The HIV care continuum of Guinea-Bissau; Progress towards the UNAIDS 90-90-90 targets for HIV-1 and HIV-2.

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.

Hepatitis B and C in the adult population of Bissau, Guinea-Bissau: a cross-sectional survey.

OBJECTIVE: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are prevalent in West Africa. To address the WHO 2030 goals of a 90% reduction in incidence and a 65% reduction in mortality for both infections, we assessed the prevalence of HBV and HCV from surveys in the general population. METHODS: Participants in this cross-sectional survey were included from randomly selected houses in a demographic surveillance site in Bissau, Guinea-Bissau. Participants were interviewed and had a blood sample drawn for viral analyses (HBsAg, anti-HBs, anti-HBc, anti-HCV and HCV RNA). Risk factors of HBV and HCV infection were determined by binomial regression adjusted for sex and age. RESULTS: A total of 2715 participants were included in this study. The overall HBsAg prevalence was 18.7% (95% CI: 17.3-20.2%). HBsAg was associated with male sex (adjusted risk ratio (aRR): 1.64), and prevalence decreased with age >34 years. HBV exposure was found in 91.9% of participants. Although 72.6% of individuals without sexual debut had been exposed to HBV, ever engaging in a sexual relationship was associated with higher risk of HBV exposure (aRR 1.18). The anti-HCV prevalence was 0.5% (95% CI: 0.3-0.9%), and 78.6% of those had detectable HCV RNA. Risk factors for anti-HCV sero-positivity were age above 55 (aRR 10.60), a history of blood transfusion (aRR 5.07) and being in a polygamous marriage (aRR 3.52). CONCLUSION: In Guinea-Bissau initiatives to implement treatment and widespread testing are needed to reach the WHO 2030 goals.

OBJECTIF: Le virus de l'hépatite B (VHB) et le virus de l'hépatite C (VHC) sont répandus en Afrique de l'Ouest. Pour atteindre les objectifs de 2030 de l'OMS d'une réduction de 90% de l'incidence et de 65% de la mortalité pour les deux infections, nous avons évalué la prévalence du VHB et du VHC à partir d'enquêtes dans la population générale. MÉTHODES: Les participants inclus dans cette enquête transversale provenaient de foyers sélectionnés au hasard dans un site de surveillance démographique à Bissau, en Guinée-Bissau. Les participants ont été interrogés et ont subi un prélèvement d'échantillon de sang pour des analyses virales (HBsAg, anti-HBs, anti-HBc, anti-HCV et ARN du HCV). Les facteurs de risque d'infection par le VHB et le VHC ont été déterminés par la régression binomiale ajustée en fonction du sexe et de l'âge. RÉSULTATS: 2.715 participants ont été inclus dans cette étude. La prévalence globale de l'HBsAg était de 18,7% (IC95%: 17,3-20,2%). L'HBsAg était associé au sexe masculin (rapport de risque ajusté (aRR): 1,64), et la prévalence diminuait avec l'âge >34 ans. Une exposition au VHB a été observée chez 91,9% des participants. Bien que 72,6% des personnes sans début d'activité sexuelle aient été exposées au VHB, le fait de s'engager dans des relations sexuelles était associé à un risque plus élevé d'exposition au VHB (aRR: 1,18). La prévalence d'anti-VHC était de 0,5% (IC95%: 0,3-0,9%) et 78,6% d'entre eux avaient de l'ARN du VHC détectable. Les facteurs de risque de séropositivité anti-VHC étaient l'âge de plus de 55 ans (aRR: 10,60), les antécédents de transfusion sanguine (aRR: 5,07) et le fait d'être dans un mariage polygame (aRR: 3,52). CONCLUSION: En Guinée-Bissau, des initiatives pour mettre en œuvre un traitement et des tests généralisés sont nécessaires pour atteindre les objectifs de l'OMS 2030.

Phase-out of smallpox vaccination and the female/male HIV-1 prevalence ratio: an ecological study from Guinea-Bissau.

OBJECTIVE: In Guinea-Bissau, West Africa, we observed that having a smallpox vaccination scar was associated with lower HIV-1 prevalence, more strongly for women than men. If this represents a causal effect, the female/male HIV-1 prevalence ratio would increase for birth cohorts no longer receiving smallpox vaccination due to the phase-out of this vaccine. DESIGN: An ecological design using HIV surveys and information about smallpox vaccination coverage. SETTING: Urban and rural Guinea-Bissau. PARTICIPANTS: Participants in HIV surveys were grouped into an age group with decreasing smallpox vaccination coverage (15-34 years) and an age group with steady smallpox vaccination coverage (≥35 years). INTERVENTIONS: The exposure of interest was the phase-out of the smallpox vaccine in Guinea-Bissau. PRIMARY AND SECONDARY OUTCOME MEASURES: HIV-1 prevalence. RESULTS: At both sites, the female/male HIV-1 prevalence ratio increased by calendar time for the age group with decreasing smallpox vaccination coverage; the combined female/male HIV-1 prevalence ratio among people aged 15-34 years was 1.00 (95% CI 0.17 to 5.99) in 1987-1990, 1.16 (95% CI 0.69 to 1.93) in 1996-1997, 2.32 (95% CI 1.51 to 3.56) in 2006-2007 (p value for no trend=0.04). There was no increase in the female-to-male HIV-1 prevalence ratio for the age group >35 years with steady smallpox vaccination coverage; 1.93 (95% CI 0.40 to 9.25) in 1987-1990, 1.32 (95% CI 0.83 to 2.10) in 1996-1997, 0.81 (95% CI 0.56 to 1.16) in 2006-2007 (p value for no trend=0.07). CONCLUSIONS: Thus, data was compatible with the deduction that the phase-out of smallpox vaccination may have increased the susceptibility to HIV-1 relatively more for women than men. Hence, phasing out smallpox vaccination may have contributed to the global increase in the female/male HIV-1 prevalence ratio among young individuals. Due to the potential fallacies of ecological studies, the results should be interpreted carefully, and this hypothesis needs further assessment. If the hypothesis is true, studies of smallpox vaccination could inform HIV-1 vaccine research.

Discriminatory rapid tests cause HIV-type misclassification-evaluation of three rapid tests using clinical samples from Guinea-Bissau.

BACKGROUND: Discrimination among HIV types is important because HIV-2 is naturally resistant to some of the first-line drugs used in the treatment of HIV-1. We evaluated three assays for HIV-type discriminatory capacity: SD Bioline HIV 1/2 3.0 (Bioline), First Response HIV 1-2-0 Card Test (First Response) and Genie III HIV-1/HIV-2 (Genie III). METHODS: Based on results from the Bioline assay, samples from 239 HIV-infected patients from the Bissau HIV cohort in Guinea-Bissau were retrospectively selected for evaluation. Genie III and First Response were scored by three independent readers and compared with a reference test (INNO-LIA HIV I/II Score) confirmed by HIV RNA as well as DNA detection. RESULTS: The best performing test was Genie III, with an average agreement with the reference test of 93.4%, followed by First Response (86.1%) and Bioline (72.4%). First Response and Bioline were scored with a false high number of HIV-1/2 dual infections. For both First Response and Genie III, there were discrepancies among independent readers, and some tests were scored as HIV non-reactive. CONCLUSIONS: Using these rapid tests with a suboptimal performance will presumably result in a high rate of false HIV-1/2 dual diagnoses, depriving patients of alternative treatment options in cases of treatment failure.

Performance of Bio-Rad HIV-1/2 Confirmatory Assay in HIV-1, HIV-2 and HIV-1/2 dually reactive patients - comparison with INNO-LIA and immunocomb discriminatory assays.

BACKGROUND: Being able to discriminate between HIV-1, HIV-2 and HIV-1/2 dual infection is imperative for the appropriate selection of antiretroviral therapy (ART) in regions with high HIV-2 endemicity. OBJECTIVES: To evaluate Bio-Rad Geenius HIV-1/2 Confirmatory Assay against INNO-LIA HIV 1/2 Score and ImmunoComb HIV 1/2 BiSpot with an emphasis towards ability to discriminate between HIV-1, HIV-2 and HIV-1/2 dual infection. MATERIAL AND METHODS: 131 samples from ART naïve HIV infected patients in Guinea-Bissau were selected retrospectively and tested with Geenius, INNO-LIA and Immunocomb. HIV-1/2 RNA were measured in all samples and HIV-1/2 DNA in 59 samples. RESULTS: The Geenius reader typed 62 samples as HIV-1 reactive, 37 samples as HIV-2 reactive and 32 samples as HIV-1/2 dually reactive. Geenius manual reading classified 10% more samples as HIV-1/2 dually reactive (n = 35). INNO-LIA typed 63 samples as HIV-1 reactive, 36 samples as HIV-2 reactive and 32 samples as HIV-1/2 dually reactive while Immunocomb classified a large proportion of samples as HIV-1/2 dually reactive (n = 45). The measurement of agreement of the Geenius reader compared with INNO-LIA and Immunocomb was 92.4% and 84.0% respectively while the measurement of agreement of Geenius manual reading compared with INNO-LIA and Immuncomb was 93.1% and 89.3% respectively. CONCLUSIONS: Geenius has similar performance characteristics as INNO-LIA, and performs considerably better than Immunocomb, for differentiating between HIV types. This is especially true when using the Geenius reader while manual reading of the Geenius assay seemed to overestimate the numbers of HIV-1/2 dually reactive samples.

HTLV prevalence is no longer following the decreasing HIV prevalence - 20 years of retroviral surveillance in Guinea-Bissau, West Africa.

BACKGROUND: The HIV-2 and HTLV-1 prevalences in Bissau have followed similar trends in surveys from 1996 and 2006 with HTLV-1 prevalences of 3.6% and 2.3%, respectively. However, following the introduction of antiretroviral treatment (ART) and informative campaigns about HIV, the epidemics may have shifted. To evaluate the current HTLV prevalence and the continued association with HIV, we performed a third survey. METHODS: A cross-sectional survey was performed from November 2014 to February 2016. In total, 2583 participants were interviewed, tested for HIV, and had blood samples collected. Samples were analysed for anti-HTLV using chemiluminescence and immunoblot assays. We calculated the HTLV prevalence for 2016 and examined risk factors for HTLV and associations with HIV using binominal regression. RESULTS: The prevalence of HTLV was 2.8% (71/2583), 1.5% (16/1,089) for men and 3.7% (55/1,494) for women. Old age, female sex, HIV-2 infection and sharing a house with a HTLV- infected person were strong risk factors for HTLV. In contrast to previous studies, we found a non-significant increase in prevalence among the 15-24 year-olds since 2006, supporting ongoing transmission. CONCLUSIONS: The HTLV prevalence in Bissau showed a non-significant increase. We found evidence supporting continuous vertical and horizontal routes of transmissions.

Low Postseroconversion CD4+ T-cell Level Is Associated with Faster Disease Progression and Higher Viral Evolutionary Rate in HIV-2 Infection.

A positive correlation between virus evolutionary rate and disease progression has been shown for human immunodeficiency virus type 1 (HIV-1) infection. Much less is known about HIV-2, the second causative agent of AIDS. We analyzed 528 HIV-2 env V1-C3 sequences generated from longitudinal plasma samples that were collected from 16 study participants during a median observation time of 7.9 years (interquartile range [IQR], 5.2 to 14.0 years). Study participants were classified as faster or slower disease progressors based on longitudinal CD4+ T-cell data. The HIV-2 evolutionary rate was significantly associated with CD4+ T-cell levels and was almost twice as high among the faster progressors as among the slower progressors. Higher evolutionary rates were accounted for by both synonymous and nonsynonymous nucleotide substitutions. Moreover, slow disease progression was associated with stronger positive selection on HIV-2/SIVsm (simian immunodeficiency virus infecting sooty mangabey) surface-exposed conserved residues. This study demonstrated a number of previously unknown characteristics linking HIV-2 disease progression with virus evolution. Some of these findings distinguish HIV-2 from HIV-1 and may contribute to the understanding of differences in pathogenesis.IMPORTANCE The relationship between HIV evolution and disease progression is fundamental to our understanding of HIV immune control and vaccine design. There are no clear definitions for faster and slower HIV-2 disease progression and for the relationship of the rate of progression with HIV-2 evolution. To address the hypothesis that viral evolution is correlated with disease progression in HIV-2 infection, we determined faster and slower disease progression based on follow-up data from a prospective cohort of police officers in Guinea-Bissau. The analysis showed that although the CD4+ T-cell level and the decline in the level were independently associated with progression to AIDS, only the CD4+ T-cell level or a combined CD4+ T-cell level/decline stratification was associated with the rate of HIV-2 evolution. The HIV-2 evolutionary rate was almost twice as high among the faster progressors as among the slower progressors. Importantly, this report defines previously unknown characteristics linking HIV-2 disease progression with virus evolution.

Neutralizing Antibody Response and Antibody-Dependent Cellular Cytotoxicity in HIV-1-Infected Individuals from Guinea-Bissau and Denmark.

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.

Cocirculation of several similar but unique HIV-1 recombinant forms in Guinea-Bissau revealed by near full-length genomic sequencing.

The dynamic HIV-1 epidemic has resulted in the emergence of several different subtypes and recombinant forms that may differ in biological properties. A recombinant form of CRF02_AG and subsubtype A3 (A3/02) was recently described based on env sequencing and was associated with faster disease progression rates compared with its parental strains. Here, we performed near full-length sequencing of the A3/02 variant to characterize the recombination patterns of a potential novel and more pathogenic circulating recombinant form of HIV-1 in Guinea-Bissau. HIV-1 proviral DNA was extracted from blood samples of individuals infected with the A3/02 recombinant form. The recombination patterns were investigated for six samples that were successfully amplified and sequenced. We found that all six full-length genomes were recombinant forms composed of CRF02_AG and A3 with a recombination hot-spot in the C2 region of env. However, the recombination patterns in the remaining genome differed between samples. Two samples displayed similar recombination profiles, indicative of a homogeneous recombinant form circulating in the population in Guinea-Bissau, whereas the remaining four samples represented unique recombinant forms. The characterization of five different recombination profiles indicated a high frequency of recombination. The recombination breakpoint in the C2 region was identified as the principal common feature shared between sequences, suggesting that this region may have an impact on disease progression rate. Since novel recombinant forms may have characteristics associated with a higher potential of spread in the human population, this study highlights the importance of continuous screening and surveillance of the HIV-1 epidemic.

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.

Hepatitis B and Delta virus are prevalent but often subclinical co-infections among HIV infected patients in Guinea-Bissau, West Africa: a cross-sectional study.

BACKGROUND: Co-infection with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) may lead to accelerated hepatic disease progression with higher rates of liver cirrhosis and liver-related mortality compared with HBV mono-infection. Co or super-infection with hepatitis Delta virus (HDV) may worsen the liver disease and complicate treatment possibilities. METHODS: In this cross-sectional study we included HIV-infected individuals who had a routine blood analysis performed at an HIV clinic in Bissau, Guinea-Bissau between the 28th of April and 30th of September 2011. All patients were interviewed, had a clinical exam performed and had a blood sample stored. The patients' samples were tested for HBV and HDV serology, and HBV/HDV viral loads were analyzed using in-house real-time PCR methods. RESULTS: In total, 576 patients (417 HIV-1, 104 HIV-2 and 55 HIV-1/2) were included in this study. Ninety-four (16.3%) patients were HBsAg positive of whom 16 (17.0%) were HBeAg positive. In multivariable logistic regression analysis, CD4 cell count <200 cells/µl and animist religion were significantly associated with HBsAg positivity. Due to scarcity of available plasma, virological analyses were not performed for eight patients. HBV DNA was detected in 42 of 86 samples (48.8%) positive for HBsAg and genotyping was performed in 26 patients; 25 of whom had genotype E and one genotype D. Among 9 patients on antiretroviral treatment (ART), one patient had the [L180M, M204V] mutation associated with lamivudine resistance. Among the HBsAg positive patients 25.0% were also positive for anti-HDV and 4/9 (44.4%) had detectable HDV RNA. CONCLUSION: HBV and HDV were frequent co-infections among HIV positive patients in Guinea-Bissau and chronic infection was associated with severe immunosuppression. Lamivudine was widely used among HBsAg positive patients with the risk of developing resistant HBV.

Faster progression to AIDS and AIDS-related death among seroincident individuals infected with recombinant HIV-1 A3/CRF02_AG compared with sub-subtype A3.

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) is divided into subtypes and circulating recombinant forms (CRFs) but the impact of subtype/CRF on disease progression is not fully understood. METHODS: We determined the HIV-1 subtype/CRF of 152 seroincident individuals from Guinea-Bissau, based on the C2-V3 region of env. Disease progression was measured as time from estimated seroconversion to AIDS and AIDS-related death. Hazard ratios (HRs) were calculated using a Cox proportional hazard model, adjusting for gender and age at seroconversion. RESULTS: The major subtypes/CRFs identified were CRF02_AG (53%), A3 (29%), and A3/02 (a recombinant of A3 and CRF02_AG) (13%). Infection with A3/02 was associated with a close to 3-fold increased risk of AIDS and AIDS-related death compared to A3 (HR = 2.6 [P = 0.011] and 2.9 [P = 0.032], respectively). The estimated time from seroconversion to AIDS and AIDS-related death was 5.0 and 8.0 years for A3/02, 6.2 and 9.0 years for CRF02_AG, and 7.2 and 11.3 years for A3. CONCLUSION: Our results show that there are differences in disease progression between HIV-1 A-like subtypes/CRFs. Individuals infected with A3/02 have among the fastest progression rates to AIDS reported to date. Determining the HIV-1 subtype of infected individuals could be important in the management of HIV-1 infections.

Performance of 3 rapid tests for discrimination between HIV-1 and HIV-2 in Guinea-Bissau, West Africa.

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.

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.

Declining prevalence rates of syphilis among police officers in Guinea-Bissau, West Africa, 1990-2010.

We analyzed prevalence rates of syphilis (positive Treponema pallidum hemagglutinin antigen/T. pallidum particle antigen and venereal disease research laboratory test) among police officers in Guinea-Bissau from 1990 to 2010 and found a significant decline from 4.5% to 0.4% (P = 0.0065). Our results are in line with other recent reports from West Africa. More research is needed to identify the reasons for this decline.

Loss to follow-up occurs at all stages in the diagnostic and follow-up period among HIV-infected patients in Guinea-Bissau: a 7-year retrospective cohort study.

OBJECTIVES: To describe loss to follow-up (LTFU) at all stages of the HIV programme. DESIGN: A retrospective cohort study. SETTING: The HIV clinic at Hospital National Simão Mendes in Bissau, Guinea-Bissau. PARTICIPANTS: A total of 4080 HIV-infected patients. OUTCOME MEASURES: Baseline characteristics, percentages and incidence rates of LTFU as well as LTFU risk factors at four different stages: immediately after HIV diagnosis (stage 1), after the first CD4 cell count and before a follow-up consultation (stage 2), after a follow-up consultation for patients not eligible for antiretroviral treatment (ART; stage 3) and LTFU among patients on ART (stage 4). RESULTS: Almost one-third of the patients were lost to the programme before the first consultation where ART initiation is decided; during the 7-year observation period, more than half of the patients had been lost to follow-up (overall incidence rate=51.1 patients lost per 100 person-years). Age below 30 years at inclusion was a risk factor for LTFU at all stages of the HIV programme. The biggest risk factors were body mass index <18.5 kg/m(2) (stage 1), male gender (stage 2), HIV-2 infection (stage 3) and CD4 cell count <200 cells/µL (stage 4). CONCLUSIONS: In this study, LTFU constituted a major problem, and this may apply to other similar ART facilities. More than half of the patients were lost to follow-up shortly after enrolment, possibly implying a high mortality. Thus, retention should be given a high priority.

Sequence analysis of HIV-1 isolates from Guinea-Bissau: selection of vaccine epitopes relevant in both West African and European countries.

For a CD8 epitope-based vaccine to match different geographic locations, the targeted epitopes for cytotoxic T-lymphocytes (CTLs) must be present in the local circulating HIV-1 strains. Secondly, the vaccine epitopes should match the host population HLA types. We characterized two new HIV-1 isolates from Guinea-Bissau. Also, we have identified 15 subdominant CD8 epitopes representing common HLA super-types theoretically covering most HLA alleles in any population. Herein we demonstrate that the selected vaccine epitopes are well conserved and simultaneously present in sequences from West Africa and Denmark. Use of the selected epitopes will likely ensure ≥10 immune targets in the majority of candidates for experimental therapeutic vaccination in both geographic regions. Our results warrant testing of the selected vaccine epitopes in both geographic locations.

Prevalence and incidence of HIV-1 and HIV-2 before, during and after a civil war in an occupational cohort in Guinea-Bissau, West Africa.

OBJECTIVES: To study prevalence and incidence of HIV-1 and HIV-2 between 1990 and 2007 and to examine impact of the civil war in 1998-1999. We also wanted to investigate possible interaction between HIV-1 and HIV-2. DESIGN: Open prospective cohort study of 4592 police officers in Guinea-Bissau, West Africa. METHODS: Analysis of HIV-1 and HIV-2 prevalence and incidence divided in 2-3 years time strata. RESULTS: HIV-1 prevalence (including HIV-1/HIV-2 dual reactivity) increased gradually from 0.6 to 3.6% before the war and was 9.5% in the first serosurvey after the war. HIV-1 incidence more than doubled during and shortly after the war, from 0.50 to 1.22 per 100 person-years. Both prevalence and incidence of HIV-1 decreased in the following periods after the war. HIV-2 prevalence decreased from 13.4 to 6.2% during the entire study period and HIV-2 incidence decreased from 1.38 to 0.18 per 100 person-years. Adjusted incidence rate ratios of HIV-1 incidence in HIV-2-positive participants compared with HIV-negative participants ranged from 1.02 to 1.18 (not significant) depending on the confounding variables included. CONCLUSION: HIV-1 has increased, whereas HIV-2 has decreased and the risk of acquiring HIV-1 is now more than four times higher as compared with HIV-2. The civil war in 1998-1999 appears to have induced a temporary increase in HIV-1 transmission, but now a stabilization of HIV-1 incidence and prevalence seems to have taken place. There was no evidence of a protective effect of HIV-2 against HIV-1 infection.