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HIV-1 drug resistance testing is essential for heavily-treated patients switching from first- to second-line regimens in resource-limited settings: evidence from routine clinical practice in Cameroon.

ABSTRACT: BACKGROUND:With the phase-out of stavudine (d4T), change to first-line regimens with zidovudine (AZT) or tenofovir (TDF) in resource-limited settings (RLS) might increase risks of cross-resistance to nucleos(t) ide reverse transcriptase inhibitors (NRTI). This would restrict the scope of switching to the World Health Organisation (WHO)-recommended standard second-line combinations (SLC) without HIV drug resistance (HIVDR)-testing in routine clinical practice. METHODS:An observational study was conducted among 101 Cameroonian patients (55.4% male, median [IQR] age 34 [10-41] years) failing first-line antiretroviral therapy (ART) in 2016, and stratified into three groups according to NRTIs exposure: exposure to both thymidine analogues AZT "and" D4T (group-A, n =?55); exposure to both TDF and AZT "or" D4T (group-B, n =?22); exposure solely to D4T (group-C, n =?24). Protease-reverse transcriptase HIVDR was interpreted using the HIVdb penalty scores (?60: high-resistance; 20-59: intermediate-resistance;

SUBMITTER: Takou D

PROVIDER: S-EPMC6419466 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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HIV-1 drug resistance testing is essential for heavily-treated patients switching from first- to second-line regimens in resource-limited settings: evidence from routine clinical practice in Cameroon.

Takou Desire D Fokam Joseph J Teto Georges G Santoro Maria-Mercedes MM Ceccherini-Silberstein Francesca F Nanfack Aubin Joseph AJ Sosso Samuel Martin SM Dambaya Béatrice B Salpini Romina R Billong Serge Clotaire SC Gori Caterina C Fokunang Charles Ntungwen CN Cappelli Giulia G Colizzi Vittorio V Perno Carlo-Federico CF Ndjolo Alexis A

BMC infectious diseases 20190312 1

<h4>Background</h4>With the phase-out of stavudine (d4T), change to first-line regimens with zidovudine (AZT) or tenofovir (TDF) in resource-limited settings (RLS) might increase risks of cross-resistance to nucleos(t) ide reverse transcriptase inhibitors (NRTI). This would restrict the scope of switching to the World Health Organisation (WHO)-recommended standard second-line combinations (SLC) without HIV drug resistance (HIVDR)-testing in routine clinical practice.<h4>Methods</h4>An observatio ...[more]

PMID: 30871487

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Project description:IntroductionIn 2007, the Cameroon Baptist Convention Health Services (CBCHS) initiated an assisted partner notification services (aPNS) public health programme to increase HIV case identification and reduce HIV incidence in the most affected regions of Cameroon. We describe large-scale implementation of aPNS and overall programmatic achievements in a resource-limited setting through 2015.MethodsCBCHS trained health advisors (HAs) from 16 CBCHS facilities and 22 non-CBCHS facilities to integrate aPNS into their existing jobs in five of the ten Cameroon regions. HAs recorded basic demographic, clinical and risk factor information from consenting index persons (IPs) and similar information about their sexual partners'/contact persons (CPs) on interview records and aPNS registers. These data were entered into an Epi-Info database. HAs provided pre-test counselling to CPs and offered them HIV testing in their home or other location. HAs educated IPs and CPs on HIV prevention and risk reduction, and referred IPs and HIV positive CPs to HIV care and treatment centres. Starting in 2014, HAs re-interviewed IPs 30 days after their initial aPNS interview to ascertain instances of social harms following partner notification. Continuous predictor and outcome variables were summarized using median and interquartile range, while categorical variables were summarized using percentages from 2007 to 2015.ResultsA total of 18,730 IPs (71% women) received aPNS over nine years. IPs identified 21,057 CPs (67% men) (mean CP/IP 1.12), of whom 12,867 (61.1%) were notified of their exposure to HIV. A total of 9202 (71.5% of notified CPs) tested for HIV, 4764 (51.8%) of whom tested HIV positive (number of IPs needed to interview = 3.9); 3112 (65.3%) HIV-positive partners were referred to HIV care and treatment centres. Of the 976 IPs receiving aPNS in 2014 to 2015, for whom follow-up data were available, 11 (1.1%) reported physical intimate partner violence from CPs. Thus, 44.3% of 1224 CPs were notified through provider referral. Of the 784 CPs who tested for HIV, 157 were newly diagnosed and the overall HIV prevalence was 41.6% (326/784).ConclusionsaPNS is feasible, can be brought to scale, yields a high level of case identification, and is infrequently associated with social harms and intimate partner violence.

Project description:BackgroundEarly infant diagnosis (EID) of HIV is a key-point for the implementation of early HAART, associated with lower mortality in HIV-infected infants. We evaluated the EID process of HIV according to national recommendations, in urban areas of Cameroon.Methods/findingsThe ANRS12140-PEDIACAM study is a multisite cohort in which infants born to HIV-infected mothers were included before the 8(th) day of life and followed. Collection of samples for HIV DNA/RNA-PCR was planned at 6 weeks together with routine vaccination. The HIV test result was expected to be available at 10 weeks. A positive or indeterminate test result was confirmed by a second test on a different sample. Systematic HAART was offered to HIV-infected infants identified. The EID process was considered complete if infants were tested and HIV results provided to mothers/family before 7 months of age. During 2007-2009, 1587 mother-infant pairs were included in three referral hospitals; most infants (n?=?1423, 89.7%) were tested for HIV, at a median age of 1.5 months (IQR, 1.4-1.6). Among them, 51 (3.6%) were HIV-infected. Overall, 1331 (83.9%) completed the process by returning for the result before 7 months (median age: 2.5 months (IQR, 2.4-3.0)). Incomplete process, that is test not performed, or result of test not provided or provided late to the family, was independently associated with late HIV diagnosis during pregnancy (adjusted odds ratio (aOR)?=?1.8, 95%CI: 1.1 to 2.9, p?=?0.01), absence of PMTCT prophylaxis (aOR?=?2.4, 95%CI: 1.4 to 4.3, p?=?0.002), and emergency caesarean section (aOR?=?2.5, 95%CI: 1.5 to 4.3, p?=?0.001).ConclusionsIn urban areas of Cameroon, HIV-infected women diagnosed sufficiently early during pregnancy opt to benefit from EID whatever their socio-economic, marital or disclosure status. Reduction of non optimal diagnosis process should focus on women with late HIV diagnosis during pregnancy especially if they did not receive any PMTCT, or if complications occurred at delivery.

Project description:Objective:The use of some antiretroviral drugs has been associated with a higher risk of diabetes mellitus (DM) in HIV-infected patients, but the risk associated with antiretroviral drug combinations remains unclear. We investigated the association between first-line antiretroviral therapy (ART) regimens, recommended by the World Health Organization (WHO) in 2016, and the risk of DM in adults. Method:We selected all HIV-infected adults within the Thai National AIDS Program who started a first-line ART regimen consisting the following between October 2006 and September 2013: zidovudine+lamivudine+nevirapine; tenofovir disoproxil fumarate (TDF)+lamivudine+nevirapine; zidovudine+lamivudine+efavirenz; TDF+lamivudine/emtricitabine+efavirenz; zidovudine+lamivudine+ritonavir-boosted lopinavir (LPV/r); or TDF+lamivudine+LPV/r. Diagnosis of DM was defined as having at least 2 of the following characteristics: fasting plasma glucose ?126 mg/dl, 2010 WHO ICD-10 codes E11-E14, or prescription of antidiabetic drugs. To identify ART regimens associated with DM, we used competing risks regression models that considered mortality without DM as a competing event and adjusted for sex, age, pancreas disease, and stratified by groups defined by a score summarizing the propensity to receive a specific first-line ART regimen. Results:Data from 35 710 adults (49.1% male; median age, 35.0 years; median follow-up, 2.0 years) were included. In the multivariable analysis with zidovudine+lamivudine+nevirapine as the reference group, a higher risk of DM was observed with TDF+lamivudine/emtricitabine+efavirenz (adjusted sub-distribution hazard ratio [aSHR], 1.6; 95% confidence interval [CI], 1.3-1.9), zidovudine+lamivudine+efavirenz (aSHR, 2.0; 95% CI, 1.7-2.3), and TDF+lamivudine+LPV/r (aSHR, 2.7; 95% CI, 1.9-3.9). Conclusions:Several of the WHO recommended ART regimens, particularly tenofovir + lamivudine +LPV/r and regimens containing efavirenz, may be associated with an increased risk of DM.

Dataset Information

HIV-1 drug resistance testing is essential for heavily-treated patients switching from first- to second-line regimens in resource-limited settings: evidence from routine clinical practice in Cameroon.

Publications

HIV-1 drug resistance testing is essential for heavily-treated patients switching from first- to second-line regimens in resource-limited settings: evidence from routine clinical practice in Cameroon.

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