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Objective: AIDS-defining illness develops at higher CD4 + T-cell counts in individuals infected with HIV-2 compared with HIV-1-infected, which suggests that the two types of HIV may have different effects on other compartments of the immune system. We here investigate monocyte phenotype, activation and macrophage-derived extracellular vesicles in individuals with different HIV types., Design: Cross-sectional., Methods: ART-naive HIV-1 ( n  = 83), HIV-2 ( n  = 63), and HIV-1/2 dually positive ( n  = 27) participants were recruited in Bissau, Guinea-Bissau, together with HIV-negative controls ( n  = 26). Peripheral blood mononuclear cells (PBMCs) were isolated and analyzed by flow cytometry for monocyte phenotype and activation, and plasma was analyzed for extracellular vesicle forms of CD163 and CD206., Results: Compared with HIV-negative controls, all groups of HIV-positive participants had a skewed monocyte phenotype with a higher proportion of intermediate monocytes, increased CD163 expression and elevated serum levels of the inflammatory biomarkers soluble (s)CD163 and sCD206. HIV-2-positive participants had lower CD163 monocyte expression than HIV-1-positive participants, regardless of HIV RNA or CD4 + cell count. Levels of sCD206 extracellular vesicles were increased in all HIV groups, and higher in HIV-1 compared with HIV-2-positive participants., Conclusion: The monocyte phenotype of HIV-2-positive participants deviated less from healthy controls than did HIV-1 participants. HIV-2-positive participants also had a lower concentration of extracellular CD206 vesicles compared with HIV-1-positive participants. This does not explain the difference in AIDS development., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: In the 2020 UNAIDS HIV treatment goals, 90% of people living with HIV (PLHIV) should be diagnosed, 90% of these should receive antiretroviral treatment (ART) and 90% of these should be virally suppressed. We aimed to evaluate whether Guinea-Bissau fulfills the 2020 treatment goals for both for HIV-1 and HIV-2., Design: By combining data from a general population survey, treatment records from HIV clinics across Guinea-Bissau and a biobank from patients attending the largest HIV clinics in Bissau, we estimated each column of the 90-90-90 cascade., Method: 2601 participated in the survey and were used to estimate the proportion of PLHIV who knew their HIV status and the proportion of PLHIV on ART. Answers given in the survey was verified with treatment records from HIV clinics. We measured viral load from biobank materials from HIV patients and estimated the proportion of virally suppressed PLHIV., Result: 19.1% of PLHIV indicated to be aware of their HIV status. Of these, 48.5% received ART, and 76.4% of these were virally suppressed. For HIV-1 and HIV-1/2 the results were 21.2%, 40.9% and 75.1%. For HIV-2 the results were 15.9%, 63.6% and 80.7%. 26.9% of all HIV-1 infected in the survey were virologically suppressed, indicating that a much higher number of HIV-1 infected were aware of their status and on treatment., Conclusion: Guinea-Bissau lags severely behind both the global and regional progress. Improvement in both testing and treating HIV is necessary to improve the quality of care., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

The human immunodeficiency virus (HIV) remains a leading cause of maternal morbidity and mortality in Sub-Saharan Africa. Prevention of mother-to-child transmission (PMTCT) has proven an effective strategy to end paediatric infections and ensure HIV-infected mothers access treatment. Based on cross-sectional data collected from June 2008 to May 2013, we assessed changes in HIV prevalence, risk factors for HIV, provision of PMTCT antiretroviral treatment (ART), and the association between HIV infection, birth outcomes and maternal characteristics at the Simão Mendes National Hospital, Guinea-Bissau's largest maternity ward. Among 24,107 women, the HIV prevalence was 3.3% for HIV-1, 0.8% for HIV-2 and 0.9% for HIV-1/2. A significant decline in HIV-1, HIV-2, and HIV-1/2 prevalence was observed over time. HIV infection was associated with age and ethnicity. A total of 85% of HIV-infected women received ART as part of PMTCT, yet overall treatment coverage during labour and delivery declined significantly for both mothers and infants. Twenty-two percent of infants did not receive treatment, and 67% of HIV-2-infected mothers and 77% of their infants received ineffective non-nucleoside reverse transcriptase inhibitors for PMTCT. Maternal HIV was associated with low birth weight but not stillbirth. Inadequate continuity of care and ART coverage present challenges to optimal PMTCT in Guinea-Bissau.

Background: HIV-2 may slow progression of a subsequently acquired HIV-1 infection through cross-neutralizing antibodies and polyfunctional CD8 T cells. We hypothesized that HIV-1/2 dually infected patients compared with HIV-1-infected patients had more preserved immune maturation subsets and less immune activation of T and B cells., Methods: ART-naive patients with HIV-1 (n = 83) or HIV-1/2 dual (n = 27) infections were included in this cross-sectional study at an HIV clinic in Guinea-Bissau. Peripheral blood mononuclear cells (PBMCs) were analyzed by flow cytometry according to T-cell maturation and activation, regulatory T-cell fraction, and B-cell maturation and activation., Results: HIV-1/2 dually infected patients had lower levels of HIV-1 RNA compared with patients with HIV-1 infection, but the levels of total HIV RNA (HIV-1 and HIV-2) were similar in the two patient groups. T-cell maturation, and proportions of regulatory T cells (FoxP3+) were also similar in the two groups. HIV-1/2 dually infected patients had higher proportions of CD4 and CD8 T cells positive for the activation marker CD38, but there was no difference in other T-cell activation markers (CD28, CTLA-4, PD-1). HIV-1/2 dually infected patients also had higher proportions of IgM-only B cells and plasmablasts., Conclusion: HIV-1/2 was not associated with less immune perturbations than for HIV-1 infection.

Background: For unknown reasons, HIV-2 is less pathogenic than HIV-1, and HIV-2-induced immunodeficiency may be different from that caused by HIV-1. Previous immunological studies have hinted at possible shifts in both T-cell and B-cell subsets, which we aimed to characterize further., Methods: From an HIV clinic in Guinea-Bissau, 63 HIV-2, 83 HIV-1, and 26 HIV-negative participants were included. All HIV-infected participants were ART-naive. The following cell subsets were analysed by flow cytometry; T cells (maturation and activation), regulatory T cells, and B cells (maturation and activation)., Results: After standardizing for sex, age, and CD4 T-cell count HIV-2 had 0.938 log10 copies/ml lower HIV RNA levels than the HIV-1-infected patients. Whereas T-cell maturation and regulatory T-cell profiles were similar between patients, HIV-2-infected patients had higher proportions of CD8CD28 and lower proportions of CD8PD-1+ T cells than HIV-1-infected patients. This finding was independent of HIV RNA levels. HIV-2 was also associated with a more preserved proportion of naive B cells., Conclusion: HIV-2 is characterized by lower viral load, and lower T-cell activation, which may account for the slower disease progression.

Macrophages play important roles during human immunodeficiency virus (HIV) infection, reflected by changes in macrophage-activation biomarker soluble CD163 (sCD163). Here, we present data on the novel macrophage-activation biomarker soluble mannose receptor/CD206 (sCD206) in HIV infection. We investigated sCD206 blood levels at baseline and follow-up with/without antiretroviral therapy (ART), in 212 patients with HIV type 1 (HIV-1), HIV type 2 (HIV-2), or dual infection. At baseline, there was no difference in sCD206 level between HIV types, and sCD206 was unchanged at follow-up without ART. However, in contrast to sCD163, sCD206 levels decreased significantly for both HIV-1 and HIV-2, but not for HIV-1/2 patients, during ART. Further investigations are needed to establish sCD206 as a biomarker in HIV infection.

Objective: Although Guinea-Bissau has the world's highest prevalence of HIV-2, it has been decreasing since 1987. Meanwhile, the prevalence of HIV-1 has been increasing. We describe both the prevalence and changes in incidence of HIV-2 and HIV-1 during the last 30 years of observation in the capital Bissau in Guinea-Bissau., Methods: A total of 3125 adults living in 412 houses in Bissau were eligible for inclusion in the present cross-sectional survey conducted from November 2014 to February 2016. All participants had a questionnaire filled out and a blood sample taken. Results were compared with previous surveys., Results: Of the 3125 eligible adults, 2601 (83.2%) individuals participated. The overall prevalence of HIV decreased from 8.6% (218/2548) in 2006 to 6.7% (173/2601) in 2016 with an age-adjusted and sex-adjusted prevalence ratio (aPR) of 0.71 [95% confidence interval (CI) = 0.59-0.85]. Including HIV-1/2 dual infections, a decrease in the overall prevalence of HIV-2 from 4.4% (112/2548) to 2.8% (72/2601) was observed with an aPR of 0.55 (95% CI = 0.41-0.73). The overall prevalence of HIV-1 decreased from 4.6% (118/2548) to 4% (104/2601) with an aPR of 0.81 (95% CI = 0.63-1.05). Incidence rates for HIV-2 and HIV-1, estimated for 815 individuals, decreased from 0.24 to 0.09 and from 0.50 to 0.40 per 100 person-years of observation, respectively, in the periods between 1996-2006 and 2006-2016., Conclusion: The prevalence of HIV-2 continues to decrease, whereas the prevalence of HIV-1 showed sign of stabilization. The results observed may be explained by a lower pathogenicity of HIV-2 and changes in risk behavior.

Introduction: HIV infected individuals with late presentation (LP) and advanced disease (AD) have been associated with higher mortality, higher cost of medical management, impaired CD4 cell count increment and potentially ongoing risk of HIV transmission. Here we describe the proportion of patients with LP and AD at an HIV clinic in Guinea-Bissau, identify risk factors and evaluate the outcome of these patients., Methods: We included all patients >15 years diagnosed with HIV-1 and/or HIV-2 at the outpatient HIV clinic at Hospital National Simão Mendes, during June 2005 - December 2013 in a retrospective cohort study. Patients were followed until December 2014. LP and AD was defined as a baseline CD4 cell count of 200-349 cells/µL and <200 cells/µL, respectively., Results: A total of 3,720/5,562 (65.7%) patients had a CD4 cell count measured within the first 90 days of HIV diagnosis. Forty-eight percent had AD and 23% had LP. Risk factors for presentation with AD were male sex, age >30 years, Fula and Mandinga ethnicity. HIV-2 and HIV-1/2 dually infected patients had lower risk of AD compared with HIV-1 infected patients. Although antiretroviral therapy (ART) was initiated for 64.4% of patients, those with AD progression had a 3.82 times higher mortality compared to patients with non-LP., Conclusion: The majority of HIV infected patients presented late. Most of the late-presenters had advanced disease and patients with advanced disease had a very high mortality. Initiatives to enroll patients in care at an earlier point are needed and should focus on risk groups., Competing Interests: The authors declare no competing interest.

Background: Better understanding of HIV-2 infection is likely to affect the patient care in areas where HIV-2 is prevalent. In this study, we aimed to characterize the clinical presentations among HIV-1, HIV-2 and HIV-1/2 dual seropositive patients., Methods: In a cross-sectional study, newly diagnosed HIV patients attending the HIV outpatient clinic at Hospital Nacional Simão Mendes in Guinea-Bissau were enrolled. Demographical and clinical data were collected and compared between HIV-1, HIV-2 and HIV-1/2 dual seropositive patients., Results: A total of 169 patients (76% HIV-1, 17% HIV-2 and 6% HIV 1/2) were included in the study between 21 March 2012 and 14 December 2012. HIV-1 seropositive patients were younger than HIV-2 and HIV-1/2 seropositive patients, but no difference in sex was observed. Patients with HIV-1 and HIV-1/2 had a lower baseline CD4 cell count than HIV-2 seropositive patients (median CD4 cell count 185, 198 and 404 cells/μl, respectively (p value 0.001 and 0.05). HIV-1 seropositive patients had a lower BMI and a higher prevalence of weight loss, skin rash and productive cough than HIV-2 seropositive patients (p value 0.03, 0.002, 0.03 and 0.04). Only four cases (2%) of pulmonary tuberculosis (TB) were diagnosed. One patient (1/96, 1%) was tested positive for cryptococcal antigen., Conclusion: HIV-1 and HIV-1/2 seropositive patients have lower CD4 cell counts than HIV-2 seropositive patients when diagnosed with HIV with only minor clinical and demographic differences among groups. Few patients were diagnosed with TB and cryptococcal disease was not found to be a major opportunistic infection among newly diagnosed HIV patients.

The course of disease among HIV-2, HIV-1, and HIV-1/2 dually infected patients is different. We investigated the macrophage activation marker soluble CD163 (sCD163) dynamics in 212 HIV-1, HIV-2, and HIV-1/2 dually infected patients. There were no differences in sCD163 levels at baseline or during follow-up without antiretroviral therapy (ART). At follow-up on ART, median sCD163 levels were decreased for HIV-1-infected patients (P < 0.001), but not among HIV-2 (P = 0.093) or HIV-1/2 dually infected patients (P = 0.145). The larger decrease in sCD163 levels among HIV-1-infected patients during ART may indicate an HIV type-dependent differential effect of ART on macrophage activation during HIV infection.

The development of therapeutic and prophylactic HIV vaccines for African countries is urgently needed, but the question of what immunogens to use needs to be answered. One approach is to include HIV envelope immunogens derived from HIV-positive individuals from a geographically concentrated epidemic with more limited viral genetic diversity for a region-based vaccine. To address if there is a basis for a regional selected antibody vaccine, we have screened two regionally separate cohorts from Guinea-Bissau and Denmark for neutralizing antibody activity and antibody-dependent cellular cytotoxicity (ADCC) against local and nonlocal circulating HIV-1 strains. The neutralizing activity did not demonstrate higher potential against local circulating strains according to geography and subtype determination, but the plasma from Danish individuals demonstrated significantly higher inhibitory activity than that from Guinea-Bissau individuals against both local and nonlocal virus strains. Interestingly, an opposite pattern was observed with ADCC activity, where Guinea-Bissau individual plasma demonstrated higher activity than Danish plasma and was specifically against the local circulating subtype. Thus, on basis of samples from these two cohorts, no local-specific neutralizing activity was detected, but a local ADCC response was identified in the Guinea-Bissau samples, suggesting potential use of regional immunogens for an ADCC-inducing vaccine.

Background: The prevalence of diabetes mellitus (DM) is expected to increase in sub-Saharan Africa. Patients with HIV are at particular risk. We investigated the DM burden among antiretroviral therapy (ART)-naïve patients with HIV in Guinea-Bissau., Methods: Patients were consecutively included. Demographic and lifestyle data were collected and one fasting blood glucose (FBG) measurement was used to diagnose DM (FBG≥7.0 mmol/L) and impaired fasting glucose (IFG) (FBG≥6.1 and <7.0 mmol/L)., Results: By June 2015, 953 newly diagnosed ART-naïve patients with HIV had been included in the study of whom 893 (93.7%) were fasting at the time of inclusion. Median age among the fasting patients was 37 years (IQR 30-46 years) and 562 (62.9%) were women. The prevalence of DM was 5.8% (52/893) while 5.6% (50/893) had IFG. DM was associated with family history of DM (OR 3.92, 95% CI 1.78 to 8.63), being 41-50 years (OR 2.98, 95% CI 1.18 to 7.49) or older than 50 years (OR 3.14, 95% CI 1.09 to 9.07) and Fula ethnicity (OR 2.72, 95% CI 1.12 to 6.62)., Conclusions: DM prevalence was higher among younger patients compared with the background population in Bissau. Traditional risk factors for DM such as advancing age and a family history of DM apply also for ART-naïve patients with HIV., (© The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Several studies have reported conflicting effects of sex on HIV-1 infection. We describe differences in baseline characteristics and assess the impact of sex on HIV progression among patients at a clinic with many HIV-2 and HIV-1/2 dually infected patients., Methods: This study utilised a retrospective cohort of treatment-naïve adults at the largest HIV clinic in Guinea-Bissau from 6 June 2005 to 1 December 2013. Baseline characteristics were assessed and the patients followed until death, transfer, loss to follow-up, or 1 June 2014. We estimated the time from the first clinic visit until initiation of ART, death or loss to follow-up using Cox proportional hazard models., Results: A total of 5694 patients were included in the study, 3702 women (65%) and 1992 men (35%). Women were more likely than men to be infected with HIV-2 (19% vs. 15%, P < 0.01) or dually infected with HIV-1/2 (11% vs. 9%, P = 0.02). For all HIV types, women were younger (median 35 vs. 40 years), less likely to have schooling (55% vs. 77%) or to be married (46% vs. 67%), and had higher baseline CD4 cell counts (median 214 vs. 178 cells/μl). Men had a higher age-adjusted mortality rate (hazard rate ratio (HRR) 1.29, 95% confidence interval (CI) 1.09-1.52) and were more often lost to follow-up (HRR 1.27, 95% CI 1.17-1.39)., Conclusion: Significant differences exist between HIV-infected men and women regardless of HIV type. Men seek treatment at a later stage and, despite better socio-economic status, have higher mortality and loss to follow-up than women., (© 2015 John Wiley & Sons Ltd.)

Introduction: With more people receiving antiretroviral treatment (ART), the need to detect treatment failure and switch to second-line ART has also increased. We assessed CD4 cell counts (as a marker of treatment failure), determined the rate of switching to second-line treatment and evaluated mortality related to treatment failure among HIV-infected patients in Guinea-Bissau., Methods: In this retrospective cohort study, adult patients infected with HIV-1 receiving ≥6 months of ART at an HIV clinic in Bissau were included from June 2005 to July 2014 and followed until January 2015. Treatment failure was defined as 1) a fall in CD4 count to baseline (or below) or 2) CD4 levels persistently below 100 cells/µL after ≥6 months of ART. Cox hazard models, with time since six months of ART as the time-varying coefficient, were used to estimate the hazard ratio for death and loss to follow-up., Results: We assessed 1,591 HIV-1-infected patients for immunological treatment failure. Treatment failure could not be determined in 594 patients (37.3%) because of missing CD4 cell counts. Among the remaining 997 patients, 393 (39.4%) experienced failure. Only 39 patients (9.9%) with failure were switched from first- to second-line ART. The overall switching rate was 3.1 per 100 person-years. Mortality rate was higher in patients with than without treatment failure, with adjusted hazard rate ratios (HRRs) 10.0 (95% CI: 0.9-107.8), 7.6 (95% CI: 1.6-35.5) and 3.1 (95% CI: 1.5-6.3) in the first, second and following years, respectively. During the first year of follow-up, patients experiencing treatment failure had a higher risk of being lost to follow-up than patients not experiencing treatment failure (adjusted HRR 4.4; 95% CI: 1.7-11.8)., Conclusions: We found a high rate of treatment failure, an alarmingly high number of patients for whom treatment failure could not be assessed, and a low rate of switching to a second-line therapy. These factors could lead to an increased risk of resistance development and excess mortality.

Background: With the widespread use of antiretroviral treatment (ART) in Africa, the risk of drug resistance has increased. The aim of this study was to evaluate levels of HIV-1 resistance among patients with HIV-1 and HIV-1/2 dual infections, treated with ART, at a large HIV clinic in Guinea-Bissau., Findings: Patients were selected from the Bissau HIV cohort. All patients had HIV-1 or HIV-1/2 dual infection, a CD4 cell count performed before and 3-12 months after starting ART, and a corresponding available plasma sample. We measured viral load in patients with HIV-1 (n = 63) and HIV-1/2 dual (n = 16) infections a median of 184 days after starting ART (IQR: 126-235 days). In patients with virological failure (defined as viral load >1000 copies/ml) and with sufficient plasma available, we performed an HIV-1 genotypic resistance test. Thirty-six patients (46%) had virological failure. The CD4 cell count did not predict treatment failure. Of the 36 patients with virological failure, we performed a resistance test in 15 patients (42%), and nine patients (9/15; 60%) had resistance mutations. The most common mutation was K103N, which confers high-level resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI). No major mutations against protease inhibitors (PI) were found., Conclusions: Our results showed that patients with HIV-1 and HIV-1/2 dual infections in Guinea-Bissau had a high rate of virological failure and rapid development of NNRTI resistance. It remains to be determined whether a more robust, PI-based treatment regimen might benefit this population more than NNRTIs.

As HIV-2 is intrinsically resistant to nonnucleoside reverse transcriptase inhibitors, it is mandatory to discriminate between HIV types before initiating antiretroviral treatment. Guinea-Bissau has the world's highest prevalence of HIV-2 and HIV-1/HIV-2 dually infected individuals. We evaluated 3 rapid tests for discrimination between HIV-1, HIV-2, and dual infections among 219 patients from Guinea-Bissau by comparing with the gold standard (INNO-LIA). Genie III HIV-1/HIV-2 was the best performer with regard to discriminatory capacity (agreement 91.8%), followed by Immunoflow HIV1-HIV2 (agreement 90.9%) and SD Bioline HIV-1/2 3.0 (agreement 84.5%). Our results underscore the need for evaluation of tests in relevant populations before implementation.

We have designed a therapeutic HIV-1 vaccine concept based on peptides together with the adjuvant CAF01. Peptides represented 15 HLA-supertype-restricted subdominant and conserved CD8 T cell epitopes and three CD4 T-helper cell epitopes. In this phase I clinical trial, safety and immunogenicity were assessed in untreated HIV-1-infected individuals in Guinea-Bissau, West Africa. Twenty-three HIV-1-infected individuals were randomized to receive placebo (n=5) or vaccine (n=18). Safety was appraised by clinical follow-up combined with monitoring of biochemistry, hematology, CD4 T cell counts, and HIV-1 viral loads. T cell immunogenicity was monitored longitudinally by interferon (IFN)-γ ELISpot. New vaccine-specific T cell responses were induced in 6/14 vaccinees for whom ELISpot data were valid. CD4 T cell counts and viral loads were stable. The study shows that therapeutic immunization is feasible and safe in Guinea-Bissau and that it is possible to redirect T cell immunity with CAF01-adjuvanted HIV-1 peptide vaccine during untreated HIV-1 infection in some patients. However, relatively few preexisting and vaccine-induced HIV-1 T cell responses to CD8 T cell epitopes were detected against HIV-1 using IFN-γ ELISpot in this chronically infected African population.

The course of disease among HIV-2, HIV-1, and HIV-1/2 dually infected patients is different. We investigated the macrophage activation marker soluble CD163 (sCD163) dynamics in 212 HIV-1, HIV-2, and HIV-1/2 dually infected patients. There were no differ- ences in sCD163 levels at baseline or during follow-up without antiretroviral therapy (ART). At follow-up on ART, median sCD163 levels were decreased for HIV-1--infected patients (P, 0.001), but not among HIV-2 (P = 0.093) or HIV-1/2 dually infected patients (P = 0.145). The larger decrease in sCD163 levels among HIV-1--infected patients during ART may indicate an HIV type--dependent differential effect of ART on macrophage activation during HIV infection. [ABSTRACT FROM AUTHOR]