Life expectancy of HIV-infected patients followed at the largest hospital in Guinea-Bissau is one-fourth of life expectancy of the background population.

PURPOSE: To estimate the life expectancy (LE) of HIV-infected patients in the West African country Guinea-Bissau and compare it with the background population. METHODS: Using data from the largest HIV outpatient clinic at the Hospital Nacional Simão Mendes in the capital Bissau, a retrospective observational cohort study was performed. The study included patients attending the clinic between June 2005 and January 2018. A total of 8958 HIV-infected patients were included. In the analysis of the background population, a total of 109,191 people were included. LE incorporating loss to follow-up (LTFU) was estimated via Kaplan-Meier estimators using observational data on adult HIV-infected patients and background population. RESULTS: The LE of 20-year-old HIV-infected patients was 9.8 years (95% CI 8.3-11.5), corresponding to 22.3% (95% CI 18.5-26.7%) of the LE of the background population. (LE for 20-year-olds in the background population was 44.0 years [95% CI 43.0-44.9].) Patients diagnosed with CD4 cell counts below 200 cells/µL had a LE of 5.7 years (95% CI 3.6-8.2). No increase in LE with later calendar period of diagnosis was observed. CONCLUSIONS: LE was shown to be markedly lower among HIV-infected patients compared with the background population. While other settings have shown marked improvements in prognosis of HIV-infected patients in recent years, no improvement in Bissau was observed over time (9.8 years (95% CI 7.6-12.2) and 9.9 years (95% CI 7.6-12.1) for the periods 2005-2010 and 2014-2016, respectively).

Soluble Macrophage Mannose Receptor (sCD206/sMR) as a Biomarker in Human Immunodeficiency Virus Infection.

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.

Assessing factors for loss to follow-up of HIV infected patients in Guinea-Bissau.

PURPOSE: The objective of this study was to ascertain vital status of patients considered lost to follow-up at an HIV clinic in Guinea-Bissau, and describe reasons for loss to follow-up (LTFU). METHODS: This study was a cross-sectional sample of a prospective cohort, carried out between May 15, 2013, and January 31, 2014. Patients lost to follow-up, who lived within the area of the Bandim Health Project, a demographic surveillance site (DSS), were eligible for inclusion. Active follow-up was attempted by telephone and tracing by a field assistant. Semi-structured interviews were done face to face or by phone by a field assistant and patients were asked why they had not shown up for the scheduled appointment. Patients were included by date of HIV testing and risk factors for LTFU were assessed using Cox proportional hazard model. RESULTS: Among 561 patients (69.5 % HIV-1, 18.0 % HIV-2 and 12.6 % HIV-1/2) living within the DSS, 292 patients had been lost to follow-up and were, therefore, eligible for active follow-up. Vital status was ascertained in 65.9 % of eligible patients and 42.7 % were alive, while 23.2 % had died. Information on reasons for LTFU existed for 103 patients. Major reasons were moving (29.1 %), travelling (17.5 %), and transferring to other clinics (11.7 %). CONCLUSION: A large proportion of the patients at the clinic were lost to follow-up. The main reason for this was found to be the geographic mobility of the population in Guinea-Bissau.

Differential effects of sex in a West African cohort of HIV-1, HIV-2 and HIV-1/2 dually infected patients: men are worse off.

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.

Challenges facing HIV treatment in Guinea-Bissau: the benefits of international research collaborations.

PROBLEM: The introduction of antiretroviral therapy (ART) for HIV infection in sub-Saharan Africa has improved the quality of life of millions of people and reduced mortality. However, substantial problems with the infrastructure for ART delivery remain. APPROACH: Clinicians and researchers at an HIV clinic in Guinea-Bissau identified problems with the delivery of ART by establishing a clinical database and by collaborating with international researchers. LOCAL SETTING: The Bissau HIV cohort study group was established in 2007 as a collaboration between local HIV physicians and international HIV researchers. Patients were recruited from the HIV clinic at the country's main hospital in the capital Bissau. RELEVANT CHANGES: Between 2005 and 2013, 5514 HIV-positive patients were treated at the clinic. Working together, local health-care workers and international researchers identified the main problems affecting ART delivery: inadequate drug supply; loss of patients to follow-up; and inadequate laboratory services. Solutions to these problems were devised. The collaborations encouraged local physicians to start their own research projects to find possible solutions to problems at the clinic. LESSONS LEARNT: The HIV clinic in Bissau faced numerous obstacles in delivering ART at a sufficiently high quality and patients' lives were put in jeopardy. The effectiveness of ART could be enhanced by delivering it as part of an international research collaboration since such collaborations can help identify problems, find solutions and increase the capacity of the health-care system.

HTLV infected individuals have increased B-cell activation and proinflammatory regulatory T-cells.

Human T-lymphotropic virus (HTLV) affects the human immune system in many ways, most notably by inducing proliferation of infected CD4 + T cells, but several other cell types are also affected. To characterize the effects of HTLV infection, we analysed blood samples from HTLV-infected individuals by flow cytometry. Samples were collected from visitors at the HIV clinic in Bissau, Guinea-Bissau. These samples were tested for HTLV and HIV, and 199 were analysed by flow cytometry using panels for B cells, T-cell maturation and activation, regulatory T cells (Tregs) and monocytes. CD80+ cell proportions were significantly higher in HTLV infected than in HTLV uninfected in all B cell subsets. Among T cells, there was no change in cell distribution between maturation stages, but a higher CD25+ proportion among Tregs (61.1 % vs 36.3 %, p < 0.001) in HTLV infected than in HTLV uninfected. The level of CD49d on individual cells was also higher (MFI 2734.5 vs 1,041, p < 0.001). In HTLV infected individuals, CD8 + T cells had a lower proportion of CTLA-4+ (2.5 % vs 3.5 %, 0.048) and higher PD1+ proportion on the CD45RO + subset (81.6 % vs 77.1 %, p < 0.001). Together, these findings point toward reduced regulation in HTLV + patients, which leads to immune activation. This study corroborates previous findings and offers new insight into the effects of HTLV by providing a broad flowcytometric analysis of immune cells in HTLV + individuals.

HIV-1 and HIV-2 prevalence, risk factors and birth outcomes among pregnant women in Bissau, Guinea-Bissau: a retrospective cross-sectional hospital study.

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.

Correction: Political instability and supply-side barriers undermine the potential for high participation in HIV testing for the prevention of mother-to-child transmission in Guinea-Bissau: A retrospective cross-sectional study.

[This corrects the article DOI: 10.1371/journal.pone.0199819.].

Political instability and supply-side barriers undermine the potential for high participation in HIV testing for the prevention of mother-to-child transmission in Guinea-Bissau: A retrospective cross-sectional study.

BACKGROUND: The World Health Organization recommends HIV testing is included in routine screening tests for all pregnant women in order to prevent mother-to-child-transmission of HIV and reduce maternal morbidity and mortality. OBJECTIVES: To assess the proportion of women approached and tested for HIV at delivery and factors associated with non-testing at the maternity ward of the Simão Mendes National Hospital (HNSM) in Bissau, Guinea-Bissau. METHODS: We conducted a retrospective cross-sectional study among women presenting for delivery from June 2008 until May 2013. During the study period, national policy included opt-out HIV-testing at delivery. Modified Poisson regression models were used to examine the association of maternal characteristics with HIV testing. Time trends were determined using Pearson's χ2 test. RESULTS: Seventy-seven percent (24,217/31,443) of women presenting for delivery were counselled regarding PMTCT, of whom 99.6% (24,107/24,217) proceeded with HIV testing. The provision of opt-out HIV testing at labour increased from 38.1% (1,514/3973) in 2008 to 95.7% (2,021/2,113) in 2013, p<0.001. There were four distinct periods (two or more consecutive calendar months) when less than 50% of women delivering at HNSM were tested. Periods of political instability were significantly associated with not testing for HIV (adjusted prevalence ratio [APR] 1.79; 95% CI 1.73-1.84), as was a lower educational status (APR 1.05; 95% CI 1.00-1.10), admission during evenings/nights (APR 1.05; 95% CI 1.01-1.09) and on Sundays (APR 1.14; 95% CI 1.07-1.22) and Mondays (APR 1.12; 95% CI 1.05-1.19). CONCLUSIONS: Rapid scale-up of PMTCT HIV testing services and high testing coverage was possible in this resource-limited setting but suffered from regular interruptions, most likely because of test stock-outs. Establishing proper stock management systems and back-up plans for periods of political instability is required to ensure the maintenance of health system core functions and increase health system resilience.

High prevalence and excess mortality of late presenters among HIV-1, HIV-2 and HIV-1/2 dually infected patients in Guinea-Bissau - a cohort study from West Africa.

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.

Cohort Profile: The Bissau HIV Cohort-a cohort of HIV-1, HIV-2 and co-infected patients.

The West African country Guinea-Bissau is home to the world's highest prevalence of HIV-2, and its HIV-1 prevalence is rising. Other chronic viral infections like human T-lymphotropic virus type 1 (HTLV-1) and hepatitis B virus are common as well. The Bissau HIV Cohort was started in 2007 to gain new insights into the overall effect of introducing antiretroviral treatment in a treatment-naïve population with concomitant infection with three retroviruses (HIV-1, HIV-2 and HTLV-1) and tuberculosis. The cohort includes patients from the HIV clinic at Hospital Nacional Simão Mendes, the main hospital in Bissau, the capital of the country. From July 2007 to June 2013, 3762 HIV-infected patients (69% HIV-1, 18% HIV-2, 11% HIV-1/2 and 2% HIV type unknown) were included in the world's largest single-centre HIV-2 cohort. Demographic and clinical data are collected at baseline and every 6 months, together with CD4 cell count and routine biochemistry analyses. Plasma and cells are stored in a biobank in Denmark. The Bissau HIV Cohort is administered by the Bissau HIV Cohort study group. Potential collaborators are invited to contact the chair of the cohort study group, Christian Wejse, e-mail: [wejse@dadlnet.dk].

Lack of awareness of treatment failure among HIV-1-infected patients in Guinea-Bissau - a retrospective cohort study.

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.

Hepatitis C prevalence among HIV-infected patients in Guinea-Bissau: a descriptive cross-sectional study.

OBJECTIVES: To estimate the prevalence and determine the clinical presentation of risk factors of hepatitis C virus (HCV) among HIV-infected patients in Bissau, Guinea-Bissau. METHODS: In this cross-sectional study, we included individuals who had a routine blood analysis performed during the period April 28 to September 30, 2011. Patient samples were tested for HCV antibodies (anti-HCV) with a chemiluminescence test (Architect, Abbott, USA) and INNO-LIA HCV Score (Innogenetics, Belgium). HCV viral load and genotype were analyzed using an in-house real-time PCR method. RESULTS: In total, 576 patients were included (417 HIV-1, 104 HIV-2, and 55 HIV-1/2). Ten (1.7%) patients were anti-HCV-positive and eight (1.4%) patients had detectable HCV RNA; all were genotype 2. In a multivariable logistic regression analysis, age >50 years was associated with anti-HCV reactivity (p<0.01). No subjective symptoms or objective signs were more prevalent among patients with detectable HCV RNA compared to patients without detectable HCV RNA. Biochemically, detectable HCV RNA was associated with elevated amylase (83.3% vs. 38.6%, p=0.03), but not with the liver enzymes alanine aminotransferase and aspartate aminotransferase. CONCLUSIONS: The prevalence of anti-HCV was low and comparable to similar settings, and genotype analysis confirmed the presence of genotype 2 in West Africa.

Barriers and facilitators to antiretroviral therapy adherence among patients with HIV in Bissau, Guinea-Bissau: A qualitative study.

Adherence is a decisive factor in achieving a successful response to antiretroviral therapy (ART) for HIV infection. No previous studies have been conducted regarding HIV treatment adherence in Guinea-Bissau. In this study we assessed barriers and facilitators to patient ART adherence. Semi-structured interviews were conducted with 20 adult, HIV infected individuals receiving ART at a HIV treatment centre in Bissau, Guinea-Bissau. The grounded theory method was used to gather and analyse data. Results indicated that HIV-related knowledge was a determining factor for optimal adherence. The facilitators were experienced treatment benefits and complementing social networks. The barriers were treatment-related costs and competing livelihood needs; poor clinic infrastructure; perceived stigma; and traditional practices. Our findings indicate that good ART adherence, especially in resource-limited settings, requires that patients achieve adequate HIV-related knowledge. More studies on HIV-related knowledge and adherence among HIV infected individuals are currently needed.

Therapeutic vaccination using cationic liposome-adjuvanted HIV type 1 peptides representing HLA-supertype-restricted subdominant T cell epitopes: safety, immunogenicity, and feasibility in Guinea-Bissau.

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.

Prevalence and risk determinants of HIV-1 and HIV-2 infections in pregnant women in Bissau.

OBJECTIVES: To analyse the risk determinants of HIV-1 and HIV-2 infections in pregnant women in Bissau. METHODS: Pregnant women attending the antenatal clinics of Bissau between January 2002 and June 2006 were consecutively tested unless they opted out. RESULTS: Among 23,869 tested women the overall prevalence of HIV-1 was 5.7%, that of HIV-2 was 2.4%, and these included the 0.7% prevalence of HIV-1 and HIV-2 duals. The main factors associated with the risk of HIV-1 infection were older age, occupation and number of sexual partners. Beafada and Mandinga ethnic groups were at greater risk of presenting HIV-1, and Bijago and Papel at lower risk. The factors associated with the risk of HIV-2 were age, literacy and occupation; the Beafada were at greater risk than the other ethnic groups. CONCLUSIONS: The prevalence of HIV-2 infection decreased overtime, whereas that of HIV-1 infection remained substantially stable, but was higher than that observed in previous studies. The rapid decline in the rates of HIV-2 infection suggests that many of the factors that allowed its exponential growth in the past have now been partially removed, and that sexual and vertical transmission have not been sufficient to maintain and extend the epidemic.