Anti-retroviral drug resistance-associated mutations among non-subtype B HIV-1-infected Kenyan children with treatment failure
Recently increased availability of anti-retroviral therapy (ART) has mitigated HIV-1/AIDS prognoses especially in resource poor settings. The emergence of ART resistance-associated mutations from non-suppressive ART has been implicated as a major cause of ART failure. Reverse transcriptase inhibitor (RTI)-resistance mutations among 12 non-subtype B HIV-1-infected children with treatment failure were evaluated by genotypically analyzing HIV-1 strains isolated from plasma obtained between 2001 and 2004. A region of pol-RT gene was amplified and at least five clones per sample were analyzed. Phylogenetic analysis revealed HIV-1 subtype A1 (n = 7), subtype C (n = 1), subtype D (n = 3), and CRF02_AG (n = 1). Before treatment, 4 of 12 (33.3%) children had primary RTI-resistance mutations, K103N (n = 3, ages 5-7 years) and Y181C (n = 1, age 1 year). In one child, K103N was found as a minor population (1/5 clones) before treatment and became major (7/7 clones) 8 months after RTI treatment. In 7 of 12 children, M184V appeared with one thymidine-analogue-associated mutation (TAM) as the first mutation, while the remaining 5 children had only TAMs appearing either individually (n = 2), or as TAMs 1 (M41L, L210W, and T215Y) and 2 (D67N, K70R, and K219Q/E/R) appearing together (n = 3). These results suggest that "vertically transmitted" primary RTI-resistance mutations, K103N and Y181C, can persist over the years even in the absence of drug pressure and impact RTI treatment negatively, and that appearing patterns of RTI-resistance mutations among non-subtype B HIV-1-infected children could possibly be different from those reported in subtype B-infected children.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2007 |
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| Erschienen: |
2007 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:79 |
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| Enthalten in: |
Journal of medical virology - 79(2007), 7 vom: 01. Juli, Seite 865-72 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lwembe, Raphael [VerfasserIn] |
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| Themen: |
Anti-HIV Agents |
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| Anmerkungen: |
Date Completed 07.08.2007 Date Revised 18.03.2022 published: Print GENBANK: DQ679541, DQ679542, DQ679543, DQ679544, DQ679545, DQ679546, DQ679547, DQ679548, DQ679549, DQ679550, DQ679551, DQ679552, DQ679553, DQ679554, DQ679555, DQ679556, DQ679557, DQ679558, DQ679559, DQ679560, DQ679561, DQ679562, DQ679563, DQ679564, DQ679565, DQ679566, DQ679567, DQ679568, DQ679569, DQ679570, DQ679571, DQ679572, DQ679573, DQ679574, DQ679575, DQ679576, DQ679577, DQ679578, DQ679579, DQ679580, DQ679581, DQ679582, DQ679583, DQ679584, DQ679585, DQ679586, DQ679587, DQ679588, DQ679589, DQ679590, DQ679591, DQ679592, DQ679593, DQ679594, DQ679595, DQ679596, DQ679597, DQ679598, DQ679599, DQ679600, DQ679601, DQ679602, DQ679603, DQ679604, DQ679605, DQ679606, DQ679607, DQ679608, DQ679609, DQ679610, DQ679611, DQ679612, DQ679613, DQ679614, DQ679615, DQ679616, DQ679617, DQ679618, DQ679619, DQ679620, DQ679621, DQ679622, DQ679623, DQ679624, DQ679625, DQ679626, DQ679627, DQ679628, DQ679629, DQ679630, DQ679631, DQ679632, DQ679633, DQ679634, DQ679635, DQ679636, DQ679637, DQ679638, DQ679639, DQ679640, DQ679641, DQ679642, DQ679643, DQ679644, DQ679645, DQ679646, DQ679647, DQ679648, DQ679649, DQ679650, DQ679651, DQ679652, DQ679653, DQ679654, DQ679655, DQ679656, DQ679657, DQ679658, DQ679659, DQ679660, DQ679661, DQ679662, DQ679663, DQ679664, DQ679665, DQ679666, DQ679667, DQ679668, DQ679669, DQ679670, DQ679671, DQ679672, DQ679673, DQ679674, DQ679675, DQ679676, DQ679677, DQ679678, DQ679679, DQ679680, DQ679681, DQ679682, DQ679683, DQ679684, DQ679685, DQ679686, DQ679687, DQ679688, DQ679689, DQ679690, DQ679691, DQ679692, DQ679693, DQ679694, DQ679695, DQ679696, DQ679697, DQ679698, DQ679699, DQ679700, DQ679701, DQ679702, DQ679703, DQ679704, DQ679705, DQ679706, DQ679707, DQ679708, DQ679709, DQ679710, DQ679711, DQ679712, DQ679713, DQ679714, DQ679715, DQ679716, DQ679717, DQ679718, DQ679719, DQ679720, DQ679721, DQ679722, DQ679723, DQ679724, DQ679725, DQ679726, DQ679727, DQ679728, DQ679729, DQ679730, DQ679731, DQ679732, DQ679733, DQ679734, DQ679735, DQ679736, DQ679737, DQ679738, DQ679739, DQ679740, DQ679741, DQ679742, DQ679743, DQ679744, DQ679745, DQ679746, DQ679747, DQ679748, DQ679749, DQ679750, DQ679751, DQ679752, DQ679753 Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM170421104 |
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| 041 | |a eng | ||
| 100 | 1 | |a Lwembe, Raphael |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Anti-retroviral drug resistance-associated mutations among non-subtype B HIV-1-infected Kenyan children with treatment failure |
| 264 | 1 | |c 2007 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 07.08.2007 | ||
| 500 | |a Date Revised 18.03.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a GENBANK: DQ679541, DQ679542, DQ679543, DQ679544, DQ679545, DQ679546, DQ679547, DQ679548, DQ679549, DQ679550, DQ679551, DQ679552, DQ679553, DQ679554, DQ679555, DQ679556, DQ679557, DQ679558, DQ679559, DQ679560, DQ679561, DQ679562, DQ679563, DQ679564, DQ679565, DQ679566, DQ679567, DQ679568, DQ679569, DQ679570, DQ679571, DQ679572, DQ679573, DQ679574, DQ679575, DQ679576, DQ679577, DQ679578, DQ679579, DQ679580, DQ679581, DQ679582, DQ679583, DQ679584, DQ679585, DQ679586, DQ679587, DQ679588, DQ679589, DQ679590, DQ679591, DQ679592, DQ679593, DQ679594, DQ679595, DQ679596, DQ679597, DQ679598, DQ679599, DQ679600, DQ679601, DQ679602, DQ679603, DQ679604, DQ679605, DQ679606, DQ679607, DQ679608, DQ679609, DQ679610, DQ679611, DQ679612, DQ679613, DQ679614, DQ679615, DQ679616, DQ679617, DQ679618, DQ679619, DQ679620, DQ679621, DQ679622, DQ679623, DQ679624, DQ679625, DQ679626, DQ679627, DQ679628, DQ679629, DQ679630, DQ679631, DQ679632, DQ679633, DQ679634, DQ679635, DQ679636, DQ679637, DQ679638, DQ679639, DQ679640, DQ679641, DQ679642, DQ679643, DQ679644, DQ679645, DQ679646, DQ679647, DQ679648, DQ679649, DQ679650, DQ679651, DQ679652, DQ679653, DQ679654, DQ679655, DQ679656, DQ679657, DQ679658, DQ679659, DQ679660, DQ679661, DQ679662, DQ679663, DQ679664, DQ679665, DQ679666, DQ679667, DQ679668, DQ679669, DQ679670, DQ679671, DQ679672, DQ679673, DQ679674, DQ679675, DQ679676, DQ679677, DQ679678, DQ679679, DQ679680, DQ679681, DQ679682, DQ679683, DQ679684, DQ679685, DQ679686, DQ679687, DQ679688, DQ679689, DQ679690, DQ679691, DQ679692, DQ679693, DQ679694, DQ679695, DQ679696, DQ679697, DQ679698, DQ679699, DQ679700, DQ679701, DQ679702, DQ679703, DQ679704, DQ679705, DQ679706, DQ679707, DQ679708, DQ679709, DQ679710, DQ679711, DQ679712, DQ679713, DQ679714, DQ679715, DQ679716, DQ679717, DQ679718, DQ679719, DQ679720, DQ679721, DQ679722, DQ679723, DQ679724, DQ679725, DQ679726, DQ679727, DQ679728, DQ679729, DQ679730, DQ679731, DQ679732, DQ679733, DQ679734, DQ679735, DQ679736, DQ679737, DQ679738, DQ679739, DQ679740, DQ679741, DQ679742, DQ679743, DQ679744, DQ679745, DQ679746, DQ679747, DQ679748, DQ679749, DQ679750, DQ679751, DQ679752, DQ679753 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Recently increased availability of anti-retroviral therapy (ART) has mitigated HIV-1/AIDS prognoses especially in resource poor settings. The emergence of ART resistance-associated mutations from non-suppressive ART has been implicated as a major cause of ART failure. Reverse transcriptase inhibitor (RTI)-resistance mutations among 12 non-subtype B HIV-1-infected children with treatment failure were evaluated by genotypically analyzing HIV-1 strains isolated from plasma obtained between 2001 and 2004. A region of pol-RT gene was amplified and at least five clones per sample were analyzed. Phylogenetic analysis revealed HIV-1 subtype A1 (n = 7), subtype C (n = 1), subtype D (n = 3), and CRF02_AG (n = 1). Before treatment, 4 of 12 (33.3%) children had primary RTI-resistance mutations, K103N (n = 3, ages 5-7 years) and Y181C (n = 1, age 1 year). In one child, K103N was found as a minor population (1/5 clones) before treatment and became major (7/7 clones) 8 months after RTI treatment. In 7 of 12 children, M184V appeared with one thymidine-analogue-associated mutation (TAM) as the first mutation, while the remaining 5 children had only TAMs appearing either individually (n = 2), or as TAMs 1 (M41L, L210W, and T215Y) and 2 (D67N, K70R, and K219Q/E/R) appearing together (n = 3). These results suggest that "vertically transmitted" primary RTI-resistance mutations, K103N and Y181C, can persist over the years even in the absence of drug pressure and impact RTI treatment negatively, and that appearing patterns of RTI-resistance mutations among non-subtype B HIV-1-infected children could possibly be different from those reported in subtype B-infected children | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Anti-HIV Agents |2 NLM | |
| 650 | 7 | |a RNA, Viral |2 NLM | |
| 650 | 7 | |a Reverse Transcriptase Inhibitors |2 NLM | |
| 700 | 1 | |a Ochieng, Washingtone |e verfasserin |4 aut | |
| 700 | 1 | |a Panikulam, Annie |e verfasserin |4 aut | |
| 700 | 1 | |a Mongoina, Charles O |e verfasserin |4 aut | |
| 700 | 1 | |a Palakudy, Tresa |e verfasserin |4 aut | |
| 700 | 1 | |a Koizumi, Yusuke |e verfasserin |4 aut | |
| 700 | 1 | |a Kageyama, Seiji |e verfasserin |4 aut | |
| 700 | 1 | |a Yamamoto, Naohiko |e verfasserin |4 aut | |
| 700 | 1 | |a Shioda, Tatsuo |e verfasserin |4 aut | |
| 700 | 1 | |a Musoke, Rachel |e verfasserin |4 aut | |
| 700 | 1 | |a Owens, Mary |e verfasserin |4 aut | |
| 700 | 1 | |a Songok, Elijah M |e verfasserin |4 aut | |
| 700 | 1 | |a Okoth, Frederick A |e verfasserin |4 aut | |
| 700 | 1 | |a Ichimura, Hiroshi |e verfasserin |4 aut | |
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| 773 | 1 | 8 | |g volume:79 |g year:2007 |g number:7 |g day:01 |g month:07 |g pages:865-72 |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 79 |j 2007 |e 7 |b 01 |c 07 |h 865-72 | ||