Drug Resistance in Human Immunodeficiency Virus Type-1 Infected Zambian Children Using Adult Fixed Dose Combination Stavudine, Lamivudine, and Nevirapine
BACKGROUND:There are few medium-term virologic data in children from resource-limited settings taking adult fixed-dose-combination antiretroviral therapy (cART) without viral load monitoring. METHODS:CHAP2 (Children with HIV Antibiotic Prophylaxis 2) is a prospective cohort of Zambian children using...
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| creator | Gupta, Ravindra K Ford, Deborah Mulenga, Veronica Walker, A Sarah Kabamba, Desire Kalumbi, Moxmalama Grant, Paul R Ferrier, Alexander Pillay, Deenan Gibb, Diana M Chintu, Chifumbe |
| description | BACKGROUND:There are few medium-term virologic data in children from resource-limited settings taking adult fixed-dose-combination antiretroviral therapy (cART) without viral load monitoring.
METHODS:CHAP2 (Children with HIV Antibiotic Prophylaxis 2) is a prospective cohort of Zambian children using d4T/3TC/NVP adult Triomune30 dosed according to WHO guidelines.
RESULTS:A total of 103 children (19 with previous antiretroviral therapy) had follow-up >6 months. Median age at cART initiation was 8 years (IQR, 6–12) and CD4 8% (4–12). At 24 months, CD4% had increased by a median of 15% (7–25). For 74 children viral load was known/inferred51 of 74 (69%) had viral load 1000 copies/mL. Of 26 children with resistance data, 25 (96%) had NNRTI resistance; 22 (84%) had M184V; 2 (8%) had Q151M; and 1 (4%) each had K65R, L74V, or K70E. Eight (31%) had ≥1 TAM. Those failing virologically with a genotypic sensitivity score of 0 for first-line therapy had a somewhat smaller increase in CD4% from baseline compared with those failing therapy with a genotypic sensitivity score >0 (+3 vs. +8, P = 0.13), and had somewhat lower CD4% at initiation of cART (2 vs. 11, P = 0.09). In 6 children with >1 resistance test, the estimated rate of accumulation of TAMs was 0.59/yr (95% confidence interval0.22–1.29).
CONCLUSIONS:Twenty-four month virologic responses to cART were good. However, the rate of TAM accumulation in those with rebound was higher than reported in Western adult cohorts, and there was some indication of a detrimental effect of high level resistance on CD4% change from baseline. |
| doi_str_mv | 10.1097/INF.0b013e3181e47609 |
| format | Article |
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METHODS:CHAP2 (Children with HIV Antibiotic Prophylaxis 2) is a prospective cohort of Zambian children using d4T/3TC/NVP adult Triomune30 dosed according to WHO guidelines.
RESULTS:A total of 103 children (19 with previous antiretroviral therapy) had follow-up >6 months. Median age at cART initiation was 8 years (IQR, 6–12) and CD4 8% (4–12). At 24 months, CD4% had increased by a median of 15% (7–25). For 74 children viral load was known/inferred51 of 74 (69%) had viral load <50 copies/mL (45 of 63 [71%] with no previous cART, 6 of 11 [55%] with previous cART; difference P = 0.30); 22 of 74 (30%) had viral load >1000 copies/mL. Of 26 children with resistance data, 25 (96%) had NNRTI resistance; 22 (84%) had M184V; 2 (8%) had Q151M; and 1 (4%) each had K65R, L74V, or K70E. Eight (31%) had ≥1 TAM. Those failing virologically with a genotypic sensitivity score of 0 for first-line therapy had a somewhat smaller increase in CD4% from baseline compared with those failing therapy with a genotypic sensitivity score >0 (+3 vs. +8, P = 0.13), and had somewhat lower CD4% at initiation of cART (2 vs. 11, P = 0.09). In 6 children with >1 resistance test, the estimated rate of accumulation of TAMs was 0.59/yr (95% confidence interval0.22–1.29).
CONCLUSIONS:Twenty-four month virologic responses to cART were good. However, the rate of TAM accumulation in those with rebound was higher than reported in Western adult cohorts, and there was some indication of a detrimental effect of high level resistance on CD4% change from baseline.</description><identifier>ISSN: 0891-3668</identifier><identifier>EISSN: 1532-0987</identifier><identifier>DOI: 10.1097/INF.0b013e3181e47609</identifier><identifier>PMID: 20508547</identifier><language>eng</language><publisher>United States: Lippincott Williams & Wilkins, Inc</publisher><subject>Amino Acid Substitution - genetics ; Anti-HIV Agents - administration & dosage ; Anti-HIV Agents - pharmacology ; CD4 Lymphocyte Count ; Child ; Child, Preschool ; Cohort Studies ; Drug Monitoring ; Drug Resistance, Viral ; Female ; Follow-Up Studies ; HIV Infections - drug therapy ; HIV Infections - virology ; HIV-1 - drug effects ; HIV-1 - isolation & purification ; Humans ; Lamivudine - administration & dosage ; Lamivudine - pharmacology ; Male ; Mutation, Missense ; Nevirapine - administration & dosage ; Nevirapine - pharmacology ; Prospective Studies ; Stavudine - administration & dosage ; Stavudine - pharmacology ; Treatment Failure ; Viral Load ; Viral Proteins - genetics ; Zambia</subject><ispartof>The Pediatric infectious disease journal, 2010-08, Vol.29 (8), p.e57-e62</ispartof><rights>2010 Lippincott Williams & Wilkins, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3513-cb8fa1d00e52ec30b8e3bfdad32760d66f3c2c9a0dd4fc7a2c41591f548cf8603</citedby><cites>FETCH-LOGICAL-c3513-cb8fa1d00e52ec30b8e3bfdad32760d66f3c2c9a0dd4fc7a2c41591f548cf8603</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20508547$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gupta, Ravindra K</creatorcontrib><creatorcontrib>Ford, Deborah</creatorcontrib><creatorcontrib>Mulenga, Veronica</creatorcontrib><creatorcontrib>Walker, A Sarah</creatorcontrib><creatorcontrib>Kabamba, Desire</creatorcontrib><creatorcontrib>Kalumbi, Moxmalama</creatorcontrib><creatorcontrib>Grant, Paul R</creatorcontrib><creatorcontrib>Ferrier, Alexander</creatorcontrib><creatorcontrib>Pillay, Deenan</creatorcontrib><creatorcontrib>Gibb, Diana M</creatorcontrib><creatorcontrib>Chintu, Chifumbe</creatorcontrib><title>Drug Resistance in Human Immunodeficiency Virus Type-1 Infected Zambian Children Using Adult Fixed Dose Combination Stavudine, Lamivudine, and Nevirapine</title><title>The Pediatric infectious disease journal</title><addtitle>Pediatr Infect Dis J</addtitle><description>BACKGROUND:There are few medium-term virologic data in children from resource-limited settings taking adult fixed-dose-combination antiretroviral therapy (cART) without viral load monitoring.
METHODS:CHAP2 (Children with HIV Antibiotic Prophylaxis 2) is a prospective cohort of Zambian children using d4T/3TC/NVP adult Triomune30 dosed according to WHO guidelines.
RESULTS:A total of 103 children (19 with previous antiretroviral therapy) had follow-up >6 months. Median age at cART initiation was 8 years (IQR, 6–12) and CD4 8% (4–12). At 24 months, CD4% had increased by a median of 15% (7–25). For 74 children viral load was known/inferred51 of 74 (69%) had viral load <50 copies/mL (45 of 63 [71%] with no previous cART, 6 of 11 [55%] with previous cART; difference P = 0.30); 22 of 74 (30%) had viral load >1000 copies/mL. Of 26 children with resistance data, 25 (96%) had NNRTI resistance; 22 (84%) had M184V; 2 (8%) had Q151M; and 1 (4%) each had K65R, L74V, or K70E. Eight (31%) had ≥1 TAM. Those failing virologically with a genotypic sensitivity score of 0 for first-line therapy had a somewhat smaller increase in CD4% from baseline compared with those failing therapy with a genotypic sensitivity score >0 (+3 vs. +8, P = 0.13), and had somewhat lower CD4% at initiation of cART (2 vs. 11, P = 0.09). In 6 children with >1 resistance test, the estimated rate of accumulation of TAMs was 0.59/yr (95% confidence interval0.22–1.29).
CONCLUSIONS:Twenty-four month virologic responses to cART were good. However, the rate of TAM accumulation in those with rebound was higher than reported in Western adult cohorts, and there was some indication of a detrimental effect of high level resistance on CD4% change from baseline.</description><subject>Amino Acid Substitution - genetics</subject><subject>Anti-HIV Agents - administration & dosage</subject><subject>Anti-HIV Agents - pharmacology</subject><subject>CD4 Lymphocyte Count</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Cohort Studies</subject><subject>Drug Monitoring</subject><subject>Drug Resistance, Viral</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - virology</subject><subject>HIV-1 - drug effects</subject><subject>HIV-1 - isolation & purification</subject><subject>Humans</subject><subject>Lamivudine - administration & dosage</subject><subject>Lamivudine - pharmacology</subject><subject>Male</subject><subject>Mutation, Missense</subject><subject>Nevirapine - administration & dosage</subject><subject>Nevirapine - pharmacology</subject><subject>Prospective Studies</subject><subject>Stavudine - administration & dosage</subject><subject>Stavudine - pharmacology</subject><subject>Treatment Failure</subject><subject>Viral Load</subject><subject>Viral Proteins - genetics</subject><subject>Zambia</subject><issn>0891-3668</issn><issn>1532-0987</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc1O3DAUha2qVRmgb1BVfgAC17GTOEs0MDDSCKQCXXQTOfY145I4IzsB5lF4W4z4k7q690jnnMV3CPnJ4JBBXR0tLxaH0ALjyJlkKKoS6i9kxgqeZ1DL6iuZgaxZxstS7pDdGP8BABcMvpOdHAqQhahm5OkkTLf0N0YXR-U1Uufp-dQrT5d9P_nBoHXaoddb-seFKdLr7QYzRpfeoh7R0L-qb12yz9euMwE9vYnO39JjM3UjXbjHZDkZItL5kHxejW7w9GpU95NxHg_oSvXu_Vfe0Au8d0Ftkt4n36zqIv54u3vkZnF6PT_PVpdny_nxKtO8YDzTrbSKGQAsctQcWom8tUYZnicipiwt17muFRgjrK5UrgUramYLIbWVJfA9Il57dRhiDGibTXC9CtuGQfNCukmkm_9Jp9iv19hmans0H6F3tJ-9D0M3Yoh33fSAoVmj6sZ1k7aAUhQiy4EByKSyl3k4fwZTrIy4</recordid><startdate>201008</startdate><enddate>201008</enddate><creator>Gupta, Ravindra K</creator><creator>Ford, Deborah</creator><creator>Mulenga, Veronica</creator><creator>Walker, A Sarah</creator><creator>Kabamba, Desire</creator><creator>Kalumbi, Moxmalama</creator><creator>Grant, Paul R</creator><creator>Ferrier, Alexander</creator><creator>Pillay, Deenan</creator><creator>Gibb, Diana M</creator><creator>Chintu, Chifumbe</creator><general>Lippincott Williams & Wilkins, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>201008</creationdate><title>Drug Resistance in Human Immunodeficiency Virus Type-1 Infected Zambian Children Using Adult Fixed Dose Combination Stavudine, Lamivudine, and Nevirapine</title><author>Gupta, Ravindra K ; Ford, Deborah ; Mulenga, Veronica ; Walker, A Sarah ; Kabamba, Desire ; Kalumbi, Moxmalama ; Grant, Paul R ; Ferrier, Alexander ; Pillay, Deenan ; Gibb, Diana M ; Chintu, Chifumbe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3513-cb8fa1d00e52ec30b8e3bfdad32760d66f3c2c9a0dd4fc7a2c41591f548cf8603</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Amino Acid Substitution - genetics</topic><topic>Anti-HIV Agents - administration & dosage</topic><topic>Anti-HIV Agents - pharmacology</topic><topic>CD4 Lymphocyte Count</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Cohort Studies</topic><topic>Drug Monitoring</topic><topic>Drug Resistance, Viral</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Infections - virology</topic><topic>HIV-1 - drug effects</topic><topic>HIV-1 - isolation & purification</topic><topic>Humans</topic><topic>Lamivudine - administration & dosage</topic><topic>Lamivudine - pharmacology</topic><topic>Male</topic><topic>Mutation, Missense</topic><topic>Nevirapine - administration & dosage</topic><topic>Nevirapine - pharmacology</topic><topic>Prospective Studies</topic><topic>Stavudine - administration & dosage</topic><topic>Stavudine - pharmacology</topic><topic>Treatment Failure</topic><topic>Viral Load</topic><topic>Viral Proteins - genetics</topic><topic>Zambia</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gupta, Ravindra K</creatorcontrib><creatorcontrib>Ford, Deborah</creatorcontrib><creatorcontrib>Mulenga, Veronica</creatorcontrib><creatorcontrib>Walker, A Sarah</creatorcontrib><creatorcontrib>Kabamba, Desire</creatorcontrib><creatorcontrib>Kalumbi, Moxmalama</creatorcontrib><creatorcontrib>Grant, Paul R</creatorcontrib><creatorcontrib>Ferrier, Alexander</creatorcontrib><creatorcontrib>Pillay, Deenan</creatorcontrib><creatorcontrib>Gibb, Diana M</creatorcontrib><creatorcontrib>Chintu, Chifumbe</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>The Pediatric infectious disease journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gupta, Ravindra K</au><au>Ford, Deborah</au><au>Mulenga, Veronica</au><au>Walker, A Sarah</au><au>Kabamba, Desire</au><au>Kalumbi, Moxmalama</au><au>Grant, Paul R</au><au>Ferrier, Alexander</au><au>Pillay, Deenan</au><au>Gibb, Diana M</au><au>Chintu, Chifumbe</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Drug Resistance in Human Immunodeficiency Virus Type-1 Infected Zambian Children Using Adult Fixed Dose Combination Stavudine, Lamivudine, and Nevirapine</atitle><jtitle>The Pediatric infectious disease journal</jtitle><addtitle>Pediatr Infect Dis J</addtitle><date>2010-08</date><risdate>2010</risdate><volume>29</volume><issue>8</issue><spage>e57</spage><epage>e62</epage><pages>e57-e62</pages><issn>0891-3668</issn><eissn>1532-0987</eissn><abstract>BACKGROUND:There are few medium-term virologic data in children from resource-limited settings taking adult fixed-dose-combination antiretroviral therapy (cART) without viral load monitoring.
METHODS:CHAP2 (Children with HIV Antibiotic Prophylaxis 2) is a prospective cohort of Zambian children using d4T/3TC/NVP adult Triomune30 dosed according to WHO guidelines.
RESULTS:A total of 103 children (19 with previous antiretroviral therapy) had follow-up >6 months. Median age at cART initiation was 8 years (IQR, 6–12) and CD4 8% (4–12). At 24 months, CD4% had increased by a median of 15% (7–25). For 74 children viral load was known/inferred51 of 74 (69%) had viral load <50 copies/mL (45 of 63 [71%] with no previous cART, 6 of 11 [55%] with previous cART; difference P = 0.30); 22 of 74 (30%) had viral load >1000 copies/mL. Of 26 children with resistance data, 25 (96%) had NNRTI resistance; 22 (84%) had M184V; 2 (8%) had Q151M; and 1 (4%) each had K65R, L74V, or K70E. Eight (31%) had ≥1 TAM. Those failing virologically with a genotypic sensitivity score of 0 for first-line therapy had a somewhat smaller increase in CD4% from baseline compared with those failing therapy with a genotypic sensitivity score >0 (+3 vs. +8, P = 0.13), and had somewhat lower CD4% at initiation of cART (2 vs. 11, P = 0.09). In 6 children with >1 resistance test, the estimated rate of accumulation of TAMs was 0.59/yr (95% confidence interval0.22–1.29).
CONCLUSIONS:Twenty-four month virologic responses to cART were good. However, the rate of TAM accumulation in those with rebound was higher than reported in Western adult cohorts, and there was some indication of a detrimental effect of high level resistance on CD4% change from baseline.</abstract><cop>United States</cop><pub>Lippincott Williams & Wilkins, Inc</pub><pmid>20508547</pmid><doi>10.1097/INF.0b013e3181e47609</doi></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0891-3668 |
| ispartof | The Pediatric infectious disease journal, 2010-08, Vol.29 (8), p.e57-e62 |
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| source | MEDLINE; Journals@Ovid Complete |
| subjects | Amino Acid Substitution - genetics Anti-HIV Agents - administration & dosage Anti-HIV Agents - pharmacology CD4 Lymphocyte Count Child Child, Preschool Cohort Studies Drug Monitoring Drug Resistance, Viral Female Follow-Up Studies HIV Infections - drug therapy HIV Infections - virology HIV-1 - drug effects HIV-1 - isolation & purification Humans Lamivudine - administration & dosage Lamivudine - pharmacology Male Mutation, Missense Nevirapine - administration & dosage Nevirapine - pharmacology Prospective Studies Stavudine - administration & dosage Stavudine - pharmacology Treatment Failure Viral Load Viral Proteins - genetics Zambia |
| title | Drug Resistance in Human Immunodeficiency Virus Type-1 Infected Zambian Children Using Adult Fixed Dose Combination Stavudine, Lamivudine, and Nevirapine |
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