者占3．4％,VL〉1000拷贝／mL者占7．9％。对VL〉1000拷贝／mL病人血浆进行HIV-1耐药基因突变检测,共检测3766人次,获得可用序列2586例。其中未检出耐药突变的占46．2％（1196／2586）,发生耐药突变的占53．8％（1390／2586）。以2012年末累计治疗人数为基数,计算得到抗病毒治疗（HAART）人群的耐药发生率为3．7％（1390／38055）。16个地市中除丽江和迪庆两地未发现耐药毒株外,其余各地均有不同程度的耐药发生。核苷类反转录酶抑制剂（NRTI）、非核苷类反转录酶抑制剂（NNRTI）和蛋白酶抑制剂（PI）的突变率分别为63．3％、95．1％和8．5％。NRTI突变位点的前3位依次为M184V／I（52．7％）、T215Y／F（11．7％）、D67N（10．2％,）,NNRTI前3位是K103N／S（37．8％）,G190A／S／E（24．4％）,Y181C／I／V（22．0%）,PI出现最多的是L33F,其次还有M46I、V82A。结论云南省抗病毒治疗病毒学失败病人中,以NNRTI耐药最为多见,其次为NRTI,PI较少,各地、市HIV耐药发生存在一定差异。HIV耐药基因检测有助于科学抉择治疗方案,在提高HAART的效果的同时,有效地节约匮乏的药物资源,减少耐药毒株的流行传播。