Occupational barriers to HIV care in female sex workers living with HIV: structural or community solutions?

The UNAIDS 90-90-90 targets, defined as 90% of people living with HIV aware of their status, among which 90% are on antiretroviral treatment (ART) and among which 90% have HIV viral suppression, have galvanised efforts worldwide to reduce HIV transmission with the goal of ending the HIV epidemic by 2030. Sex workers, who are particularly vulnerable to HIV, and their sexual partners account for more than half (54%) of new HIV infections globally.1 Available data suggest that the relative risk of HIV acquisition among sex workers globally was 21 times higher than it was among all adults aged 15–49 years in 2018.1 Still, ART utilisation is poor among female sex workers (FSWs) globally—with an estimated 38% and 57% pooled prevalence for current ART use and viral suppression, respectively.2 With the goal of ending the AIDS epidemic by 2030, the critical question is how to increase the 90-90-90 targets, including awareness of HIV status, initiation and adherence to ART among sex workers

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

c-Jun NH2-Terminal Kinase (JNK)1 and JNK2 Signaling Pathways Have Divergent Roles in CD8+ T Cell–mediated Antiviral Immunity

c-Jun NH2-terminal kinases (JNK) play important roles in T helper cell (Th) proliferation, differentiation, and maintenance of Th1/Th2 polarization. To determine whether JNKs are involved in antiviral T cell immunity, and whether JNK1 and JNK2 bear biological differences, we investigated the immune responses of JNK1-deficient and JNK2-deficient mice to lymphocytic choriomeningitis virus (LCMV). After LCMV infection, wild-type (JNK+/+) mice had a 5- to 10-fold increase in splenic CD8+ T cells. In contrast, infected JNK1−/− mice showed a significantly lower virus-specific CD8+ T cell expansion. However, JNK1−/− mice cleared LCMV infection with similar kinetics as JNK+/+ mice. Splenic T cells from LCMV-infected JNK1−/− animals produced interferon γ after stimulation with viral peptides. However, fewer JNK1−/− T cells acquired an activated phenotype (CD44hi) and more JNK1−/−CD8+CD44hi cells underwent apoptosis than JNK+/+ cells at the peak of the primary response. In contrast, LCMV-infected JNK2−/− mice generated more virus-specific CD8+ T cells than JNK+/+ mice. These results indicate that JNK1 and JNK2 signal pathways have distinct roles in T cell responses during a viral infection. JNK1 is involved in survival of activated T cells during immune responses, and JNK2 plays a role in control of CD8+ T cell expansion in vivo

Impact of Maternal Human Immunodeficiency Virus Infection on Birth Outcomes and Infant Survival in Rural Mozambique

Sub-Saharan Africa harbors more than two-thirds of the world’s 33.2 million persons infected with human immunodeficiency virus (HIV) and 80% of the world’s HIV-infected women. In parts of southern Africa, more than 30% of pregnant women attending antenatal clinics are infected with HIV, thus making HIV infection one of the most common complications of pregnancy in sub-Saharan Africa. With successful interventions, mother-to-child transmission (MTCT) of HIV has been reduced to less than 2% in developed countries. However, in untreated populations, MTCT of HIV during pregnancy, delivery, and breastfeeding still occurs at an approximate overall rate of 25–40%, and accounts for almost 420,000 new HIV infections in children and 270,000–320,000 pediatric deaths annually. Until 2004, single-dose intrapartum and neonatal nevirapine (sd-NVP) was the recommended regimen by the World Health Organization to prevent MTCT of HIV among women without access to antiretroviral therapy. Preventive MTCT programs with an sd-NVP have been shown to decrease perinatal HIV transmission to 8% in controlled clinical trial settings. However, there is great concern about the rapid development of resistance. In addition, in predominantly breastfeeding populations of sub- Saharan Africa, most MTCT of HIV still occurs during the postnatal period. Currently, MTCT prevention programs in sub-Saharan African countries include zidovudine and lamivudine during the final weeks of pregnancy and sd-NVP at delivery. In addition, the newborn receives sd-NVP at birth and zidovudine for seven days. Nevertheless, effectiveness of these strategies relies on the great challenge of availability of the drugs and compliance with them, given that these preventive regimens are prolonged and unsupervised. Several studies from the Africa have reported that HIVinfected pregnant women are at increased risk of adverse pregnancy outcomes such as spontaneous abortion, stillbirths, and preterm labor. However, this analysis is complicated by many factors associated with HIV infection and poor pregnancy outcomes such as malnutrition, anemia, and other frequent infections such as syphilis or malaria. These factors may contribute to the observation that the association between HIV infection and adverse pregnancy outcomes is stronger in women from developing countries. Maternal HIV infection has also been associated with an increased risk of infant death. It is well documented that up to 35% of HIV-infected infants may die before the first year of age, but HIV-negative children born to HIV-infected mothers are also at high risk of mortality. There have been few studies characterizing the impact of HIV infection during pregnancy on the mother and her infant and even fewer from rural African settings. The main aim of this study was to assess the impact of HIV infection on birth outcomes and infant survival in a rural area of southern Mozambique. Furthermore, the study also evaluated the effect of unsupervised sd-NVP administration for prevention of MTCT of HIV on HIV RNA viral load at delivery and the prevalence of NVP resistance mutations

Incidence and predictors of immune reconstitution inflammatory syndrome in a rural area of Mozambique.

There is limited data on the epidemiology of Immune Reconstitution Inflammatory Syndrome (IRIS) in rural sub-Saharan Africa. A prospective observational cohort study was conducted to assess the incidence, clinical characteristics, outcome and predictors of IRIS in rural Mozambique

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

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

Recent HIV-1 Infection: Identification of Individuals with High Viral Load Setpoint in a Voluntary Counselling and Testing Centre in Rural Mozambique

Background: Identification of recent HIV-infections is important for describing the HIV epidemic and compiling HIV-RNA-setpoint data for future HIV intervention trials. We conducted a study to characterize recent infections, and HIV-RNA-setpoint within the adult population presenting at a voluntary counselling and testing centre (VCT) in southern Mozambique. Methods: All adults attending the Manhiça District-Hospital VCT between April and October 2009 were recruited if they had at least one positive rapid HIV-serology test. Patients were screened for recent HIV-1 infection by BED-CEIA HIV-incidence test. Clinical examination, assessment of HIV-RNA and CD4 cell counts were performed at enrollment, 4 and 10 months. Results: Of the 492 participants included in this study, the prevalence of recent infections as defined by BED-CEIA test, CD4 counts >200 cells/µl and HIV-RNA >400 copies/mL, was 11.58% (57/492; 95% CI 8.89-14.74). Due to heterogeneity in HIV-RNA levels in recently infected patients, individuals were categorized as having "high" HIV-RNA load if their HIV-RNA level was above the median (4.98 log10 copies/mL) at diagnosis. The "high" HIV-RNA group sustained a significantly higher HIV-viral load at all visits with a median HIV-RNA setpoint of 5.22 log10 copies/mL (IQR 5.18-5.47) as compared to the median of 4.15 log10 copies/ml (IQR 3.37-4.43) for the other patients (p = 0.0001). Conclusion: The low proportion of recent HIV-infections among HIV-seropositive VCT clients suggests that most of this population attends the VCT at later stages of HIV/AIDS. Characterization of HIV-RNA-setpoint may serve to identify recently infected individuals maintaining HIV viral load>5 log10 copies/mL as candidates for antiretroviral treatment as prevention interventions

High tuberculosis burden among people living with HIV in southern Mozambique

Tuberculosis (TB) remains an important public health concern, and a leading cause of disease and death worldwide. Mozambique is one of the few high TB burden countries where TB figures have not improved in recent years, with an estimated TB incidence in 2013 of 552 cases per 100 000 population [1]. With 58% of all notified TB cases being HIV-positive, Mozambique also has one of the highest TB/HIV co-infection rates. Published data on the burden of TB or HIV disease in the country are scarce, and improving epidemiological surveillance has been identified as an urgent step to improve TB control [2]

Interferon-gamma-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 Manhica District Hospital, Mozambique, were previously evaluated for virologic failure. Plasma levels of interferon-gamma-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