Reasons for non-disclosure of HIV-Positive status to healthcare providers: a mixed methods study in Mozambique.

BACKGROUND: Non-disclosure of known HIV status by people living with HIV but undergoing HIV testing leads to waste of HIV testing resources and distortion of estimates of HIV indicators. In Mozambique, an estimated one-third of persons who tested positive already knew their HIV-positive status. To our knowledge, this study is the first to assess the factors that prevent people living with HIV (PLHIV) from disclosing their HIV-positive status to healthcare providers during a provider-initiated counseling and testing (PICT) campaign. METHODS: This analysis was nested in a larger PICT cross-sectional study performed in the Manhiça District, Southern Mozambique from January to July 2019, in which healthcare providers actively asked patients about their HIV-status. Patients who tested positive for HIV were crosschecked with the hospital database to identify those who had previously tested positive and were currently or previously enrolled in care. PLHIV who did not disclose their HIV-positive status were invited to participate and provide consent, and were interviewed using a questionnaire designed to explore barriers, patterns of community/family disclosure, and stigma and discrimination. RESULTS: We found that 16.1% of participants who tested positive during a PICT session already knew their HIV-positive status but did not disclose it to the healthcare provider. All the participants reported previous mistreatment by general healthcare providers as a reason for nondisclosure during PICT. Other reasons included the desire to know if they were cured (33.3%) or to re-engage in care (23.5%). Among respondents, 83.9% reported having disclosed their HIV-status within their close community, 48.1% reported being victims of verbal or physical discrimination following their HIV diagnosis, and 46.7% reported that their HIV status affected their daily activities. CONCLUSION: Previous mistreatment by healthcare workers was the main barrier to disclosing HIV-positive status. The high proportion of those disclosing their HIV status to their community but not to healthcare providers suggests that challenges with patient-provider relationships affect this care behavior rather than social stigma and discrimination. Improving patient-provider relationships could increase trust in healthcare providers, reduce non-disclosures, and help optimize resources and provide accurate estimates of the UNAIDS first 95 goal.

Costs and cost-effectiveness of HIV counselling and testing modalities in Southern Mozambique.

OBJECTIVE: Despite the high HIV associated burden, Mozambique lacks data on HIV counselling and testing (HCT) costs. To help guide national HIV/AIDS programs, we estimated the cost per test for voluntary counselling and testing (VCT) from the patient's perspective and the costs per person tested and per HIV-positive individual linked to care to the healthcare provider for VCT, provider-initiated counselling and testing (PICT) and home-based testing (HBT). We also assessed the cost-effectiveness of these strategies for linking patients to care. METHODS: Data from a cohort study conducted in the Manhiça District were used to derive costs and linkage-to-care outcomes of the three HCT strategies. A decision tree was used to model HCT costs according to the likelihood of HCT linking individuals to care and to obtain the incremental cost-effectiveness ratios (ICERs) of PICT and HBT with VCT as the comparator. Sensitivity analyses were performed to assess robustness of base-case findings. FINDINGS: Based on costs and valuations in 2015, average and median VCT costs to the patient per individual tested were US$1.34 and US$1.08, respectively. Costs per individual tested were greatest for HBT (US$11.07), followed by VCT (US$7.79), and PICT (US$7.14). The costs per HIV-positive individual linked to care followed a similar trend. PICT was not cost-effective in comparison with VCT at a willingness-to-accept threshold of US$4.53, but only marginally given a corresponding base-case ICER of US$4.15, while HBT was dominated, with higher costs and lower impact than VCT. Base-case results for the comparison between PICT and VCT presented great uncertainty, whereas findings for HBT were robust. CONCLUSION: PICT and VCT are likely equally cost-effective in Manhiça. We recommend that VCT be offered as the predominant HCT strategy in Mozambique, but expansion of PICT could be considered in limited-resource areas. HBT without facilitated linkage or reduced costs is unlikely to be cost-effective.

Beyond viral suppression: Quality of life among stable ART clients in a differentiated service delivery intervention in Tanzania.

BACKGROUND: With antiretroviral therapy, more people living with HIV (PLHIV) in resource-limited settings are virally suppressed and living longer. WHO recommends differentiated service delivery (DSD) as an alternative, less resource-demanding way of expanding HIV services access. Monitoring client's health-related quality of life (HRQoL) is necessary to understand patients' perceptions of treatment and services but is understudied in sub-Saharan Africa. We assessed HRQoL among ART clients in Tanzania accessing two service models. METHODS: Cross-sectional survey from May-August 2019 among stable ART clients randomly sampled from clinics and clubs in the Shinyanga region providing DSD and clinic-based care. HRQoL data were collected using a validated HIV-specific instrument-Functional Assessment of HIV infection (FAHI), in addition to socio-demographic, HIV care, and service accessibility data. Descriptive analysis of HRQoL, logistic regression and a stepwise multiple linear regression were performed to examine HRQoL determinants. RESULTS: 629 participants were enrolled, of which 40% accessed DSD. Similar HRQoL scores [mean (SD), p-value]; FAHI total [152.2 (22.2) vs 153.8 (20.6), p 0.687] were observed among DSD and clinic-based care participants. Accessibility factors contributed more to emotional wellbeing among DSD participants compared to the clinic-based care participants (53.4% vs 18.5%, p = < 0.001). Satisfactory (> 80% of maximum score) HRQoL scoring was associated with (OR [95% CI], p-value) being male (2.59 [1.36-4.92], p 0.004) among clinic participants and with urban residence (4.72 [1.70-13.1], p 0.001) among DSD participants. CONCLUSIONS: Similar HRQoL was observed in DSD and clinic-based care. Our research highlights focus areas to identify supporting interventions, ultimately optimizing HRQoL among PLHIV.

Optimizing the World Health Organization algorithm for HIV vertical transmission risk assessment by adding maternal self-reported antiretroviral therapy adherence.

BACKGROUND: The World Health Organization (WHO) risk assessment algorithm for vertical transmission of HIV (VT) assumes the availability of maternal viral load (VL) result at delivery and early viral control 4 weeks after initiating antiretroviral treatment (ART). However, in many low-and-middle-income countries, VL is often unavailable and mothers' ART adherence may be suboptimal. We evaluate the inclusion of the mothers' self-reported adherence into the established WHO-algorithm to identify infants eligible for enhanced post-natal prophylaxis when mothers' VL result is not available at delivery. METHODS: We used data from infants with perinatal HIV infection and their mothers enrolled from May-2018 to May-2020 in Mozambique, South Africa, and Mali. We retrospectively compared the performance of the WHO-algorithm with a modified algorithm which included mothers' adherence as an additional factor. Infants were considered at high risk if born from mothers without a VL result in the 4 weeks before delivery and with adherence <90%. RESULTS: At delivery, 143/184(78%) women with HIV knew their status and were on ART. Only 17(12%) obtained a VL result within 4 weeks before delivery, and 13/17(76%) of them had VL ≥1000 copies/ml. From 126 women on ART without a recent VL result, 99(79%) had been on ART for over 4 weeks. 45/99(45%) women reported suboptimal (< 90%) adherence. A total of 81/184(44%) infants were classified as high risk of VT as per the WHO-algorithm. The modified algorithm including self-adherence disclosure identified 126/184(68%) high risk infants. CONCLUSIONS: In the absence of a VL result, mothers' self-reported adherence at delivery increases the number of identified infants eligible to receive enhanced post-natal prophylaxis.

Achieving global equity for COVID-19 vaccines: Stronger international partnerships and greater advocacy and solidarity are needed.

Peter Figueroa and co-authors advocate for equity in the worldwide provision of COVID-19 vaccines.

Community-based progress indicators for prevention of mother-to-child transmission and mortality rates in HIV-exposed children in rural Mozambique.

BACKGROUND: Eliminating mother-to-child HIV-transmission (EMTCT) implies a case rate target of new pediatric HIV-infections< 50/100,000 live-births and a transmission rate < 5%. We assessed these indicators at community-level in Mozambique, where MTCT is the second highest globally.. METHODS: A cross-sectional household survey was conducted within the Manhiça Health Demographic Surveillance System in Mozambique (October 2017-April 2018). Live births in the previous 4 years were randomly selected, and mother/child HIV-status was ascertained through documentation or age-appropriate testing. Estimates on prevalence and transmission were adjusted by multiple imputation chained equation (MICE) for participants with missing HIV-status. Retrospective cumulative mortality rate and risk factors were estimate by Fine-Gray model. RESULTS: Among 5000 selected mother-child pairs, 3486 consented participate. Community HIV-prevalence estimate in mothers after MICE adjustment was 37.6% (95%CI:35.8-39.4%). Estimates doubled in adolescents aged < 19 years (from 8.0 to 19.1%) and increased 1.5-times in mothers aged < 25 years. Overall adjusted vertical HIV-transmission at the time of the study were 4.4% (95% CI:3.1-5.7%) in HIV-exposed children (HEC). Pediatric case rate-infection was estimated at 1654/100,000 live-births. Testing coverage in HEC was close to 96.0%; however, only 69.1% of them were tested early(< 2 months of age). Cumulative child mortality rate was 41.6/1000 live-births. HIV-positive status and later birth order were significantly associated with death. Neonatal complications, HIV and pneumonia were main pediatric causes of death. CONCLUSIONS: In Mozambique, SPECTRUM modeling estimated 15% MTCT, higher than our district-level community-based estimates of MTCT among HIV-exposed children. Community-based subnational assessments of progress towards EMTCT are needed to complement clinic-based and modeling estimates.

Intersectionality and health-related stigma: insights from experiences of people living with stigmatized health conditions in Indonesia.

BACKGROUND: Health-related stigma is a complex phenomenon, the experience of which intersects with those of other adversities arising from a diversity of social inequalities and oppressive identities like gender, sexuality, and poverty - a concept called "intersectionality". Understanding this intersectionality between health-related stigma and other forms of social marginalization can provide a fuller and more comprehensive picture of stigma associated with health conditions. The main objective of this paper is to build upon the concept of intersectionality in health-related stigma by exploring the convergence of experiences of stigma and other adversities across the intersections of health and other forms of social oppressions among people living with stigmatized health conditions in Indonesia. METHODS: This qualitative study interviewed 40 people affected by either of four stigmatizing health conditions (HIV, leprosy, schizophrenia, and diabetes) in Jakarta and West Java, Indonesia between March and June 2018. Data was analyzed thematically using an integrative inductive-deductive framework approach. RESULTS: The main intersectional inequalities identified by the participants were gender and socioeconomic status (n = 21), followed by religion (n = 13), age (n = 11), co-morbidity (n = 9), disability (n = 6), and sexuality (n = 4). Based on these inequalities/identities, the participants reported of experiencing oppression because of prevailing social norms, systems, and policies (macro-level), exclusion and discrimination from societal actors (meso-level), and self-shame and stigma (micro-level). While religion and age posed adversities that negatively affected participants in macro and meso levels, they helped mitigate the negative experiences of stigma in micro level by improving self-acceptance and self-confidence. CONCLUSION: This study uncovered how the experience of health-related stigma intersects with other oppressions originating from the various social inequalities in an individual's life. The findings highlight the importance of acknowledging and understanding the multi-dimensional aspect of lives of people living with stigmatized health conditions, and warrant integrated multi-level and cross-cutting stigma reduction interventions to address the intersectional oppressions they experience.

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.

Interferon-γ-Inducible Protein 10 (IP-10) as a Screening Tool to Optimize Human Immunodeficiency Virus RNA Monitoring in Resource-Limited Settings.

BACKGROUND: Achieving effective antiretroviral treatment (ART) monitoring is a key determinant to ensure viral suppression and reach the UNAIDS 90-90-90 targets. The gold standard for detecting virological failure is plasma human immunodeficiency virus (HIV) RNA (viral load [VL]) testing; however, its availability is very limited in low-income countries due to cost and operational constraints. METHODS: HIV-1-infected adults on first-line ART attending routine visits at the Manhiça District Hospital, Mozambique, were previously evaluated for virologic failure. Plasma levels of interferon-γ-inducible protein 10 (IP-10) were quantified by enzyme-linked immunosorbent assay. Logistic regression was used to build an IP-10-based model able to identify individuals with VL >150 copies/mL. From the 316 individuals analyzed, 253 (80%) were used for model training and 63 (20%) for validation. Receiver operating characteristic curves were employed to evaluate model prediction. RESULTS: From the individuals included in the training set, 34% had detectable VL. Mean age was 41 years, 70% were females, and median time on ART was 3.4 years. IP-10 levels were significantly higher in subjects with detectable VL (108.2 pg/mL) as compared to those with undetectable VL (38.0 pg/mL) (P < .0001, U test). IP-10 univariate model demonstrated high classification performance (area under the curve = 0.85 [95% confidence interval {CI}, .80-.90]). Using a cutoff value of IP-10 ≥44.2 pg/mL, the model identified detectable VL with 91.9% sensitivity (95% CI, 83.9%-96.7%) and 59.9% specificity (95% CI, 52.0%-67.4%), values confirmed in the validation set. CONCLUSIONS: IP-10 is an accurate biomarker to screen individuals on ART for detectable viremia. Further studies should evaluate the benefits of IP-10 as a triage approach to monitor ART in resource-limited settings.

Association between HIV infection and socio-economic status: evidence from a semirural area of southern Mozambique.

OBJECTIVES: To analyse the association between socio-economic status (SES) and HIV in Manhiça, a district of Southern Mozambique with one of the highest HIV prevalences in the world. METHODS: Data were gathered from two cross-sectional surveys performed in 2010 and 2012 among 1511 adults and from the household census of the district's population. Fractional polynomial logit models were used to analyse the association between HIV and SES, controlling for age and sex and taking into account the nonlinearity of covariates. The inequality of the distribution of HIV infection with regard to SES was computed through a concentration index. RESULTS: Fourth and fifth wealth quintiles, the least poor, were associated with a reduced probability of HIV infection compared to the first quintile (OR = 0.595, P-value = 0.009 and OR = 0.474, P-value < 0.001, respectively). Probability of HIV infection peaked at 36 years and then fell, and was always higher for women regardless of age and SES. HIV infection was unequally distributed across the SES strata. CONCLUSIONS: Despite the high HIV prevalence across the entire population of Manhiça, the poorest are at greatest risk of being HIV infected. While women have a higher probability of being HIV positive than men, both sexes showed the same infection reduction at higher levels of SES. HIV interventions in the area should particularly focus on the poorest and on women without neglecting anyone else, as the HIV risk is high for everyone.

Determinants of virological failure and antiretroviral drug resistance in Mozambique.

OBJECTIVES: The objective of this study was to inform public health actions to limit first-line ART failure and HIV drug resistance in Mozambique. METHODS: This was a cross-sectional study. HIV-1-infected adults on first-line ART for at least 1 year attending routine visits in the Manhiça District Hospital, in a semi-rural area in southern Mozambique with no HIV-1 RNA monitoring available, were evaluated for clinical, socio-demographic, therapeutic, immunological and virological characteristics. Factors associated with HIV-1 RNA ≥1000 copies/mL and HIV drug resistance were determined using multivariate logistic regression. RESULTS: The study included 334 adults on first-line ART for a median of 3 years, of which 65% (214/332) had suppressed viraemia, 11% (37/332) had low-level viraemia (HIV-1 RNA 150-999 copies/mL) and 24% (81/332) had overt virological failure (HIV-1 RNA ≥1000 copies/mL). HIV drug resistance was detected in 89% of subjects with virological failure, but in none with low-level viraemia. Younger age [OR = 0.97 per additional year (95% CI = 0.94-1.00), P = 0.039], ART initiation at WHO stage III/IV [OR = 2.10 (95% CI = 1.23-3.57), P = 0.003] and low ART adherence [OR = 2.69 (95% CI = 1.39-5.19), P = 0.003] were associated with virological failure. Longer time on ART [OR = 1.55 per additional year (95% CI = 1.00-2.43), P = 0.052] and illiteracy [OR = 0.24 (95% CI = 0.07-0.89), P = 0.033] were associated with HIV drug resistance. Compared with HIV-1 RNA, clinician's judgement of ART failure, based on clinical and immunological outcomes, only achieved 29% sensitivity and misdiagnosed 1 out of every 4.5 subjects. CONCLUSIONS: Public health programmes in Mozambique should focus on early HIV diagnosis, early ART initiation and adherence support. Virological monitoring drastically improves the diagnosis of ART failure, enabling a better use of resources.

Impact of elevated maternal HIV viral load at delivery on T-cell populations in HIV exposed uninfected infants in Mozambique.

BACKGROUND: HIV-uninfected infants born to HIV-infected mothers (HIV-exposed uninfected, HEU) have been described to have immune alterations as compared to unexposed infants. This study sought to characterize T-cell populations after birth in HEU infants and unexposed infants living in a semirural area in southern Mozambique. METHODS: Between August 2008 and June 2009 mother-infant pairs were enrolled at the Manhiça District Hospital at delivery into a prospective observational analysis of immunological and health outcomes in HEU infants. Infants were invited to return at one month of age for a clinical examination, HIV DNA-PCR, and immunophenotypic analyses. The primary analysis sought to assess immunological differences between HEU and unexposed groups, whereas the secondary analysis assessed the impact of maternal HIV RNA viral load in the HEU group. Infants who had a positive HIV DNA-PCR test were not included in the analysis. RESULTS: At one month of age, the 74 HEU and the 56 unexposed infants had similar median levels of naïve, memory and activated CD8 and CD4 T-cells. Infant naïve and activated CD8 T-cells were found to be associated with maternal HIV-RNA load at delivery. HEU infants born to women with HIV-RNA loads above 5 log10 copies/mL had lower median levels of naïve CD8 T-cells (p = 0.04), and higher median levels of memory CD8 T-cells, (p = 0.014). CONCLUSIONS: This study suggests that exposure to elevated maternal HIV-RNA puts the infant at higher risk of having early T-cell abnormalities. Improving prophylaxis of mother to child HIV programs such that more women have undetectable viral load is crucial to decrease vertical transmission of HIV, but may also be important to reduce the consequences of HIV virus exposure in HEU infants.

HIV care retention in three multi-month ART dispensing: a retrospective cohort study in Mozambique.

OBJECTIVE: Evaluate the effect of three multimonth dispensing (3MMD) of antiretroviral therapy (ART) on HIV care retention in southern Mozambique. DESIGN: Retrospective cohort study. METHODS: We analyzed routine health data from people with HIV (PWH) aged 10 years old and older who started ART between January 2018 and March 2021. Individuals were followed until December 2021. Cox proportional-hazards models were used to compare attrition (lost to follow-up, death, and transfer out) between 3MMD and monthly ART dispensing. Results were stratified by time on ART before 3MMD enrolment: 'early enrollers' (<6 months on ART) and 'established enrollers' (≥6 months on ART), and age groups: adolescents and youth (AYLHIV) (10-24 years) and adults (≥25 years). RESULTS: We included 7378 PWH (25% AYLHIV, 75% adults), with 59% and 62% enrolled in 3MMD, respectively. Median follow-up time was 11.3 [interquartile range (IQR): 5.7-21.6] months for AYLHIV and 10.2 (IQR: 4.8-20.9) for adults. Attrition was lower in PWH enrolled in 3MMD compared with monthly ART dispensing, in both established (aHR AYLHIV = 0.65; 95% CI: 0.54-0.78 and aHR adults = 0.50; 95% confidence interval (CI): 0.44-0.56) and early enrollers (aHR AYLHIV = 0.70; 95% CI: 0.58-0.85 and aHR adults = 0.63; 95% CI: 0.57-0.70). Among individuals in 3MMD, male gender (aHR = 1.30; 95% CI: 1.18-1.44) and receiving care in a medium-volume/low-volume healthcare facility (aHR = 1.18; 95% CI: 1.03-1.34) increased attrition risk. Conversely, longer ART time before 3MMD enrolment (aHR = 0.93; 95% CI: 0.92-0.94 per 1 month increase) and age at least 45 years (aHR = 0.77, 95% CI: 0.67-0.89) reduced risk of attrition. CONCLUSION: 3MMD improves retention in care compared with monthly dispensing among established and early enrollers, although to a lesser extent among the latter.

Enhancing HIV positivity yield in southern Mozambique: The effect of a Ministry of Health training module in targeted provider-initiated testing and counselling.

In Mozambique, targeted provider-initiated HIV testing and counselling (PITC) is recommended where universal PITC is not feasible, but its effectiveness depends on healthcare providers' training. This study aimed to evaluate the effect of a Ministry of Health training module in targeted PITC on the HIV positivity yield, and identify factors associated with a positive HIV test. We conducted a single-group pre-post study between November 2018 and November 2019 in the triage and emergency departments of four healthcare facilities in Manhiça District, a resource-constrained semi-rural area. It consisted of two two-month phases split by a one-week targeted PITC training module ("observation phases"). The HIV positivity yield of targeted PITC was estimated as the proportion of HIV-positive individuals among those recommended for HIV testing by the provider. Additionally, we extracted aggregated health information system data over the four months preceding and following the observation phases to compare yield in real-world conditions ("routine phases"). Logistic regression analysis from observation phase data was conducted to identify factors associated with a positive HIV test. Among the 7,102 participants in the pre- and post-training observation phases (58.5% and 41.5% respectively), 68% were women, and 96% were recruited at triage. In the routine phases with 33,261 individuals (45.8% pre, 54.2% post), 64% were women, and 84% were seen at triage. While HIV positivity yield between pre- and post-training observation phases was similar (10.9% (269/2470) and 11.1% (207/1865), respectively), we observed an increase in yield in the post-training routine phase for women in triage, rising from 4.8% (74/1553) to 7.3% (61/831) (Yield ratio = 1.54; 95%CI: 1.11-2.14). Age (25-49 years) (OR = 2.43; 95%CI: 1.37-4.33), working in industry/mining (OR = 4.94; 95%CI: 2.17-11.23), unawareness of partner's HIV status (OR = 2.50; 95%CI: 1.91-3.27), and visiting a healer (OR = 1.74; 95%CI: 1.03-2.93) were factors associated with a positive HIV test. Including these factors in the targeted PITC algorithm could have increased new HIV diagnoses by 2.6%. In conclusion, providing refresher training and adapting the current targeted PITC algorithm through further research can help reach undiagnosed PLHIV, treat all, and ultimately eliminate HIV, especially in resource-limited rural areas.

High mortality following early initiation of antiretroviral therapy in infants living with HIV from three African countries.

Background: Even with increasing access to rapid HIV diagnosis and early antiretroviral therapy (ART) initiation, infants living with HIV seem to have adverse outcomes. We assessed the probability of death, viral suppression, and other HIV-related events in the first three years of life among early-treated children with perinatally-acquired HIV in South Africa, Mozambique, and Mali. Methods: We enrolled a cohort of infants who initiated ART within the initial 6 months of life and within 3 months of diagnosis. These children were monitored 2, 6, 12 and 24 weeks after enrolment, followed by biannual check-ups up to 4 years after enrolment. We assessed the probability of death, viral load (VL) suppression, severe immunosuppression (according to WHO guidelines), and engagement in care using Kaplan-Meier plots, and hazard ratios for these outcomes using multivariable Cox regression models. Findings: Two hundred and fifteen infants were enrolled and monitored for a median of 34 months [IQR, 16.3; 44.1]. ART initiation occurred at a median of 34 days of age [IQR, 26.0; 73.0]. The probability of death at 1 year of ART was 10% (95% CI, 6-14), increased to 12% (95% CI, 8-17) at 2 and remained in 12% at 3 years. The main risk factor for HIV/AIDS-related mortality was baseline viral load [HR: 2.98 (95% CI, 1.25-7.12)]. Sixty-one of 146 (42%) children achieved sustained virological control below lower limit of detection for any ≥1 year period between enrolment and 4 years after enrolment. Viral suppression during follow-up was inversely associated with baseline viral load [Hazard Ratio (HR): 0.72 (95% CI, 0.58-0.89] and adverse maternal social events [HR: 0.26 (95% CI, 0.15-0.45)]. Adherence to ART was assessed as optimal in 81% of the visits. Female sex at birth, lower age at diagnosis and maternal adverse social life events were risk factors for low adherence [Odds ratio, OR 1.25 (95% CI, 1.00-1.56); 1.12 (95% CI, 1.01-1.27) and 2.52 (95% CI, 2.16-12.37), respectively]. Interpretation: Despite early ART, mortality remains high in infants. High baseline VL and adverse maternal social environment increased the risk of poor outcomes. Sustained supportive strategies are essential during and after pregnancy, to achieve better survival. Funding: Early Treated Perinatally HIV Infected Individuals: Improving Children's Actual Life (EPIICAL) is a research consortium funded by ViiV Healthcare and led by Penta Foundation. The funder was not involved in the analysis and interpretation of data, writing of the report, or the decision to submit the paper for publication. The corresponding authors had access to all data and take final responsibility for the decision to submit.

Reduction of antimalarial antibodies by HIV infection is associated with increased risk of Plasmodium falciparum cord blood infection.

BACKGROUND: Plasmodium falciparum infection in pregnancy can lead to congenital malaria, which has detrimental health consequences for infants. Human immunodeficiency virus (HIV) might increase cord blood P. falciparum infection by decreasing maternal antimalarial-specific antibodies. METHODS: HIV-negative (n=133) and HIV-positive (n=55) Mozambican pregnant women were assessed at delivery for maternal and cord P. falciparum infection by quantitative polymerase chain reaction (qPCR) and P. falciparum-specific antibodies by enzyme-linked immunosorbent assay and flow cytometry. RESULTS: Prevalence of qPCR-detected cord blood infection was 8.0%. Risk of cord infection was increased in presence of HIV (adjusted odds ratio [AOR], 3.80; P=.04) and placental malaria (AOR, 22.08; P=.002) after adjusting for clinical variables. The odds of having a high immunoglobulin G response to chondrotin sulphate A-binding infected erythrocytes, parasite lysate, and erythrocyte-binding antigen-175 were reduced among HIV-positive women (P < .001, .048, and .056, respectively) and among women with cord P. falciparum infection (P = .009, .04, and .046, respectively). In multivariate analysis including maternal HIV status, placental malaria, and antibody responses, HIV was no longer associated with cord blood infection (P = .11). CONCLUSIONS: HIV-associated impairment of antibody responses in pregnant women may contribute to a higher transmission of P. falciparum to their infants.

Field performance and cost-effectiveness of a point-of-care triage test for HIV virological failure in Southern Africa.

INTRODUCTION: Antiretroviral therapy (ART) monitoring using viral load (VL) testing is challenging in high-burden, limited-resources settings. Chemokine IP-10 (interferon gamma-induced protein 10) strongly correlates with human immunodeficiency virus (HIV) VL. Its determination could serve to predict virological failure (VF) and to triage patients requiring VL testing. We assessed the field performance of a semi-quantitative IP-10 lateral flow assay (LFA) for VF screening in South Africa, and the cost-effectiveness of its implementation in Mozambique. METHODS: A cross-sectional study was conducted between June and December 2021 in three primary health clinics in the Western Cape. Finger prick capillary blood was collected from adults on ART for ≥1 year for direct application onto the IP-10 LFA (index test) and compared with a plasma VL result ≤1 month prior (reference test). We estimated the area under the receiver operating characteristic curves (AUC), sensitivity and specificity, to evaluate IP-10 LFA prediction of VF (VL>1000 copies/ml). A decision tree model was used to investigate the cost-effectiveness of integrating IP-10 LFA combined with VL testing into the current Mozambican ART monitoring strategy. Averted disability-adjusted life years (DALYs) and HIV acquisitions, and incremental cost-effectiveness ratios were estimated. RESULTS: Among 209 participants (median age 38 years and 84% female), 18% had VF. Median IP-10 LFA values were higher among individuals with VF compared to those without (24.0 vs. 14.6; p<0.001). The IP-10 LFA predicted VF with an AUC = 0.76 (95% confidence interval (CI) 0.67-0.85), 91.9% sensitivity (95% CI 78.1-98.3) and 35.1% specificity (95% CI 28.0-42.7). Integrating the IP-10 LFA in a setting with 20% VF prevalence and 61% VL testing coverage could save 13.0% of costs and avert 14.9% of DALYs and 55.7% new HIV acquisitions. Furthermore, its introduction was estimated to reduce the total number of routine VL tests required for ART monitoring by up to 68%. CONCLUSIONS: The IP-10 LFA is an effective VF triage test for routine ART monitoring. Combining a highly sensitive, low-cost IP-10 LFA-based screening with targeted VL confirmatory testing could result in significant healthcare quality improvements and cost savings in settings with limited access to VL testing.

Gene dysregulation in acute HIV-1 infection - early transcriptomic analysis reveals the crucial biological functions affected.

Introduction: Transcriptomic analyses from early human immunodeficiency virus (HIV) infection have the potential to reveal how HIV causes widespread and lasting damage to biological functions, especially in the immune system. Previous studies have been limited by difficulties in obtaining early specimens. Methods: A hospital symptom-based screening approach was applied in a rural Mozambican setting to enrol patients with suspected acute HIV infection (Fiebig stage I-IV). Blood samples were collected from all those recruited, so that acute cases and contemporaneously recruited, uninfected controls were included. PBMC were isolated and sequenced using RNA-seq. Sample cellular composition was estimated from gene expression data. Differential gene expression analysis was completed, and correlations were determined between viral load and differential gene expression. Biological implications were examined using Cytoscape, gene set enrichment analysis, and enrichment mapping. Results: Twenty-nine HIV infected subjects one month from presentation and 46 uninfected controls were included in this study. Subjects with acute HIV infection demonstrated profound gene dysregulation, with 6131 (almost 13% of the genome mapped in this study) significantly differentially expressed. Viral load was correlated with 1.6% of dysregulated genes, in particular, highly upregulated genes involved in key cell cycle functions, were correlated with viremia. The most profoundly upregulated biological functions related to cell cycle regulation, in particular, CDCA7 may drive aberrant cell division, promoted by overexpressed E2F family proteins. Also upregulated were DNA repair and replication, microtubule and spindle organization, and immune activation and response. The interferome of acute HIV was characterized by broad activation of interferon-stimulated genes with antiviral functions, most notably IFI27 and OTOF. BCL2 downregulation alongside upregulation of several apoptotic trigger genes and downstream effectors may contribute to cycle arrest and apoptosis. Transmembrane protein 155 (TMEM155) was consistently highly overexpressed during acute infection, with roles hitherto unknown. Discussion: Our study contributes to a better understanding of the mechanisms of early HIV-induced immune damage. These findings have the potential to lead to new earlier interventions that improve outcomes.