Continuum of HIV Care in Rural Mozambique: The Implications of HIV Testing Modality on Linkage and Retention

INTRODUCTION: Context-specific improvements in the continuum of HIV care are needed in order to achieve the UNAIDS target of 90-90-90. This study aimed to assess the linkage to and retention in HIV care according to different testing modalities in rural southern Mozambique. METHODS: Adults newly diagnosed with HIV from voluntary counseling and testing (VCT), provider-initiated (PICT) and home-based HIV testing (HBT) services were prospectively enrolled between 2014- 2015 at the Manhica District. Patients were passively followed-up through chart examination .Tracing was performed at 12-months to ascertain causes of loss to follow-up. Fine and Grey competing risk analysis was performed to determine factors associated with the each step of the cascade. RESULTS: Overall linkage to care as defined by having a CD4 count at 3 months, was 43.7% (95CI% 40.8-46.6) and 25.2% of all participants initiated ART. Factors associated with increased linkage in multivariable analysis included testing at VCT, older age, having been previously tested for HIV, owning a cell phone, presenting with WHO clinical stages III/IV, self-reported illness-associated disability in the previous month , and later calendar month of participant recruitment. Ascertaining deaths and transfers allowed adjustment of the rate of 12-month retention in treatment from 75.6% (95% CI 70.2-80.5) to 84.2% (95% CI 79.2-88.5). CONCLUSIONS: HBT reached a socio-demographically distinct population from that of clinic based testing modalities but low linkage to care points to a need for facilitated linkage interventions. Distinguishing between true treatment defaulting and other causes of loss-to-follow-up can significantly change indicators of retention in care

Reengagement of HIV-infected children lost to follow-up after active mobile phone tracing in a rural area of Mozambique

Introduction: Retention in care and reengagement of lost to follow-up (LTFU) patients are priority challenges in pediatric HIV care. We aimed to assess whether a telephone-call active tracing program facilitated reengagement in care (RIC) in the Manhiça District Hospital, Mozambique. Methods: Telephone tracing of LTFU children was performed from July 2016 to March 2017. Both ART (antiretroviral treatment) and preART patients were included in this study. LTFU was defined as not attending the clinic for ≥120 days after last attended visit. Reengagement was determined 3 months after an attempt to contact. Results: A total of 144 children initially identified as LTFU entered the active tracing program and 37 were reached by means of telephone tracing. RIC was 57% (95% CI, 39–72%) among children who could be reached versus 18% (95% CI, 11–26%) of those who could not be reached (p = 0.001). Conclusion: Telephone tracing could be an effective tool for facilitating reengagement in pediatric HIV care. However, the difficulty of reaching patients is an obstacle that can undermine the program

Loss to follow-up and opportunities for reengagement in HIV care in rural Mozambique: A prospective cohort study.

"Patients lost to follow-up (LTFU) over the human immunodeficiency virus (HIV) cascade have poor clinical outcomes and contribute to onward HIV transmission. We assessed true care outcomes and factors associated with successful reengagement in patients LTFU in southern Mozambique.Newly diagnosed HIV-positive adults were consecutively recruited in the Manhi\xC3\xA7a District. Patients LTFU within 12 months after HIV diagnosis were visited at home from June 2015 to July 2016 and interviewed for ascertainment of outcomes and reasons for LTFU. Factors associated with reengagement in care within 90 days after the home visit were analyzed by Cox proportional hazards model.Among 1122 newly HIV-diagnosed adults, 691 (61.6%) were identified as LTFU. Of those, 557 (80.6%) were approached at their homes and 321 (57.6%) found at home. Over 50% had died or migrated, 10% had been misclassified as LTFU, and 252 (78.5%) were interviewed. Following the visit, 79 (31.3%) reengaged in care. Having registered in care and a shorter time between LTFU and visit were associated with reengagement in multivariate analyses: adjusted hazards ratio of 3.54 [95% confidence interval (CI): 1.81-6.92; P\xE2\x80\x8A<\xE2\x80\x8A.001] and 0.93 (95% CI: 0.87-1.00; P\xE2\x80\x8A=\xE2\x80\x8A.045), respectively. The most frequently reported barriers were the lack of trust in the HIV-diagnosis, the perception of being in good health, and fear of being badly treated by health personnel and differed by type of LTFU.Estimates of LTFU in rural areas of sub-Saharan Africa are likely to be overestimated in the absence of active tracing strategies. Home visits are resource-intensive but useful strategies for reengagement for at least one-third of LTFU patients when applied in the context of differentiated care for those LTFU individuals who had already enrolled in HIV care at some point.

Tipping the balance towards long-term retention in the HIV care cascade: A mixed methods study in southern Mozambique

BACKGROUND: The implementation of quality HIV control programs is crucial for the achievement of the UNAIDS 90-90-90 targets and to motivate people living with HIV (PLWHIV) to link and remain in HIV-care. The aim of this mixed method cross-sectional study was to estimate the linkage and long-term retention in care of PLWHIV and to identify factors potentially interfering along the HIV-care continuum in southern Mozambique. METHODS: A home-based semi-structured interview was conducted in 2015 to explore barriers and facilitators to the HIV-care cascade among individuals that had been newly HIV-diagnosed in community testing campaigns in 2010 or 2012. Linkage and long-term retention were estimated retrospectively through client self-reports and clinical records. Cohen's Kappa coefficient was calculated to measure the agreement between participant self-reported and documented cascade outcomes. RESULTS: Among the 112 interviewed participants, 24 (21.4%) did not disclose their HIV-positive serostatus to the interviewer. While 84 (75.0%) self-reported having enrolled in care, only 69 (61.6%) reported still being in-care 3-5 years after diagnosis of which 17.4% reported having disengaged and re-engaged. An important factor affecting optimal continuum in HIV-care was the impact of the fear-based authoritarian relationship between the health system and the patient that could act as both driver and barrier. CONCLUSION: Special attention should be given to quantify and understand repeated cycles of patient disengagement and re-engagement in HIV-care. Strategies to improve the relationship between the health system and patients are still needed in order to optimally engage PLWHIV for long-term periods.The author(s) received no specific funding for this work.S

Pediatric HIV care cascade in southern mozambique: Missed opportunities for early ART and re-engagement in care

© 2020 Wolters Kluwer Health, Inc. All rights reserved. Background: There are 170,000 children living with HIV in 2017 in Mozambique. Scaling-up HIV care requires effective retention along the cascade. We sought to evaluate the pediatric cascade in HIV care at the Manhiça District Hospital. Methods: A prospective cohort of children <15 years was followed from enrollment in HIV care (January 2013 to December 2015) until December 2016. Loss to follow-up (LTFU) was defined as not attending the HIV hospital visits for ≥90 days following last visit attended. Results: From the 438 children included {median age at enrollment in care of 3,6 [interquartile range (IQR): 1.1-8.6] years}, 335 (76%) were antiretroviral therapy (ART) eligible and among those, 263 (78%) started ART at enrollment in HIV care. A total of 362 children initiated ART during the study period and the incidence rate of LTFU at 12, 24, and 36 months post-ART initiation was 41 [95% confidence interval (CI): 34-50], 34 (95% CI: 29-41), and 31 (95% CI: 27-37) per 100 children-years, respectively. Median time to LTFU was 5.8 (IQR: 1.4-12.7) months. Children 5-9 years of age had a lower risk of LTFU compared with children <1 year [adjusted subhazard ratio 0.36 (95% CI: 0.20-0.61)]. Re-engagement in care (RIC) was observed in 25% of the LTFU children. Conclusions: The high LTFU found in this study highlights the special attention that should be given to younger children during the first 6 months post-ART initiation to prevent LTFU. Once LTFU, only a quarter of those children return to the health unit. Elucidating factors associated with RIC could help to fine tune interventions which promote RIC

A cytokine pattern that differentiates pre- from post- seroconversion phases of primary HIV infection

During acute HIV infection (AHI) HIV actively replicates but seroconversion has not yet occurred. Primary HIV infection (PHI) is characterized by a transient non-specific febrile illness, a massive inflammatory response and the progressive appearance of anti-HIV specific antibodies. In this study we have identified patterns of inflammatory biomarkers associated with the innate immunological reaction prior to completion of a full humoral response. A symptom-based screening was used to identify AHI in the Manhica District Hospital in Mozambique. Plasma levels of biomarkers were determined by luminex and ELISA. Anti-HIV antibodies were analysed by flow-cytometry and Western blot. Statistical analyses used Random Forest and logistic regression models. Of 3116 rapid test seronegative or indeterminate individuals, 85 (2.7%) had positive plasma HIV viral load and were enrolled as PHI, of which n=45 (52.9%), n=8 (9.4%), n=12 (14.1%) and n=20 (23.5%) were classified as Fiebig I-III, IV, V and VI stages, respectively by Western-blot. Comparison of individuals at early (Fiebig I-IV) and late (Fiebig V-VI) immune stages identified significant differences in the expression level of plasma BAFF, MCP-1, sCD163 and MIG. This cytokine signature classified patients in the pre-seroconversion phase with a sensitivity of 92.5% and a specificity of 81.2% CONCLUSIONS:: Identification of a cytokine signature specific for the pre-seroconversion stage of PHI may help to understand the earliest HIV pathogenic events and identify new potential targets for immunotherapy aimed at modulating the cytokine response to HIV infection.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal

A Longitudinal Analysis Reveals Early Activation and Late Alterations in B Cells During Primary HIV Infection in Mozambican Adults

Altres ajuts: Melinda Gates Foundation (OPP1068252)Primary HIV infection (PHI) and subsequent chronic infection alter B-cell compartment. However, longitudinal analysis defining the dynamics of B-cell alterations are still limited. We longitudinally studied B-cell subsets in individuals followed for 1 year after PHI (n = 40). Treated and untreated chronic HIV infected (n = 56) and HIV-uninfected individuals (n = 58) were recruited as reference groups at the Manhiça District in Mozambique. B cells were analyzed by multicolor flow-cytometry. Anti-HIV humoral response and plasma cytokines were assessed by ELISA or Luminex-based technology. A generalized activation of B cells induced by HIV occurs early after infection and is characterized by increases in Activated and Tissue-like memory cells, decreases in IgM-IgD- (switched) and IgM-only B cells. These alterations remain mostly stable until chronic infection and are reverted in part by ART. In contrast, other parameters followed particular dynamics: PD-1 expression in memory cells decreases progressively during the first year of infection, Transitional B cells expand at month 3-4 after infection, and Marginal zone-like B cells show a late depletion. Plasmablasts expand 2 months after infection linked to plasma viral load and anti-p24 IgG3 responses. Most of well-defined changes induced by HIV in B-cell activation and memory subsets are readily observed after PHI, lasting until ART initiation. However, subsequent changes occur after sustained viral infection. These data indicate that HIV infection impacts B cells in several waves over time, and highlight that early treatment would result in beneficial effects on the B-cell compartment

Discordant retention of HIV-infected mothers and children: Evidence for a family-based approach from Southern Mozambique

It is often assumed that children and their caregivers either stay in care together or discontinue together, but data is lacking on caregiver-child retention concordance. We sought to describe the pattern of care among a cohort of human immunodeficiency virus (HIV) infected children and mothers enrolled in care at the Manhi\xC3\xA7a District Hospital (MDH).This was a retrospective review of routine HIV clinical data collected under a larger prospective HIV cohort study at MDH. Children enrolling HIV care from January 2013 to November 2016 were identified and matched to their mother's HIV clinical data. Retention in care for mothers and children was assessed at 24 months after the child's enrolment. Multinomial logistic regression was performed to evaluate variables associated with retention discordance.For the 351 mother-child pairs included in the study, only 39% of mothers had concordant care status at baseline (23% already active in care, 16% initiated care concurrently with their children). At 24-months follow up, a total of 108 (31%) mother-child pairs were concordantly retained in care, 88 (26%) pairs were concordantly lost to follow up (LTFU), and 149 (43%) had discordant retention. Pairs with concurrent registration had a higher probability of being concordantly retained in care. Children who presented with advanced clinical or immunological stage had increased probability of being concordantly LTFU.High rates of LTFU as well as high proportions of discordant retention among mother-child pairs were found. Prioritization of a family-based care model that has the potential to improve retention for children and caregivers is recommended.

HIV infection and placental malaria reduce maternal transfer of multiple antimalarial antibodies in Mozambican women

Objectives: Maternal Plasmodium falciparum-specific antibodies may contribute to protect infants against severe malaria. Our main objective was to evaluate the impact of maternal HIV infection and placental malaria on the cord blood levels and efficiency of placental transfer of IgG and IgG subclasses.Methods: In a cohort of 341 delivering HIV-negative and HIV-positive mothers from southern Mozambique, we measured total IgG and IgG subclasses in maternal and cord blood pairs by quantitative suspension array technology against eight P. falciparum antigens: Duffy-binding like domains 3-4 of VAR2CSA from the erythrocyte membrane protein 1, erythrocyte-binding antigen 140, exported protein 1 (EXP1), merozoite surface proteins 1, 2 and 5, and reticulocyte-binding-homologue-4.2 (Rh4.2). We performed univariable and multivariable regression models to assess the association of maternal HIV infection, placental malaria, maternal variables and pregnancy outcomes on cord antibody levels and antibody transplacental transfer.Results: Maternal antibody levels were the main determinants of cord antibody levels. HIV infection and placental malaria reduced the transfer and cord levels of IgG and IgG1, and this was antigen-dependent. Low birth weight was associated with an increase of IgG2 in cord against EXP1 and Rh4.2.Conclusions: We found lower maternally transferred antibodies in HIV-exposed infants and those born from mothers with placental malaria, which may underlie increased susceptibility to malaria in these children

HIV infection and placental malaria reduce maternal transfer of multiple antimalarial antibodies in Mozambican women

Objectives: Maternal Plasmodium falciparum-specific antibodies may contribute to protect infants against severe malaria. Our main objective was to evaluate the impact of maternal HIV infection and placental malaria on the cord blood levels and efficiency of placental transfer of IgG and IgG subclasses. Methods: In a cohort of 341 delivering HIV-negative and HIV-positive mothers from southern Mozambique, we measured total IgG and IgG subclasses in maternal and cord blood pairs by quantitative suspension array technology against eight P. falciparum antigens: Duffy-binding like domains 3-4 of VAR2CSA from the erythrocyte membrane protein 1, erythrocyte-binding antigen 140, exported protein 1 (EXP1), merozoite surface proteins 1, 2 and 5, and reticulocyte-binding-homologue-4.2 (Rh4.2). We performed univariable and multivariable regression models to assess the association of maternal HIV infection, placental malaria, maternal variables and pregnancy outcomes on cord antibody levels and antibody transplacental transfer. Results: Maternal antibody levels were the main determinants of cord antibody levels. HIV infection and placental malaria reduced the transfer and cord levels of IgG and IgG1, and this was antigen-dependent. Low birth weight was associated with an increase of IgG2 in cord against EXP1 and Rh4.2. Conclusions: We found lower maternally transferred antibodies in HIV-exposed infants and those born from mothers with placental malaria, which may underlie increased susceptibility to malaria in these children. © 2021 The British Infection Associatio