Xpert HIV-1 qual point-of-care testing for HIV early infant diagnosis in Tanzania: experiences and perceptions of health care workers in a 2016 study.

BACKGROUND: HIV early infant diagnosis (HEID) at the centralized laboratory faces many challenges that impact the cascade of timely HEID. Point of Care (PoC) HEID has shown to reduce test turnaround times, allow for task shifting and has the potential to reduce infant mortality. We aimed at assessing the feasibility of nurse based PoC-HEID in five facilities of Mbeya region. METHODS: We analysed data from healthcare workers at five obstetric health facilities that participated in the BABY study which enrolled mothers living with HIV and their HIV exposed infants who were followed up until 6 weeks post-delivery. Nurses and laboratory personnel were trained and performed HEID procedures using the Xpert HIV-1 Qual PoC systems. Involved personnel were interviewed on feasibility, knowledge and competency of procedures and overall impression of the use of HIV-1 Qual PoC system in clinical settings. RESULTS: A total of 28 health care workers (HCWs) who participated in the study between 2014 and 2016 were interviewed, 23 being nurses, 1 clinical officer, 1 lab scientist and 3 lab technicians The median age was 39.5 years. Majority of the nurses (22/24) and all lab staff were confident using Gene Xpert PoC test after being trained. None of them rated Gene Xpert handling as too complicated despite minor challenges. Five HCWs (5/24) reported power cut as the most often occurring problem. As an overall impression, all interviewees agreed on PoC HEID to be used in clinical settings however, about half of them (11/24) indicated that the PoC-HEID procedures add a burden onto their routine workload. CONCLUSION: Overall, health care workers in our study demonstrated very good perceptions and experiences of using PoC HEID. Efforts should be invested on quality training, targeted task distribution at the clinics, continual supportive supervision and power back up mechanisms to make the wide-scale adoption of nurse based PoC HEID testing a possibility.

Long-term follow-up on HIV infected and non-infected women with cervical cancer from Tanzania: staging, access to cancer-directed therapies and associated survival in a real-life remote setting.

BACKGROUND: Worldwide 85% of cervical cancer (CC) related deaths occur in low- and middle-income countries. Sub-Saharan Africa is burdend by an overlapping high incidence of CC as well as HIV infection, a risk factor for HPV associated disease progression. Recent upscaling of CC screening activities increased the number of CC diagnoses in a previous unscreened population. The aim of the 2H study was to follow up on women with CC in the context of available health care services in Tanzania in relation to their HIV infection status. METHODS: This longitudinal observational cohort study included women with histological confirmed CC from Mbeya, Tanzania, between 2013-2019. All women were referred for CC staging and cancer-directed therapies (CDT), including surgery and/or radio-chemotherapy, or palliative care. Annual follow-up focused on successful linkage to CDT, interventions and survival. We assessed factors on compliance, used Kaplan-Meier-Survivor functions to evaluate survival time and poisson regression models to calculate incidence rate ratios on mortality (IRR) two years after diagnosis. RESULTS: Overall, 270 women with CC (123 HIV infected) were included. Staging information, available in 185 cases, showed 84.9% presented with advanced stage disease (FIGO ≥ IIB), no difference was seen in respect to HIV status. HIV-infected women were 12 years younger at the time of cancer diagnosis (median age 44.8 versus 56.4 years, p < 0.001). Median follow up period was 11.9 months (range 0.2-67.2). Survival information, available in 231 cases, demonstrated for women diagnosed in early-stage disease a median survival time of 38.3 months, in advanced-stage 16.0 months and late-stage disease 6.5 months after diagnosis. Of all women, 42% received CDT or palliative support. HIV co-infection and education were associated with higher health care compliance. CDT was significantly associated with lower 2-year mortality rates (IRR 0.62, p = 0.004). HIV coinfection did not impact mortality rates after diagnosis. CONCLUSION: High numbers of advanced and late staged CC were diagnosed, compliance to CDT was low. A beneficial impact of CDT on CC mortality could be demonstrated for local health care services. This study indicates challenges for successful linkage and supports an effective scale up of cancer care and treatment facilities.

Depression management and antiretroviral treatment outcome among people living with HIV in Northwest and East regions of Cameroon.

BACKGROUND: Several interventions have shown benefits in improving mental health problems such as depression which is common in people living with HIV. However, there is a paucity of evidence on the effect of these interventions in improving HIV treatment outcomes. This study aimed at bridging this evidence gap and guiding the integration of depression and HIV management, particularly in rural health settings of Cameroon. MATERIALS AND METHODS: We carried out a cluster-randomized intervention study targeting persons aged 13 years and above who had been on antiretroviral treatment for 6-9 months. Participants were followed up for 12 months during which those in the intervention group underwent routine screening and management of depression. Comparisons were done using the two-way ANOVA and Chi-squared test with significance set at 5%. RESULTS: Overall, 370 participants with a median age of 39 years (IQR: 30-49) were enrolled in this study. Of these, 42 (11.3%) were screened with moderate to severe depressive symptoms and 41 (11.1%) had poor treatment adherence. There was a significant drop in depression scores in the intervention group from 3.88 (± 3.76) to 2.29 (± 2.39) versus 4.35 (± 4.64) to 3.39 (± 3.0) in controls (p < 0.001) which was accompanied by a drop in the prevalence of moderate to severe depressive symptoms in the intervention group from 9% to 0.8% (p = 0.046). Decreased depression scores were correlated with better adherence scores with correlation coefficients of - 0.191, - 0.555, and - 0.513 at baseline, 6 months, and 12 months of follow-up respectively (p < 0.001) but there was no significant difference in adherence levels (p = 0.255) and viral suppression rates (p = 0.811) between groups. CONCLUSION: The results of this study suggest that considering routine screening and management of depression as an integral component of HIV care could positively impact HIV treatment outcomes. However, there is a need for more research to identify the best combinations of context-specific and cost-effective strategies that can impactfully be integrated with HIV management. Trial registration Trial registration Number: DRKS00027440. Name of Registry: German Clinical Trials Register. Date registration: December 10, 2021 ('retrospectively registered'). Date of enrolment of the first participant: 05/08/2019.

High turnaround times and low viral resuppression rates after reinforced adherence counselling following a confirmed virological failure diagnostic algorithm in HIV-infected patients on first-line antiretroviral therapy from Tanzania.

OBJECTIVE: Early identification of confirmed virological failure is paramount to avoid accumulation of drug resistance in patients on antiretroviral therapy (ART). Scale-up of HIV-RNA monitoring in Africa and timely switch to second-line regimens are challenged. METHODS: A WHO adapted confirmed virological treatment screening algorithm (HIV-RNA screening, enhanced adherence counselling, confirmatory HIV-RNA testing) was evaluated in HIV-infected patients on first-line ART from Tanzania. The main endpoints included viral resuppression and virological failure rates, retention and turnaround time of the screening algorithm until second-line ART initiation. Secondary endpoints included risk factors for virological treatment failure and patterns of genotypic drug resistance. RESULTS: HIV-RNA >1000 copies/ml at first screening was detected in 58/356 (16.3%) patients (median time-on-treatment 6.3 years, 25% immunological treatment failure). Adjusted risk factors for virological failure were age <30 years (RR 5.2 [95% CI: 2.5-10.8]), years on ART ≥3 years (RR 3.0 [1.0-8.9]), CD4-counts <200 cells/µl (RR 9.3 [4.0-21.8]) and poor self-reported treatment adherence (RR 2.0 [1.2-3.4]). Resuppression of HIV-RNA <1000 copies/ml was observed in 5/50 (10%) cases after enhanced adherence counselling. Confirmatory testing within 3 months was performed in only 46.6% and switch to second-line ART within 6 months in 60.4% of patients. Major NNRTI-mutation were detected in all of 30 patients, NRTI mutations in 96.7% and ≥3 thymidine-analogue mutations in 40%. No remaining NRTI options were predicted in 57% and limited susceptibility in 23% of patients. CONCLUSION: We observed low levels of viral resuppression following adherence counselling, associated with high levels of accumulated drug resistance. High visit burden and turnaround times for confirmed virological failure diagnosis further delayed switching to second-line treatment which could be improved using novel point-of-care viral load monitoring systems.

OBJECTIF: L'identification précoce de l'échec virologique confirmé est primordiale pour éviter l'accumulation de résistance aux médicaments chez les patients sous traitement antirétroviral (ART). L'intensification du suivi de l'ARN du VIH en Afrique et le passage en temps opportun aux schémas thérapeutiques de deuxième intention sont adressés. MÉTHODES: Nous avons évalué un algorithme adapté de l'OMS confirmé pour le dépistage du traitement virologique (dépistage de l'ARN du VIH, adhésion renforcée du conseil, test de confirmation de l'ARN du VIH) chez des patients infectés par le VIH sous ART de première intention en Tanzanie. Les critères principaux comprenaient la répression virale et les taux d'échec virologique, la rétention et et la durée de rotation de l'algorithme de dépistage jusqu'à l'initiation de l'ART de deuxième ligne. Les critères d'évaluation secondaires comprenaient les facteurs de risque d'échec du traitement virologique et les profils de résistance génotypique aux médicaments. RÉSULTATS: Un ARN-VIH >1000 copies/ml au premier dépistage a été détecté chez 58/356 (16,3%) patients (durée médiane de traitement de 6,3 ans, 25% d'échec immunologique du traitement). Les facteurs de risque ajustés pour l'échec virologique étaient l'âge <30 ans (RR: 5,2 [IC95%: 2,5-10,8]), les années sous ART ≥3 ans (RR: 3,0 [1,0-8,9]), la numération des CD4 <200 cellules/µL (RR: 9,3 [4,0-21,8]) et une mauvaise compliance au traitement autodéclarée (RR: 2,0 [1,2-3,4]). Une re-suppression du VIH-ARN <1000 copies/mL a été observée chez 5/50 (10%) des cas après renforcement du conseil pour la compliance. Un test de confirmation dans les 3 mois n'a été réalisé que dans 46,6% des cas et le passage à l'ART de deuxième ligne dans les 6 mois chez 60,4% des patients. Des mutations NNRTI majeures ont été détectées chez tous les 30 patients, des mutations NRTI chez 96,7% et ≥3 mutations analogues à la thymidine chez 40%. Aucune option NRTI restante n'a été prévue chez 57% des cas et une sensibilité limitée chez 23% des patients. CONCLUSION: Nous avons observé de faibles taux de re-suppression virale après des conseils d'adhésion, associés à des taux élevés de résistance accumulée aux médicaments. La charge élevée des visites et les délais de rotation pour le diagnostic confirmé d'échec virologique ont retardé le passage au traitement de deuxième intention, ce qui pourrait être amélioré à l'aide de nouveaux systèmes de surveillance de la charge virale au point des soins.

Accuracy and Operational Characteristics of Xpert Human Immunodeficiency Virus Point-of-Care Testing at Birth and Until Week 6 in Human Immunodeficiency Virus-exposed Neonates in Tanzania.

Background: Point-of-care (PoC) systems for early infant diagnosis (EID) may improve timely infant human immunodeficiency virus (HIV) management. Experiences within African public health settings are limited. Methods: We evaluated the accuracy and operational feasibility of the Xpert HIV-1 Qual for PoC-EID testing, using fresh blood and dried blood spots (DBS) samples at obstetric health facilities in Tanzania at birth and at postpartum weeks 1, 2, 3, and 6 in HIV-exposed infants. Test results were confirmed using TaqMan DBS HIV-deoxyribonucleic acid and/or plasma HIV-ribonucleic acid (RNA) testing. Results: At week 6, 15 (2.5%) out of 614 infants were diagnosed with HIV; 10 (66.7%) of them at birth (median HIV-RNA 4570 copies/mL). At birth, the Xpert-PoC and Xpert-DBS were 100% sensitive (95% confidence intervals: PoC, 69.2-100%; DBS, 66.4-100%) and 100% specific (PoC, 92.1-100%; DBS, 88.4-100%). By week 3, 5 infants with intra/postpartum HIV-infection (median HIV-RNA 1 160 000 copies/mL) were all correctly diagnosed by Xpert. In 2 cases, Xpert-PoC testing correctly identified HIV-infection when DBS tests (Xpert and TaqMan) were negative, suggesting a greater sensitivity. In 2 infants with confirmed HIV at birth, all tests were negative at week 6, possibly because of viral suppression under nevirapine prophylaxis. Problems were reported in 183/2736 (6.7%) of Xpert-PoC tests, mostly related to power cuts (57.9%). Conclusions: We demonstrated excellent Xpert HIV-1 Qual performance and good operational feasibility for PoC-EID testing at obstetric health facilities. Week 6 sensitivity issues were possibly related to nevirapine prophylaxis, supporting additional birth PoC-EID testing to avoid underdiagnosis. Clinical Trials Registration: NCT02545296.

Preferential Targeting of Conserved Gag Regions after Vaccination with a Heterologous DNA Prime-Modified Vaccinia Virus Ankara Boost HIV-1 Vaccine Regimen.

Prime-boost vaccination strategies against HIV-1 often include multiple variants for a given immunogen for better coverage of the extensive viral diversity. To study the immunologic effects of this approach, we characterized breadth, phenotype, function, and specificity of Gag-specific T cells induced by a DNA-prime modified vaccinia virus Ankara (MVA)-boost vaccination strategy, which uses mismatched Gag immunogens in the TamoVac 01 phase IIa trial. Healthy Tanzanian volunteers received three injections of the DNA-SMI vaccine encoding a subtype B and AB-recombinant Gagp37 and two vaccinations with MVA-CMDR encoding subtype A Gagp55 Gag-specific T-cell responses were studied in 42 vaccinees using fresh peripheral blood mononuclear cells. After the first MVA-CMDR boost, vaccine-induced gamma interferon-positive (IFN-γ+) Gag-specific T-cell responses were dominated by CD4+ T cells (P < 0.001 compared to CD8+ T cells) that coexpressed interleukin-2 (IL-2) (66.4%) and/or tumor necrosis factor alpha (TNF-α) (63.7%). A median of 3 antigenic regions were targeted with a higher-magnitude median response to Gagp24 regions, more conserved between prime and boost, compared to those of regions within Gagp15 (not primed) and Gagp17 (less conserved; P < 0.0001 for both). Four regions within Gagp24 each were targeted by 45% to 74% of vaccinees upon restimulation with DNA-SMI-Gag matched peptides. The response rate to individual antigenic regions correlated with the sequence homology between the MVA- and DNA Gag-encoded immunogens (P = 0.04, r2 = 0.47). In summary, after the first MVA-CMDR boost, the sequence-mismatched DNA-prime MVA-boost vaccine strategy induced a Gag-specific T-cell response that was dominated by polyfunctional CD4+ T cells and that targeted multiple antigenic regions within the conserved Gagp24 protein.IMPORTANCE Genetic diversity is a major challenge for the design of vaccines against variable viruses. While including multiple variants for a given immunogen in prime-boost vaccination strategies is one approach that aims to improve coverage for global virus variants, the immunologic consequences of this strategy have been poorly defined so far. It is unclear whether inclusion of multiple variants in prime-boost vaccination strategies improves recognition of variant viruses by T cells and by which mechanisms this would be achieved, either by improved cross-recognition of multiple variants for a given antigenic region or through preferential targeting of antigenic regions more conserved between prime and boost. Engineering vaccines to induce adaptive immune responses that preferentially target conserved antigenic regions of viral vulnerability might facilitate better immune control after preventive and therapeutic vaccination for HIV and for other variable viruses.

Using a composite adherence tool to assess ART response and risk factors of poor adherence in pregnant and breastfeeding HIV-positive Cameroonian women at 6 and 12 months after initiating option B.

BACKGROUND: Antiretroviral therapy (ART) adherence in preventing HIV mother-to-child transmission in association with virological suppression and risk factors of low adherence in the Cameroon's Option B+ programme are poorly understood. We used a composite adherence score (CAS) to determine adherence and risk factors of poor adherence in association with virological treatment response in HIV-positive pregnant and breastfeeding women who remained in care at 6 and 12 months after initiating ART. METHODS: We prospectively enrolled 268 women after ART initiation between October 2013 and December 2015 from five facilities within the Kumba health district. Adherence at 6 and 12 months were measured using a CAS comprising of a 6-month medication refill record review, a four-item self-reported questionnaires and a 30-day visual analogue scale. Adherence was defined as the sum scores of the three measures and classified as high, moderate and low. Measured adherence levels were compared to virological suppression rates at month 12 and risk factors of poor adherence were determined. RESULTS: At 6 and 12 months, 217 (81.0%) and 185 (69.0%) women were available for adherence evaluation. Respectively. Of those, 128 (59.0%) and 68 (31.4%) had high or moderate adherence as per the CAS tool at month 6, and 116 (62.7%) and 48 (24.9%) at month 12, respectively. Viral loads were assessed in 165 women at months 12, and 92.7% had viral suppression (< 1000 copies/mL). Viral suppression was seen in 100% of women with high, 89.5% with moderate, and 52.9% with low adherence using the CAS tool. Virological treatment failure was significantly associated with low adherence [OR 7.6, (95%CI, 1.8-30.8)]. Risk factors for low adherence were younger age [aOR 3.8, (95%CI, 1.4-10.6)], primary as compared to higher levels of education [aOR 2.7, (95%CI, 1.4-5.2)] and employment in the informal sector compared to unemployment [aOR 1.9, (95%CI,1.0-3.6)]. CONCLUSIONS: During the first year of Option B+ implementation in Cameroon our novel CAS adherence tool was feasible, and useful to discriminate ART adherence levels which correlated with viral suppression. Younger age, less educated and informal sector employed women may need more attention for optimal adherence to reduce the risk of virological failure.

Safety and Immunogenicity of PENNVAX-G DNA Prime Administered by Biojector 2000 or CELLECTRA Electroporation Device With Modified Vaccinia Ankara-CMDR Boost.

Background: We report the first-in-human safety and immunogenicity evaluation of PENNVAX-G DNA/modified vaccinia Ankara-Chiang Mai double recombinant (MVA-CMDR) prime-boost human immuonodeficiency virus (HIV) vaccine, with intramuscular DNA delivery by either Biojector 2000 needle-free injection system (Biojector) or CELLECTRA electroporation device. Methods: Healthy, HIV-uninfected adults were randomized to receive 4 mg of PENNVAX-G DNA delivered intramuscularly by Biojector or electroporation at baseline and week 4 followed by intramuscular injection of 108 plaque forming units of MVA-CMDR at weeks 12 and 24. The open-label part A was conducted in the United States, followed by a double-blind, placebo-controlled part B in East Africa. Solicited and unsolicited adverse events were recorded, and immune responses were measured. Results: Eighty-eight of 100 enrolled participants completed all study injections, which were generally safe and well tolerated, with more immediate, but transient, pain in the electroporation group. Cellular responses were observed in 57% of vaccine recipients tested and were CD4 predominant. High rates of binding antibody responses to CRF01_AE antigens, including gp70 V1V2 scaffold, were observed. Neutralizing antibodies were detected in a peripheral blood mononuclear cell assay, and moderate antibody-dependent, cell-mediated cytotoxicity activity was demonstrated. Discussion: The PVG/MVA-CMDR HIV-1 vaccine regimen is safe and immunogenic. Substantial differences in safety or immunogenicity between modes of DNA delivery were not observed. Clinical Trials Registration: NCT01260727.

Uptake and performance of prevention of mother-to-child transmission and early infant diagnosis in pregnant HIV-infected women and their exposed infants at seven health centres in Addis Ababa, Ethiopia.

OBJECTIVE: To assess the uptake of WHO-recommended PMTCT procedures in Ethiopia's health services. METHODS: Prospective observational study of HIV-positive pregnant mothers and their newborns attending PMTCT services at seven health centres in Addis Ababa. Women were recruited during antenatal care and followed up with their newborns at delivery, Day 6 and Week 6 post-partum. Retention to PMCTC procedures, self-reported antiretroviral treatment (ART) adherence and HIV infant outcome were assessed. Turnaround times of HIV early infant diagnosis (EID) procedures were extracted from health registers. RESULTS: Of 494 women enrolled, 4.9% did not complete PMTCT procedures due to active denial or loss to follow-up. HIV was first diagnosed in 223 (45.1%) and ART initiated in 321 (65.0%) women during pregnancy. ART was initiated in a median of 1.3 weeks (IQR 0-4.3) after HIV diagnosis. Poor self-reported treatment adherence was higher post-partum than during pregnancy (12.5% vs. 7.0%, P = 0.002) and significantly associated with divorced/separated marital status (RR 2.2, 95% CI 1.3-3.8), low family income (RR 2.1, 95% CI 1.1-4.1), low CD4 count (RR 1.7, 95% CI 1.0-3.0) and ART initiation during delivery (RR 2.5, 95% CI 1.1-5.6). Of 435 infants born alive, 98.6% received nevirapine prophylaxis. The mother-to-child HIV transmission rate was 0.7% after a median of 6.7 weeks (IQR 6.4-10.4), but EID results were received for only 46.6% within 3 months of birth. CONCLUSION: High retention in PMTCT services, triple maternal ART and high infant nevirapine prophylaxis coverage were associated with low mother-to-child HIV transmission. Declining post-partum ART adherence and challenges of EID linkage require attention.

Retention in care and reasons for discontinuation of lifelong antiretroviral therapy in a cohort of Cameroonian pregnant and breastfeeding HIV-positive women initiating 'Option B+' in the South West Region.

OBJECTIVE: To assess linkage and retention in care along the PMTCT cascade in HIV-positive pregnant and breastfeeding women initiating Option B+ in Cameroon. METHODS: We prospectively determined uptake of HIV testing and counselling (HTC), uptake of ART and retention in care after Option B+ initiation between October 2013 and December 2014 in pregnant and breastfeeding women from five sites within the Kumba Health District. Retention in care was assessed over at least 12 months follow-up and estimated by Kaplan-Meier analysis. During follow-up, tracing outcomes and reasons for discontinuing treatment were documented. RESULTS: The uptake of HTC of 5813 women with unknown HIV status was 98.5%, 251 (4.4%) were newly diagnosed HIV positive, and ART uptake in women eligible to start Option B+ was 96.8%. We enrolled 268 women initiating lifelong ART in the follow-up. Overall, 65 (24.3%) discontinued treatment, either defined by loss to follow-up (44.6%) or actively stopped treatment (55.8%). Retention in care was 88.0% and 81.1% at 6 and 12 months, respectively. Discontinuation was significantly associated in multivariate analysis with small sites and high staff turnover [aOR 2.5 (95% CI 1.6, 3.9), P < 0.001]. Main reasons for stopping treatment were HIV status denial and stigma (52.8%), religious reasons (25.0%) and lack of transport fare (11.1%). CONCLUSION: We observed good uptake of HTC, ART and retention in care, which declined over time. Discontinuation of Option B+ was highest at small sites with a high staff turnover. Improved staffing, adequate task shifting and community interventions to track defaulters including reducing stigma and religious beliefs may improve Option B+ retention.