Alarming rates of virological failure and HIV-1 drug resistance amongst adolescents living with perinatal HIV in both urban and rural settings: evidence from the EDCTP READY-study in Cameroon

Objectives: Adolescents living with perinatal HIV infection (ALPHI) experience persistently high mortality rates, particularly in resource-limited settings. It is therefore clinically important for us to understand the therapeutic response, acquired HIV drug resistance (HIVDR) and associated factors among ALPHI, according to geographical location. Methods: A study was conducted among consenting ALPHI in two urban and two rural health facilities in the Centre Region of Cameroon. World Health Organization (WHO) clinical staging, self-reported adherence, HIVDR early warning indicators (EWIs), immunological status (CD4 count) and plasma viral load (VL) were assessed. For those experiencing virological failure (VF, VL ≥ 1000 copies/mL), HIVDR testing was performed and interpreted using the Stanford HIV Drug Resistance Database v.8.9-1. Results: Of the 270 participants, most were on nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens (61.7% urban vs. 82.2% rural), and about one-third were poorly adherent (30.1% vs. 35.1%). Clinical failure rates (WHO-stage III/IV) in both settings were < 15%. In urban settings, the immunological failure (IF) rate (CD4  < 250 cells/μL) was 15.8%, statistically associated with late adolescence, female gender and poor adherence. The VF rate was 34.2%, statistically associated with poor adherence and NNRTI-based antiretroviral therapy. In the rural context, the IF rate was 26.9% and the VF rate was 52.7%, both statistically associated with advanced clinical stages. HIVDR rate was over 90% in both settings. EWIs were delayed drug pick-up, drug stock-outs and suboptimal viral suppression. Conclusions: Poor adherence, late adolescent age, female gender and advanced clinical staging worsen IF. The VF rate is high and consistent with the presence of HIVDR in both settings, driven by poor adherence, NNRTI-based regimen and advanced clinical staging

Human Leucocyte Antigen Class I Diversity among Human Immunodeficiency Virus Exposed Negative and Positive Children in Cameroon.

The link between HLA types and HIV disease progression has been well established with alleles and residues associated to progression or non-progression to AIDS. Vertical transmission rate of HIV in Cameroon is still very high (10%). The aim of this study was to describe the diversity of HLA class I in infants born to HIV infected mothers and to determine the influence of HLA genotype in mother to child HIV transmission in Cameroon. Thirty four HIV infected infants and 28 HIV exposed but non infected infants born to HIV-positive mothers were enrolled in this study. HLA-A, HLA-B, group allele frequencies were determined by low-resolution polymerase chain reaction using sequencespecific primers. Nineteen HLA-A, 20 HLA-B allelic groups were identified in the study population. Among all the allelic variants identified, only HLA-B*44 allelic frequency resulted significantly increased in exposed non infected children (12.5% in exposed non infected versus 2.9% in exposed HIV-infected children, p=0.04). HLA-B*44 may be associated with the resistance to HIV infection upon mother to child exposure

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

BackgroundWith 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.MethodsAn 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; <20: susceptible). The acceptable threshold for potential-efficacy was set at 80%.ResultsThe median [IQR] CD4, viral RNA, and time on ART, were respectively 129 [29-466] cells/l, 71,630 [19,041-368,000] copies/ml, and 4 [2-5] years. Overall HIVDR-level was 89.11% (90/101), with 83.2% harbouring M184V (high-level 3TC/FTC-resistance) and only 1.98% (2/101) major HIVDR-mutations to ritonavir-boosted protease-inhibitors (PI/r). Thymidine-analogue mutations (TAMs)-1 [T215FY (46.53%), M41L (22.77%), L210W (8.91%)], with cross-resistance to AZT and TDF, were higher compared to TAMs-2 [D67N (21.78%), K70R (19.80%), K219QE (18.81%)]. As expected, K65R was related with TDF-exposure: 0% (0/55) in group-A, 22.72% (5/22) group-B, 4.17% (1/24) group-C (p=0.0013). The potential-efficacy of AZT vs. TDF was respectively 43.64% (24/55) vs. 70.91% (39/55) in group-A (p=0.0038); 63.64% (14/22) vs. 68.28% (15/22) in group-B (p=1.0000); and 37.50% (9/24) vs. 83.33% (20/24) in group-C (p=0.0032). CRF02_AG was the prevailing subtype (63.40%), followed by CRF11.cpx (8.91%), A(1) (7.92%), G (5.94%); without any significant effect of the subtype-distribution on HIVDR (92.2% in CRF02_AG vs. 83.8% in non-AG; p=0.204).ConclusionFirst-line ART-failure exhibits high-level NRTI-resistance, with potential lower-efficacy of AZT compared to TDF. Significantly, using our 80% efficacy-threshold, only patients without NRTI-substitution on first-line could effectively switch to SLC following the WHO-approach. Patients with multiple NRTI-substitutions (exposed to both thymidine-analogues and TDF) on first-line ART would require HIVDR-testing to select active NRTIs for SLC