Dataset Information

Zimbabwe's national third-line antiretroviral therapy program: Cohort description and treatment outcomes.

ABSTRACT: BACKGROUND:In 2015, Zimbabwe introduced third-line antiretroviral therapy (ART) through four designated treatment centers; three government clinics in Harare and Bulawayo, and Newlands Clinic (NC), operated by a private voluntary organization in Harare. We describe characteristics of patients receiving third line ART and analyzed treatment outcomes in this national programme as of 31 December 2018. METHODS:We described the population using proportions for categorical variables, and medians and interquartile ranges for continuous variables. Patients from NC, where data were more complete, were followed from the date of starting third-line ART until death, transfer, loss to follow up or 31 December 2018. RESULTS:A total of 209 patients had ever received third-line ART: 124 at NC and 85 from the three government clinics. HIV genotype results were available for 89 (72%) patients at NC and fourteen (16.5%) patients in the government clinics. Median duration of third line ART (years) in the government clinics was 2.3 (IQR:0.6-3.4), 1.3 (IQR: 0.7-1.7) and 1 (0.6-1.9). Of the 67 patients who received third line ART in the government clinics for at least six months, 53 (79%) had most recent viral load (VL) < 1000 copies/ml. Data on other treatment outcomes from government clinics were incomplete. From NC: a total of 109 (88%) patients were still in care, 13 (10.5%) had died and 2 (1.5%) were transferred. Median duration of third-line ART was 1.4 years (IQR: 0.6-2.8). Among the 111 NC patients who had received third-line ART for at least 6 months, 83 (75%) had a VL <50 copies/ml and 106 (95.5%) had a VL <1000 copies/ml. CONCLUSION:Our findings demonstrate that, with comprehensive care, patients failing second-line ART can achieve high rates of virological suppression on third-line regimens. There is need to decentralize the provision of third-line ART in Zimbabwe. More needs to be done to improve completeness of data in the government clinics.

SUBMITTER: Chimbetete C

PROVIDER: S-EPMC7051055 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Zimbabwe's national third-line antiretroviral therapy program: Cohort description and treatment outcomes.

Chimbetete Cleophas C Shamu Tinei T Keiser Olivia O

PloS one 20200302 3

<h4>Background</h4>In 2015, Zimbabwe introduced third-line antiretroviral therapy (ART) through four designated treatment centers; three government clinics in Harare and Bulawayo, and Newlands Clinic (NC), operated by a private voluntary organization in Harare. We describe characteristics of patients receiving third line ART and analyzed treatment outcomes in this national programme as of 31 December 2018.<h4>Methods</h4>We described the population using proportions for categorical variables, an ...[more]

PMID: 32119663

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Project description:BACKGROUND:The last evaluation to assess outcomes for patients receiving antiretroviral therapy (ART) through the Zimbabwe public sector was conducted in 2011, covering the 2007-2010 cohorts. The reported retention at 6, 12, 24 and 36 months were 90.7%, 78.1%, 68.8% and 64.4%, respectively. We report findings of a follow-up evaluation for the 2012-2015 cohorts to assess the implementation and impact of recommendations from this prior evaluation. METHODS:A nationwide retrospective study was conducted in 2016. Multi-stage proportional sampling was used to select health facilities and study participants records. The data extracted from patient manual records included demographic, baseline clinical characteristics and patient outcomes (active on treatment, died, transferred out, stopped ART and lost to follow-up (LTFU)) at 6, 12, 24 and 36 months. The data were analysed using Stata/IC 14.2. Retention was estimated using survival analysis. The predictors associated with attrition were determined using a multivariate Cox regression model. RESULTS:A total of 3,810 participants were recruited in the study. The median age in years was 35 (IQR: 28-42). Overall, retention increased to 92.4% (p-value = 0.060), 86.5% (p-value<0.001), 79.2% (p-value<0.001) and 74.4% (p-value<0.001) at 6, 12, 24 and 36 months respectively. LTFU accounted for 98% of attrition. Being an adolescent or a young adult (15-24 years) (vs adult;1.41; 95% CI:1.14-1.74), children (<15years) (vs adults; aHR 0.64; 95% CI:0.46-0.91), receiving care at primary health care facility (vs central and provincial facility; aHR 1.23; 95% CI:1.01-1.49), having initiated ART between 2014-2015 (vs 2012-2013; aHR1.45; 95%CI:1.24-1.69), having WHO Stage IV (vs Stage I-III; aHR2.06; 95%CI:1.51-2.81) and impaired functional status (vs normal status; aHR1.25; 95%CI:1.04-1.49) predicted attrition. CONCLUSION:The overall retention was higher in comparison to the previous 2007-2010 evaluation. Further studies to understand why attrition was found to be higher at primary health care facilities are warranted. Implementation of strategies for managing patients with advanced HIV disease, differentiated care for adolescents and young adults and tracking of LTFU clients should be prioritised to further improve retention.

Project description:IntroductionLimited data describe outcomes on second-line antiretroviral therapy (ART) among children globally. Our objective was to contribute data on outcomes among children living with HIV after initiation of second-line ART in the context of routine care within a large global cohort collaboration.MethodsPatient-level data from 1993 through 2015 from 11 paediatric HIV cohorts were pooled. Characteristics at switch and through two years of follow-up were summarized for children who switched to second-line ART after starting a standard first-line regimen in North America, Latin America, Europe, Asia, Southern Africa (South Africa & Botswana) and the rest of sub-Saharan Africa (SSA). Cumulative incidences of mortality and loss to follow-up (LTFU) were estimated using a competing risks framework.ResultsOf the 85,389 children on first-line ART, 3,555 (4%) switched to second-line after a median of 2.8 years on ART (IQR: 1.6, 4.7); 69% were from Southern Africa or SSA and 86% of second-line regimens were protease inhibitor-based. At switch, median age was 8.4 years and 50% had a prior AIDS diagnosis. Median follow-up after switch to second-line ranged from 1.8 years in SSA to 5.3 years in North America. Median CD4 counts at switch to second-line ranged from 235 cells/mm3 in SSA to 828 cells/mm3 in North America. Improvements in CD4 counts were observed over two years of follow-up, particularly in regions with lower CD4 counts at second-line switch. Improvements in weight-for-age z-scores were not observed during follow-up. Cumulative incidence of LTFU at two years was <5% in all regions except SSA (7.1%) and Southern Africa (7.4%). Risk of mortality was <3% at two years of follow-up in all regions, except Latin America (4.9%) and SSA (5.5%).ConclusionsChildren switched to second-line ART experience CD4 count increases as well as low to moderate rates of LTFU and mortality within two years after switch. Severe immune deficiency at time of switch in some settings suggests need for improved recognition and management of treatment failure in children.

Project description:BackgroundDolutegravir has been widely available in Brazil since 2017. Following the signal that infants born to women with dolutegravir exposure at conception in Botswana had a higher risk of neural tube defects (NTDs), public health leaders initiated a national investigation to evaluate periconception dolutegravir exposure among all pregnant Brazilian women with HIV and its potential association with risk of NTDs, stillbirth, or miscarriage before 22 weeks (also called spontaneous abortion).MethodsIn this retrospective, observational, national, cohort study, we identified all women with pregnancies and possible dolutegravir exposure within 8 weeks of estimated date of conception between Jan 1, 2017, and May 31, 2018, and approximately 3:1 matched pregnant women exposed to efavirenz between Jan 1, 2015, and May 31, 2018, using the Brazilian antiretroviral therapy database. We did detailed chart reviews for identified women. The primary outcomes were NTD and a composite measure of NTD, stillbirth, or miscarriage. NTD incidences were calculated with 95% CI. The composite outcome was examined with logistic regression using propensity score matching weights to balance confounders.FindingsOf 1427 included women, 382 were exposed to dolutegravir within 8 weeks of estimated date of conception. During pregnancy, 183 (48%) of 382 dolutegravir-exposed and 465 (44%) of 1045 efavirenz-exposed women received folic acid supplementation. There were 1452 birth outcomes. There were no NTDs in either dolutegravir-exposed (0, 95% CI 0-0·0010) or efavirenz-exposed groups (0, 95% CI 0-0·0036). There were 23 (6%) stillbirths or miscarriages in 384 dolutegravir-exposed fetuses and 28 (3%) in the 1068 efavirenz-exposed fetuses (p=0·0037). Logistic regression models did not consistently indicate an association between dolutegravir exposure and risk of stillbirths or miscarriages. After study closure, two confirmed NTD outcomes in fetuses with periconception dolutegravir exposure were reported to public health officials. An updated estimate of NTD incidence incorporating these cases and the estimated number of additional dolutegravir-exposed pregnancies between Jan 1, 2015 and Feb 28, 2019, is 0·0018 (95% CI 0·0005-0·0067).InterpretationNeither dolutegravir nor efavirenz exposure was associated with NTDs in our national cohort; incidence of NTDs is probably well under 1% in dolutegravir-exposed HIV-positive women but still slightly above HIV-uninfected women (0·06%) in Brazil.FundingThe Brazilian Ministry of Health and the United States' National Institutes of Health.

Project description:While efficacy data exist, there are limited data on the outcomes of patients on third-line antiretroviral therapy (ART) in sub-Saharan Africa in actual practice. Being able to identify predictors of switch to third-line ART will be essential for planning for future need. We identify predictors of switch to third-line ART among patients with significant viraemia on a protease inhibitor (PI)-based second-line ART regimen. Additionally, we describe characteristics of all patients on third-line at a large public sector HIV clinic and present their early outcomes.Retrospective analysis of adults (??18 years) on a PI-based second-line ART regimen at Themba Lethu Clinic, Johannesburg, South Africa as of 01 August 2012, when third-line treatment became available in South Africa, with significant viraemia on second-line ART (defined as at least one viral load ??1000 copies/mL on second-line ART after 01 August 2012) to identify predictors of switch to third-line (determined by genotype resistance testing). Third-line ART was defined as a regimen containing etravirine, raltegravir or ritonavir boosted darunavir, between August 2012 and January 2016. To assess predictors of switch to third-line ART we used Cox proportional hazards regression among those with significant viraemia on second-line ART after 01 August 2012. Then among all patients on third-line ART we describe viral load suppression, defined as a viral load <?400 copies/mL, after starting third-line ART.Among 719 patients in care and on second-line ART as of August 2012 (with at least one viral load ??1000 copies/mL after 01 August 2012), 36 (5.0% over a median time of 54 months) switched to third-line. Time on second-line therapy (??96 vs.?<?96 weeks) (adjusted Hazard Ratio (aHR): 2.53 95% CI 1.03-6.22) and never reaching virologic suppression while on second-line ART (aHR: 3.37 95% CI 1.47-7.73) were identified as predictors of switch. In a separate cohort of patients on third-line ART, 78.3% (47/60) and 83.3% (35/42) of those in care and with a viral load suppressed their viral load at 6 and 12 months, respectively.Our results show that the need for third-line is low (5%), but that patients' who switch to third-line ART have good early treatment outcomes and are able to suppress their viral load. Adherence counselling and resistance testing should be prioritized for patients that are at risk of failure, in particular those who never suppress on second-line and those who have been on PI-based regimen for extended periods.

Project description:To investigate the responses to switching to second-line regimens among patients who had received a long-term first-line antiretroviral therapy.Patients switching to second-line regimens from June 2008 to June 2015 were enrolled from an observational cohort. In addition, patients continuing first-line therapy and had a viral load <1000?copies/mL were included as controls in July 2012. All these patients were followed-up for 36 months or until June 2016. The virological, immunological outcomes, and drug resistance were evaluated. Virological failure was defined as viral load ?1000?copies/mL after 6 months of treatment since the start of the study.There were 304 patients switching to second-line regimens and 46 patients remaining on first-line therapy enrolled while having received first-line therapy for a median of 7.6 years. Patients with plasma viral load (VL) ?1000?copies/mL before switching to second-line regimens had a sharp decline in the proportion of virological failure with 26.7%, 20.4%, and 17.0% at 12, 24, and 36 months after regimen switch, respectively (trend test, P?<?.001). Among these patients, individuals with drug resistance (DR) had a better virological responses as compared with those without DR after regimen switching. While patients with VL <1000?copies/mL at inclusion remained a high rate of viral suppression after switching to second-line regimens. So did patients continuing first-line therapy. Among patients with VL ?1000?copies/mL before switching to second-line regimens, the rates of drug resistance were decreased from 79.4% at inclusion to 7.5% at 36 months of regimen switch, with the proportion of NRTI- and NNRTI-related drug resistance from 67.2% and 79.4% to 5.4% and 7.5%, respectively. No PI-related resistance was found. Having self-reported missing doses within a month at follow-ups were independently associated with virological failure at 36 months of switching.HIV-infected patients had viral load ?1000?copies/mL at regimen switch after a long duration of first-line therapy had good virological responses to second-line regimens, especially those harbored drug resistant variants at regimen switch. However, patients with suppressive first-line therapy did not appear to benefit virologically from switching to second-line regimens.

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.

Dataset Information

Zimbabwe's national third-line antiretroviral therapy program: Cohort description and treatment outcomes.

Publications

Zimbabwe's national third-line antiretroviral therapy program: Cohort description and treatment outcomes.

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