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Immunodeficiency at the start of combination antiretroviral therapy in low-, middle-, and high-income countries.

ABSTRACT: OBJECTIVE:To describe the CD4 cell count at the start of combination antiretroviral therapy (cART) in low-income (LIC), lower middle-income (LMIC), upper middle-income (UMIC), and high-income (HIC) countries. METHODS:Patients aged 16 years or older starting cART in a clinic participating in a multicohort collaboration spanning 6 continents (International epidemiological Databases to Evaluate AIDS and ART Cohort Collaboration) were eligible. Multilevel linear regression models were adjusted for age, gender, and calendar year; missing CD4 counts were imputed. RESULTS:In total, 379,865 patients from 9 LIC, 4 LMIC, 4 UMIC, and 6 HIC were included. In LIC, the median CD4 cell count at cART initiation increased by 83% from 80 to 145 cells/?L between 2002 and 2009. Corresponding increases in LMIC, UMIC, and HIC were from 87 to 155 cells/?L (76% increase), 88 to 135 cells/?L (53%), and 209 to 274 cells/?L (31%). In 2009, compared with LIC, median counts were 13 cells/?L [95% confidence interval (CI): -56 to +30] lower in LMIC, 22 cells/?L (-62 to +18) lower in UMIC, and 112 cells/?L (+75 to +149) higher in HIC. They were 23 cells/?L (95% CI: +18 to +28 cells/?L) higher in women than men. Median counts were 88 cells/?L (95% CI: +35 to +141 cells/?L) higher in countries with an estimated national cART coverage >80%, compared with countries with <40% coverage. CONCLUSIONS:Median CD4 cell counts at the start of cART increased 2000-2009 but remained below 200 cells/?L in LIC and MIC and below 300 cells/?L in HIC. Earlier start of cART will require substantial efforts and resources globally.

SUBMITTER: IeDEA and ART Cohort Collaborations

PROVIDER: S-EPMC3894575 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Immunodeficiency at the start of combination antiretroviral therapy in low-, middle-, and high-income countries.

Avila Dorita D Althoff Keri N KN Mugglin Catrina C Wools-Kaloustian Kara K Koller Manuel M Dabis François F Nash Denis D Gsponer Thomas T Sungkanuparph Somnuek S McGowan Catherine C May Margaret M Cooper David D Chimbetete Cleophas C Wolff Marcelo M Collier Ann A McManus Hamish H Davies Mary-Ann MA Costagliola Dominique D Crabtree-Ramirez Brenda B Chaiwarith Romanee R Cescon Angela A Cornell Morna M Diero Lameck L Phanuphak Praphan P Sawadogo Adrien A Ehmer Jochen J Eholie Serge P SP Li Patrick C K PC Fox Matthew P MP Gandhi Neel R NR González Elsa E Lee Christopher K C CK Hoffmann Christopher J CJ Kambugu Andrew A Keiser Olivia O Ditangco Rossana R Prozesky Hans H Lampe Fiona F Kumarasamy Nagalingeswaran N Kitahata Mari M Lugina Emmanuel E Lyamuya Rita R Vonthanak Saphonn S Fink Valeria V d'Arminio Monforte Antonella A Luz Paula Mendes PM Chen Yi-Ming A YM Minga Albert A Casabona Jordi J Mwango Albert A Choi Jun Y JY Newell Marie-Louise ML Bukusi Elizabeth A EA Ngonyani Kapella K Merati Tuti P TP Otieno Juliana J Bosco Mwebesa B MB Phiri Sam S Ng Oon T OT Anastos Kathryn K Rockstroh Jürgen J Santos Ignacio I Oka Shinichi S Somi Geoffrey G Stephan Christoph C Teira Ramon R Wabwire Deo D Wandeler Gilles G Boulle Andrew A Reiss Peter P Wood Robin R Chi Benjamin H BH Williams Carolyn C Sterne Jonathan A JA Egger Matthias M

Journal of acquired immune deficiency syndromes (1999) 20140101 1

<h4>Objective</h4>To describe the CD4 cell count at the start of combination antiretroviral therapy (cART) in low-income (LIC), lower middle-income (LMIC), upper middle-income (UMIC), and high-income (HIC) countries.<h4>Methods</h4>Patients aged 16 years or older starting cART in a clinic participating in a multicohort collaboration spanning 6 continents (International epidemiological Databases to Evaluate AIDS and ART Cohort Collaboration) were eligible. Multilevel linear regression models were ...[more]

PMID: 24419071

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Project description:BackgroundAntiretroviral therapy (ART) management is challenging for individuals in resource-limited settings presenting for third-line treatment because of complex resistance patterns, partly due to reduced access to viral load monitoring. We aimed to evaluate use of newer antiretroviral drugs and contemporary management approaches, including population-based sequencing, to select appropriate antiretrovirals, plasma viral load monitoring, and interventions to improve adherence in individuals presenting with second-line viral failure.MethodsA5288 was a phase 4, third-line ART strategy study done at 19 urban sites in ten countries that enrolled adult participants with confirmed plasma HIV-1 RNA (viral load) of 1000 copies per mL or more after more than 24 weeks of protease inhibitor-based second-line ART. The primary objective was to use antiretrovirals (raltegravir, etravirine, and ritonavir-boosted darunavir) and diagnostic monitoring technologies, including viral load, genotyping, and adherence support to achieve viral load suppression (defined as ≤200 copies per mL) in 65% or more of participants. ART history and real-time drug resistance genotypes were used to assign participants to one of four cohorts: cohort A (no lopinavir resistance) stayed on second-line ART and cohorts B (B1, best available nucleoside reverse transcriptase inhibitors [NRTIs] plus ritonavir-boosted darunavir plus raltegravir; B2, ritonavir-boosted darunavir plus raltegravir plus etravirine; B3, ritonavir-boosted darunavir, raltegravir, and either tenofovir plus emtricitabine or tenofovir plus lamivudine), C (ritonavir-boosted darunavir plus raltegravir plus tenofovir-emtricitabine or tenofovir plus lamivudine), and D (best available NRTIs plus ritonavir-boosted darunavir plus raltegravir) were defined by increasing levels of resistance and received appropriate regimens, including new antiretrovirals. Participants in Cohort B without detectable hepatitis B surface antigen were assigned by blocked randomisation to cohorts B1 and B2, and those with detectable hepatitis B surface antigen were assigned to cohort B3. The trial is registered with ClinicalTrials.gov, number NCT01641367.FindingsFrom Jan 10, 2013, to Sept 10, 2015, 545 participants were enrolled. 287 (53%) were assigned to cohort A, 74 (14%) to B1, 72 (13%) to B2, eight (1%) to B3, 70 (13%) to C, and 34 (6%) to D. Overall, 349 (64%, 95% CI 60-68) participants achieved viral suppression at week 48, with proportions varying from 125 (44%) of 287 in cohort A to 65 (88%) of 74 in cohort B1, 63 (88%) of 72 in B2, eight (100%) of eight in B3, 63 (90%) of 70 in C, and 25 (74%) of 34 in D. Participants in cohort A remained on their second-line protease inhibitor, and had the most participants with grade 3 or higher adverse events (147 [51%]).InterpretationTargeted real-time genotyping to select third-line ART can appropriately allocate more costly antiretrovirals to those with greater levels of HIV drug resistance.FundingNational Institutes of Health.

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Immunodeficiency at the start of combination antiretroviral therapy in low-, middle-, and high-income countries.

Publications

Immunodeficiency at the start of combination antiretroviral therapy in low-, middle-, and high-income countries.

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