Date of download: 6/27/2016 Copyright © 2016 American Medical Association. All rights reserved. From: HIV-1 Drug Resistance Profiles in Children and Adults With Viral Load of <50 Copies/mL Receiving Combination Therapy JAMA. 2001;286(2): doi: /jama HAART indicates highly active antiretroviral therapy; HIV-1, humanimmunodeficiency virus type 1. Plasma virus levels in patients from whom theHIV-1 pol gene was successfully amplified from low-levelplasma virus. Open symbols indicate that the level of plasma viremia was belowthe limit of detection of the assay used (400, 200, or 50 copies/mL); theseplotted points are not actual values but serve to indicate the limit of detection.Except for patient C11, plasma virus levels were at or below the limits ofdetection of the ultrasensitive assay (50 copies/mL) at the time of amplification(arrows) (patient C22 had a blip to 64 copies/mL at the third amplification). Figure Legend:

Date of download: 6/27/2016 Copyright © 2016 American Medical Association. All rights reserved. From: HIV-1 Drug Resistance Profiles in Children and Adults With Viral Load of <50 Copies/mL Receiving Combination Therapy JAMA. 2001;286(2): doi: /jama HAART indicates highly active antiretroviral therapy; HIV-1, humanimmunodeficiency virus type 1; AZT, zidovudine; ddI, didanosine; 3TC, lamivudine;d4T, stavudine; ABC, abacavir; DLV, delavirdine; EFV, efavirenz; RTV, ritonavir;NFV, nelfinavir; SQV, saquinavir; and IDV, indinavir. For protease drug resistancecolor codes, see Figure 3. Accessory mutation refers to a genetic variantthat alone does not confer high-level resistance but can occur in associationwith resistance mutations and may contribute to resistance or viral fitness.*Indicates insertion sequences. Figure Legend:

Date of download: 6/27/2016 Copyright © 2016 American Medical Association. All rights reserved. From: HIV-1 Drug Resistance Profiles in Children and Adults With Viral Load of <50 Copies/mL Receiving Combination Therapy JAMA. 2001;286(2): doi: /jama For expansion of terms, see Figure 2 legend. Figure Legend:

Date of download: 6/27/2016 Copyright © 2016 American Medical Association. All rights reserved. From: HIV-1 Drug Resistance Profiles in Children and Adults With Viral Load of <50 Copies/mL Receiving Combination Therapy JAMA. 2001;286(2): doi: /jama Tree shows relationships of plasma (labeled boxes) and latent reservoir(dots) sequences of 9 study patients. Bars to the right of the latent reservoirsequences indicate the number of months between sampling of the latent reservoirand the plasma (P). For 7 patients, previously determinedsequences of virus in the latent reservoir were available, permitting comparisonwith plasma sequences from the same patient. Latent reservoir sequences fromthese patients were obtained from clones of replication- competent virus isolatedfrom resting CD4+ T cells at earlier time points. Numbers aboveinternal nodes indicate the percentage of 1000 bootstrap replicates that supportedthe branch. Only values greater than 70% are indicated (conventionally acceptedas indicating a true clustering of sequences); these branches were supportedby all 3 models of phylogenetic inference applied (neighbor-joining, maximumparsimony, and maximum likelihood). The maximum likelihood tree is shown.The reference sequence HXB2 (GenBank accession No. K03455) was used as anoutgroup (reference sequence known to be unlinked to sequences under study).HAART indicates highly active antiretroviral therapy. The scale indicatesthe expected number of substitutions per site. Figure Legend:

Date of download: 6/27/2016 Copyright © 2016 American Medical Association. All rights reserved. From: HIV-1 Drug Resistance Profiles in Children and Adults With Viral Load of <50 Copies/mL Receiving Combination Therapy JAMA. 2001;286(2): doi: /jama Detailed analysis of sequences from patient A9. Sequences from thelatent reservoir of patient A9 obtained at 6 separate time points commingled with one another and with current plasmasequences, consistent with an absence of time-dependent evolution. Four maingroups of sequences can be discerned based on the presence of resistance mutationsto zidovudine and ritonavir. One plasma clone (4.4) lacked any drug resistancemutations and showed a close phylogenetic relationship to a large group ofpreviously isolated wild-type sequences present in the latent reservoir. Two other plasma clones (4.12 and 7.1) had a V82Fsubstitution in protease and clustered with previously isolated latent reservoirsequences bearing the same mutation. Phenotypic analysis revealed only marginalresistance to ritonavir. A final plasma clone (1.1) had the characteristicV82A, I54V, V77I, and L63P mutations that confer high-level resistance toritonavir. This clone clustered with a group of previously isolated latentreservoir sequences bearing the same mutations and having a high level ofphenotypic resistance to ritonavir. The clone c (see Figure 4) was includedfor purposes of comparison. The scale indicates the expected number of substitutionsper site. Figure Legend: