Intrahost evolution of the HIV-2 capsid correlates with progression to AIDS.

HIV-2 infection will progress to AIDS in most patients without treatment, albeit at approximately half the rate of HIV-1 infection. HIV-2 capsid (p26) amino acid polymorphisms are associated with lower viral loads and enhanced processing of T cell epitopes, which may lead to protective Gag-specific T cell responses common in slower progressors. Lower virus evolutionary rates, and positive selection on conserved residues in HIV-2 env have been associated with slower progression to AIDS. In this study we analysed 369 heterochronous HIV-2 p26 sequences from 12 participants with a median age of 30 years at enrolment. CD4% change over time was used to stratify participants into relative faster and slower progressor groups. We analysed p26 sequence diversity evolution, measured site-specific selection pressures and evolutionary rates, and determined if these evolutionary parameters were associated with progression status. Faster progressors had lower CD4% and faster CD4% decline rates. Median pairwise sequence diversity was higher in faster progressors (5.7x10-3 versus 1.4x10-3 base substitutions per site, P<0.001). p26 evolved under negative selection in both groups (dN/dS=0.12). Median virus evolutionary rates were higher in faster than slower progressors - synonymous rates: 4.6x10-3 vs. 2.3x10-3; and nonsynonymous rates: 6.9x10-4 vs. 2.7x10-4 substitutions/site/year, respectively. Virus evolutionary rates correlated negatively with CD4% change rates (ρ = -0.8, P=0.02), but not CD4% level. The signature amino acid at p26 positions 6, 12 and 119 differed between faster (6A, 12I, 119A) and slower (6G, 12V, 119P) progressors. These amino acid positions clustered near to the TRIM5α/p26 hexamer interface surface. p26 evolutionary rates were associated with progression to AIDS and were mostly driven by synonymous substitutions. Nonsynonymous evolutionary rates were an order of magnitude lower than synonymous rates, with limited amino acid sequence evolution over time within hosts. These results indicate HIV-2 p26 may be an attractive therapeutic target.

Diabetes and pre-diabetes among police officers in Guinea-Bissau

This study has investigated the prevalence of type 2 diabetes among 1119 police officers in Guinea-Bissau.Those with a random blood glucose (RBG) >8.0 mol/l had HbA1c (glycated haemoglobin) testing. Diabetes (HbA1c >6.5%) was present in 4.1%, and pre-diabetes (HbA1c 5.7­6.5%) was present in a further 4.2%. Factors associated with diabetes were age, weight and ethnicity

Sweden, the first country to achieve the Joint United Nations Programme on HIV/AIDS (UNAIDS)/World Health Organization (WHO) 90-90-90 continuum of HIV care targets.

OBJECTIVES: The Joint United Nations Programme on HIV/AIDS (UNAIDS)/World Health Organization (WHO) 90-90-90 goals propose that 90% of all people living with HIV should know their HIV status, 90% of those diagnosed should receive antiretroviral therapy (ART), and 90% of those should have durable viral suppression. We have estimated the continuum of HIV care for the entire HIV-1-infected population in Sweden. METHODS: The Swedish InfCare HIV Cohort Study collects viral loads, CD4 counts, and viral sequences, along with demographic and clinical data, through an electronic clinical decision support system. Almost 100% of those diagnosed with HIV infection are included in the database, corresponding to 6946 diagnosed subjects living with HIV-1 in Sweden by 31 December 2015. RESULTS: Using HIV surveillance data reported to the Public Health Agency of Sweden, it was estimated that 10% of all HIV-infected subjects in Sweden remain undiagnosed. Among all diagnosed patients, 99.8% were linked to care and 97.1% of those remained in care. On 31 December 2015, 6605 of 6946 patients (95.1%) were on ART. A total of 6395 had been on treatment for at least 6 months and 6053 of those (94.7%) had a viral load < 50 HIV-1 RNA copies/mL. CONCLUSIONS: The 2014 UNAIDS/WHO 90-90-90 goals for HIV care means that > 73% of all patients living with HIV should be virologically suppressed by 2020. Sweden has already achieved this target, with 78% suppression, and is the first country reported to meet all the UNAIDS/WHO 90-90-90 goals.

Analytical evaluation of nine serological assays for diagnosis of syphilis.

BACKGROUND: The diagnosis of syphilis is most frequently dependent on antibody detection with serological assays. Assays for both treponemal and non-treponemal antibodies are needed to provide a sensitive and specific diagnosis. For decades, a first screening has been done with non-treponemal assays, followed by treponemal. However, in recent years, following laboratory automation, the reverse sequence screening algorithms have been developed, using a treponemal assay as the initial screening test. OBJECTIVE: To evaluate serological assays for treponemal and non-treponemal antibodies, to use in reverse algorithm screening of syphilis. MATERIAL AND METHODS: Six treponemal assays (one IgM-specific assay), two non-treponemal assays and one novel dual point-of-care (POC) assay for serological diagnosis of syphilis were evaluated. Serum samples from Guinea-Bissau and Sweden were examined, as well as two performance panels and samples from blood donors. Sensitivity and specificity were calculated for each assay, using different assays as gold standard test. RESULTS: The Macro-Vue RPR Card test was the most sensitive non-treponemal test and the TrepSure Anti-Treponema EIA Screen and the SeroDia TP-PA were the most sensitive and specific treponemal assays. Among the automated assays, both the Liaison Treponema Screen and Architect Syphilis TP showed high sensitivity, however, the former had clearly higher specificity. CONCLUSIONS: In resourced settings, where the reverse sequence algorithm is preferred for screening, an automated treponemal immunoassay for initial screening subsequently followed by the TrepSure test or TP-PA assay as a second treponemal assay appear highly effective. Finally, a quantitative highly sensitive non-treponemal assay, e.g. the Macro-Vue RPR Card test, could then be used as a supplementary test to evaluate activity of the syphilis infection.

High prevalence of HIV-1, HIV-2 and other sexually transmitted infections among women attending two sexual health clinics in Bissau, Guinea-Bissau, West Africa.

The objective was to examine the prevalence of HIV-1, HIV-2 and 10 other sexually transmitted infections (STIs), and to explore the relationship between HIV and those STIs in women attending two sexual health clinics in Bissau, Guinea-Bissau. In all, 711 women with urogenital problems were included. Clinical examination was performed and HIV-1, HIV-2, human T-cell lymphotropic virus (HTLV)-1, HTLV-2 and syphilis were diagnosed by serology. Trichomonas vaginalis was examined using wet mount microscopy. Cervical samples (and swabs from visible ulcers, if present) were used for polymerase chain reaction (PCR) diagnosis of Chlamydia trachomatis, Mycoplasma genitalium, Haemophilus ducreyi, herpes simplex virus (HSV)-1 and HSV-2, and culture diagnosis of Neisseria gonorrhoeae. The prevalence of HIV-1, HIV-2, and HIV-1 and HIV-2 (dual infection) was 9.5%, 1.8% and 1.1%, respectively. The prevalence of HTLV-1 was 2.8%, HTLV-2 0%, HSV-1 1.4%, HSV-2 7.7%, T. vaginalis 20.4%, syphilis 1.0%, N. gonorrhoeae 1.3%, H. ducreyi 2.7%, M. genitalium 7.7% and C. trachomatis 12.6%. HIV-1 and/or HIV-2 infection was significantly associated with active HSV-2 and HIV-1 was significantly associated with M. genitalium infection. In conclusion, HIV-1 and HIV-2 prevalence was higher compared with previous studies of pregnant women in Guinea-Bissau. The prevalence of co-infection of HIV and other STIs is high. National evidence-based guidelines for the management of STIs in Guinea-Bissau are essential.

Human immunodeficiency virus (HIV)-2-specific T lymphocyte proliferative responses in HIV-2-infected and in HIV-2-exposed but uninfected individuals in Guinea-Bissau.

Human immunodeficiency virus (HIV)-2-specific T lymphocyte proliferative responses were determined in cultures of peripheral blood mononuclear cells from HIV-2-exposed uninfected individuals, HIV-2-infected individuals and HIV-negative controls in Guinea-Bissau. Increased HIV-2-specific T lymphocyte proliferative responses were detected in both groups compared to HIV-negative controls (healthy HIV-uninfected individuals without known exposure to an HIV-infected person); five out of 29 of the HIV-2-exposed uninfected and half (16 of 32) of the HIV-2-infected individuals had stimulation indexes >2, compared to one out of 49 of the HIV-negative controls (P = 0.003 and P < 0.0001, respectively). The exposed uninfected individuals had reactivity to a HIV-2 V3-peptide corresponding to amino acids 311-326 of the envelope glycoprotein, while the HIV-2-infected people reacted mainly to HIV-2 whole viral lysate. Thus, this study demonstrates a high degree of HIV-2-specific T helper cell activity, as measured by lymphocyte proliferation, in HIV-2-exposed uninfected individuals as well as in HIV-2-infected subjects. These immune responses could be important for resistance to the infection and for the control of established infection and, thus, play a role in the lower transmission and progression of HIV-2 compared to HIV-1.

Antigen-specific beta-chemokine production and CD8 T-cell noncytotoxic antiviral activity in HIV-2-infected individuals.

Human immunodeficiency virus-2 (HIV-2) is less pathogenic than HIV-1, and the disease progression in HIV-2-infected individuals seems to be similar to that seen in HIV-1-infected long-term nonprogressors. Cell-mediated immune responses and the production of noncytotoxic CD8+ T-cell antiviral factors (CAF) and beta-chemokines have been correlated to protection against HIV-1 and associated with asymptomatic infection and slower disease progression. We investigated the antigen-induced beta-chemokine production in HIV-2-infected patients living in Sweden and in Guinea-Bissau. We also compared in vitro CD8+ T-cell-mediated noncytotoxic antiviral activity against beta-chemokine-sensitive R5 virus (HIV-1Bal) and beta-chemokine-insensitive X4 virus (HIV-1IIIB) in HIV-2-infected patients with that in HIV-1-infected patients. HIV-2-specific beta-chemokine production was demonstrated in a majority of the HIV-2-infected subjects. CD8+ T cells of both HIV-1 and HIV-2-infected individuals suppressed R5 virus replication in vitro in a similar manner, while the inhibition of X4 virus replication seemed to be more frequent and of a higher magnitude among HIV-2-infected patients compared to HIV-1-infected subjects. Taken together, our results indicate that the production of CD8+ T-cell noncytotoxic antiviral factors may contribute to the low transmission of the virus and slower disease progression in HIV-2-infected patients.

Intestinal parasites in HIV-2 associated AIDS cases with chronic diarrhoea in Guinea-Bissau.

Previous studies from African countries where HIV-1 infection is prevalent have shown that infections with Cryptosporidium parvum, Isospora belli and microsporidia are frequently associated with chronic diarrhoea in AIDS patients. The information about the occurrence of these parasites in HIV-2 associated AIDS cases with chronic diarrhoea is limited. We have performed a study of stool parasites in patients from Guinea-Bissau, the country with the highest prevalence of HIV-2 in the world. Stool specimens from 52 adult patients with chronic diarrhoea of which 37 were HIV-positive and fulfilling the clinical criteria of AIDS (five HIV-1, 28 HIV-2 and four dually infected with HIV-1 and HIV-2) were screened for parasitic infections. Twenty five percent of the HIV-2 positive patients were infected with C. parvum, 11% with I. belli and 11% with microsporidia, all three parasites were seen only in HIV-positive patients. The three patients with microsporidiosis, all HIV-2 infected, are to our knowledge the first cases reported from Guinea-Bissau. Other stool parasites such as Blastocystis hominis, hookworm and Strongyloides stercoralis were observed both among HIV-positive and HIV-negative patients.

High mortality and severe immunosuppression in hospitalized patients with pulmonary tuberculosis and HIV-2 infection in Guinea-Bissau.

The aim of this study was to prospectively compare the clinical outcomes in HIV-2-infected and HIV-negative patients with culture-confirmed pulmonary tuberculosis, evaluate immunological changes and investigate risk factors for decreased survival in HIV-2-positive subjects. From 1994 to 1997, 127 consecutive patients with pulmonary tuberculosis were included at the Raoul Follereau Hospital in Bissau, the capital of Guinea-Bissau. All subjects were initially hospitalized, and then followed to the end of the 8-month treatment period. CD4 T-lymphocyte counts were determined by flow cytometry before, during and at the end of the treatment period. The prevalences of HIV-1, HIV-2 and HIV-1/HIV-2 dual reactivity were 8.7%, 23.6% and 9.4%, respectively (95% confidence intervals 3.8-13.6, 16.2-31.0 and 4.4-14.5, respectively). The mortality rate during the study period was significantly higher in HIV-2-positive (p < 0.01) and HIV-1/HIV-2 dually reactive (p < 0.01) patients than in HIV-negative individuals (52.9, 83.3 and 8.7 per 100 person-years, respectively). In HIV-1-positive patients the mortality rate was 30.8/100 person-years (p = NS). Baseline total CD4 cell counts were 213, 104, 235 and 624 x 10(6)/l (% CD4 = 17, 15, 20 and 40) among HIV-1-, HIV-2- and HIV-1/HIV-2-positive and HIV-negative subjects, respectively. The median rates of change per year of total CD4 cell counts in HIV-2-positive and HIV-negative subjects were 66 and 340 x 10(6)/l, respectively (interquartile ranges -78-249 and 21-624). In conclusion, we found a significantly higher mortality rate in HIV-2-positive compared to HIV-negative individuals. Baseline CD4 cell counts were markedly suppressed and similar in all 3 HIV-positive groups, and in a multivariate logistic regression analysis a value of CD4 percentage of < 10 was shown to be an independent predictor of decreased survival in HIV-2-infected subjects.

Plasma viral load in HIV-1 and HIV-2 singly and dually infected individuals in Guinea-Bissau, West Africa: significantly lower plasma virus set point in HIV-2 infection than in HIV-1 infection.

BACKGROUND: The intriguing differences in the natural course, transmissibility, and epidemiological characteristics of human immunodeficiency virus type 1 (HIV-1) and HIV-2 are still insufficiently explained. Differences in plasma viral load are an obvious possibility, but this has been difficult to investigate because of the lack of tests for HIV-2 RNA. OBJECTIVE: To compare plasma HIV RNA load between individuals infected with HIV-1 and HIV-2 in Guinea-Bissau, a West African country with high prevalence and incidence of HIV-1 and HIV-2 infection. METHODS: A total of 102 participants were recruited from ongoing prospective cohort studies. These included 19 HIV-1 and 29 HIV-2 seroincident cases tested at a median of less than 2 years after seroconversion as well as seroprevalent cases with single (9 HIV-1 cases and 31 HIV-2 cases) or dual (n = 14) infections. Plasma HIV RNA levels were determined by a commercial HIV-1 assay and an experimental HIV-2 assay based on the same principles. RESULTS: The viral set point, ie, the semi-equilibrium reached after seronconversion, was 28-fold lower in recent HIV-2 seroconverters than in recent HIV-1 seroconverters (median, 2500 and 70,000 RNA copies per milliliter, respectively; P<. 001). This difference appeared to persist to symptomatic stages of the diseases. Dually infected individuals had lower plasma HIV-1 RNA levels than singly infected individuals. CONCLUSIONS: The differences between HIV-1 and HIV-2 infection are likely to be caused by differences in plasma viral set point and load, but the mechanisms through which HIV-2 infection is contained to a higher degree than HIV-1 remain to be identified. Arch Intern Med. 2000;160:3286-3293.

Molecular characterization of human immunodeficiency virus (HIV)-1 and -2 in individuals from guinea-bissau with single or dual infections: predominance of a distinct HIV-1 subtype A/G recombinant in West Africa.

Guinea-Bissau in West Africa has the highest prevalence of human immunodeficiency virus (HIV)-2 infection in the world, but recently the HIV-1 prevalence increased rapidly with the subsequent appearance of HIV-1 and HIV-2 dual infections. Information about the genetic subtypes of HIV in the region is limited. Therefore, we characterized the env V3 region of HIV-1 and HIV-2 variants through direct DNA sequencing of peripheral blood mononuclear cell samples from 18 individuals with HIV-1 only and 9 individuals with dual infection. Phylogenetic analyses of these new sequences and database sequences from other West African countries showed that all HIV-1 and HIV-2 sequences from singly as well as dually infected individuals, except one, clustered among HIV-1 subtype A and HIV-2 subtype A, respectively. Importantly, a majority of the HIV-1 sequences from Guinea-Bissau and neighbouring countries were closely related with the isolates IbNG, DJ263, and DJ264, which share a common subtype A/G recombination pattern. Analysis of pol gene sequences from selected HIV-1 variants showed that "IbNG-like" viruses in Guinea-Bissau are also recombinant, indicating that the HIV-1 epidemic in Guinea-Bissau and neighbouring countries is dominated by an epidemic spread of a distinct subtype A/G recombinant, which is strikingly similar to the epidemic spread of a subtype A/E recombinant in Southeast Asia. Furthermore, the HIV-1 and HIV-2 variants carried by individuals with dual infection were intermixed with variants from singly infected individuals, indicating that variants involved in dual and single infections have common epidemiological histories.

Trends and interaction of HIV-1 and HIV-2 in Guinea-Bissau, west Africa: no protection of HIV-2 against HIV-1 infection.

OBJECTIVES: To study trends in the prevalence and incidence of HIV-1 and HIV-2 infections in Guinea-Bissau over the last 7 years, and to evaluate the protective effect of HIV-2 against HIV-1 infection. DESIGN: Prospective follow-up of a cohort of police officers in Guinea-Bissau, and sentinel surveillance of pregnant women in Bissau. METHODS: Participants in the police cohort were tested regularly for antibodies to HIV and Treponema pallidum, and information about sexual risk behaviour and a history of sexually transmitted diseases was obtained. Simultaneously, pregnant women at the maternity wards at the National Hospital in Bissau were screened annually for HIV antibodies. To evaluate changes in prevalence and incidence of HIV in the police cohort, the study period was divided into three time strata with 2-3 years in each stratum. For the evaluation of a protective effect of HIV-2 on subsequent HIV-1 infection, two multivariate Poisson regression models were constructed, adjusting for different selected confounding variables. RESULTS: Between 1990 and 1997, 2637 police officers were included in the cohort study, 90.7% of whom were male. The overall prevalence of HIV-1 was 0.9%, of HIV-2 it was 9.7% and of HIV-1 and HIV-2 dual reactivity it was 0.5%. For pregnant women the prevalence rates were 0.9, 5.5 and 0.2% for HIV-1, HIV-2 and dual reactivity respectively. The prevalence of HIV-1 increased significantly whereas the prevalence of HIV-2 declined significantly during the study period, among both police officers and pregnant women. The total incidence of HIV-1 and HIV-2 was 0.74 and 0.83 per 100 person-years respectively in the police cohort. The incidence of HIV-1 increased slightly from 0.62 to 0.78 per 100 person-years (not significant), whereas the incidence of HIV-2 declined significantly from 0.90 to 0.35 per 100 person-years over the study period. Seven police officers seroconverted from HIV-2 to dual reactivity (1.22 per 100 person-years). The adjusted incidence ratio of acquiring HIV-1 infection among HIV-2-positive subjects compared with HIV-negative subjects was 1.65 [95% confidence interval (CI), 0.73-3.74] and 1.98 (95% CI, 0.80-4.87), depending on the confounding variables included. CONCLUSIONS: Our study shows an increasing prevalence of HIV-1 and a decreasing prevalence of HIV-2 in Guinea-Bissau. The incidence of HIV-2 declined significantly whereas the incidence of HIV-1 was relatively stable over the study period. No protective effect of HIV-2 against subsequent HIV-1 infection was observed, instead HIV-2-positive subjects had a tendency towards higher risk of acquiring HIV-1 infection compared with seronegative subjects.

[Reduced frequency of resistant pneumococci in Southern Sweden. Community based disease control projects to minimize antibiotic resistance]. / Sänkt frekvens resistenta pneumokocker i Sydsverige. Samhällsbaserat smittskyddsprojekt mot antibiotikaresistens.

In an attempt to limit the spread of penicillin non-susceptible pneumococci (PNSP) in southern Sweden, early in 1995 an intervention project was launched, using a combination of traditional communicable disease control measures and actions aimed at reducing antibiotics consumption. Patients carrying PNSP (penicillin G MIC (0.5 mg/L) are monitored with nasopharyngeal cultures until PNSP-negative. Pre-school children are kept home from group day-care facilities. Previous antibiotic consumption was identified as a risk factor for PNSP carriage. Antibiotics sales decreased during the study period, and epidemiological findings suggest the dissemination of PNSP in the area to have been reduced by the intervention project.

Child survival in children born to HIV-2 infected women in Guinea-Bissau, West Africa.

We have retrospectively studied the effect of maternal HIV-2 infection and other risk factors on child survival at a family planning centre in Bissau, Guinea-Bissau. A total of 2109 women were included, and the seroprevalence of HIV-2 was 5.7%. Overall child mortality of all live births (n=5912) reported by the women (standardized for age of the mother) was slightly higher among children of HIV-2 seropositive mothers (16.3%) compared with children of HIV seronegative women (14.6%) (not significant). There was a significant association between low level of maternal education and increased child mortality, but no difference in the level of education was found between HIV-2 seropositive and seronegative women.

Clinical features, immunological changes and mortality in a cohort of HIV-2-infected individuals in Bissau, Guinea-Bissau.

Clinical symptoms and immunological changes associated with HIV-2 infection were studied in a cohort of police officers in Guinea-Bissau. HIV-related symptoms were classified according to the WHO clinical staging system. The inclusion period was from January 1990 to January 1997, and among 2637 subjects included (90.7%M, 9.3%F), the prevalence of HIV-1, HIV-2 and dual reactivity to both HIV-1 and HIV-2 was 0.9%, 9.7% and 0.5%, respectively. Weight loss > 10%, diarrhoea or fever > 1 month, generalized lymphadenopathy and generalized pruritic dermatitis were significantly associated with HIV-2 infection as well as suppression of CD4 cells as compared with HIV-negative controls. Females had significantly higher CD4 cell counts than males, both among HIV-negative and HIV-2-positive asymptomatic individuals. The mortality rates/100 person-years (p.y.) were 0.4 in HIV-negative and 2.6 in HIV-2-positive subjects, giving an age-adjusted mortality rate ratio of 6.6 (95% CI, 4.0-10.9; p < 0.001). The mortality rate among HIV-2-infected individuals varied considerably in different stages of the WHO clinical staging system; 1.7 and 8.0/100 p.y. in stage 1 and 3, respectively.

Field evaluation of alternative testing strategies for diagnosis and differentiation of HIV-1 and HIV-2 infections in an HIV-1 and HIV-2-prevalent area.

OBJECTIVE: To identify cost-efficient alternative antibody testing strategies for screening, confirmation and discrimination of HIV-1 and HIV-2 infections, including rapid simple tests (RST) as well as enzyme-linked immunosorbent assays (ELISA), in a HIV-1 and HIV-2-prevalent area. DESIGN: Evaluation and comparison of anti-HIV-1/2 assays, adhering to the World Health Organization recommendations for alternative confirmatory strategies, using banked and prospectively collected specimens in Guinea-Bissau. METHODS: A total of 1110 consecutive sera from Bissau were included in the first phase, of which 198 (17.8%) were HIV-seropositive: 52 (4.7%) HIV-1, 120 (10.8%) HIV-2, and 26 (2.3%) HIV-1/HIV-2 dually reactive. In addition, 95 selected HIV-positive specimens were included for study of sensitivity and cross-reactivity between HIV-1 and HIV-2. Western blot was used as a gold standard for confirming the reactivity of the specimens. All specimens were screened by two assays. Enzygnost ELISA and Capillus RST. Samples reactive by any of the screening assays were further tested by assays chosen for confirmation: UBI ELISA, Innotest ELISA Recombigen RST, Multispot RST and Immunocomb RST. The confirmatory RST as well as Wellcozyme Recombinant HIV-1 ELISA, PEPTI-LAV and INNO-LIA were also used to study differentiation between HIV-1 and HIV-2. RESULTS: The sensitivities of all assays were 100%. The specificities of the screening assays at initial and repeated testing were 98.0 and 99.7%, respectively, for Enzygnost and 99.8 and 99.9%, respectively, for Capillus. The various combinations of two or three assays showed specificities of 99.2-100%. Several possible combinations of assays were identified where a specificity of 100% and good differentiation between HIV-1 and HIV-2 was achieved. Significant differences in the capacity to discriminate were noted; Immunocomb and PEPTI-LAV had the lowest number of dual-reactive results. A follow-up study of 1501 consecutive samples tested with the strategy chosen for routine use showed a sensitivity and specificity comparable to ELISA and Western blot. CONCLUSION: High sensitivities and specificities were obtained with various combinations of assays including RST as well as ELISA, and these procedures are well suited for field use in Africa. Serodiagnostic strategies for HIV can be based on RST alone and differentiation between HIV-1 and HIV-2 can be achieved as part of these strategies. Large differences in the capacity of individual assays to discriminate between HIV-1 and HIV-2 were observed.

PIP: Western blot (WB) is the most widely used serological confirmatory test of ELISA and rapid simple tests (RST) to detect infection with HIV. WB tests, however, are expensive, time-consuming, and have technical disadvantages. The authors therefore conducted a study to identify cost-efficient alternative strategies for HIV-antibody screening, confirmation, and discrimination of HIV-1 and HIV-2 infections in a HIV-1 and HIV-2 prevalent area. 1110 consecutively collected blood sera from Guinea-Bissau were included in the first phase of the study, of which 198 (17.8%) were known to be HIV-seropositive; 52 with HIV-1, 120 with HIV-2, and 26 being HIV-1/HIV-2 dually reactive. 95 selected HIV-positive specimens were included for study of sensitivity and cross-reactivity between HIV-1 and HIV-2, with WB used to confirm specimen reactivity. All specimens were screened by Enzygnost ELISA and Capillus RST, with reactive samples further tested by the following assays for confirmation: UBI ELISA, Innotest ELISA, Recombigen RST, Multispot RST, and Immunocomb RST. The confirmatory RST, Wellcozyme Recombinant HIV-1 ELISA, PEPTI-LAV, and INNO-LIA were also used to study differentiation between HIV-1 and HIV-2. All assays were 100% sensitive. The specificities of the screening assays at initial and repeated testing were 98.0% and 99.7%, respectively, for Enzygnost and 99.8% and 99.9%, respectively, for Capillus. Various combinations of 2-3 assays yielded specificities of 99.2-100%. Screening with Enzygnost ELISA and confirmation and differentiation between HIV-1 and HIV-2 with Capillus RST and Multispot RST was adopted for routine use at Guinea-Bissau's National Public Health Laboratory. A field trial of the approach conducted in 1996 involving 1501 sera found a sensitivity and specificity comparable to ELISA and WB.

HIV-2 genetic variation and DNA load in asymptomatic carriers and AIDS cases in Guinea-Bissau.

The purpose of this study was to document which genetic subtypes of HIV-2 are present in Guinea-Bissau and to investigate whether asymptomatic HIV-2 carriers and AIDS patients carry distinct genetic variants. A secondary aim was to correlate proviral DNA load to clinical and immunologic status of the patients. Thirty-eight asymptomatic HIV-2 carriers and 11 AIDS patients from Bissau, Guinea-Bissau were included in a cross-sectional study in which HIV-2 env V3 sequences, HIV-2 DNA load, and CD4-positive (CD4+) lymphocyte counts were determined. Phylogenetic analyses showed that all investigated subjects carried subtype A HIV-2 variants and that the sequences from AIDS patients and asymptomatic carriers did not form distinct subclusters in the tree. As expected, patients with AIDS had significantly higher median HIV-2 DNA load than did asymptomatic carriers (4.6 vs. 2.0 log10 HIV-2 DNA copies/10(6) CD4+ lymphocytes). Our study indicates that the HIV-2 epidemic in Guinea-Bissau is almost exclusively caused by subtype A HIV-2 variants and that the HIV-2 infections among the asymptomatic carriers and AIDS cases included in the study do not have distinct epidemiologic histories.

PIP: HIV-2 is associated with AIDS but is less pathogenic than HIV-1. HIV-2 is endemic in West Africa, with the highest prevalence in Guinea-Bissau; epidemiologic studies in the country have found HIV-2 seroprevalence in the general population to be 8-10%. HIV-2 seroprevalence increases with age and peaks near age 50-59 years, although the mean age of HIV-2-associated AIDS cases is near 40 years. Only scattered cases of HIV-2 have been reported outside of West Africa, with some concentration in Portugal, France, and India. 38 asymptomatic HIV-2 carriers and 11 AIDS patients from Bissau were included in a cross-sectional study in which HIV-2 env V3 sequences, HIV-2 DNA load, and CD4-positive lymphocyte counts were determined. Phylogenetic analyses showed that all investigated subjects carried subtype A HIV-2 variants and that the sequences from AIDS patients and asymptomatic carriers did not form distinct subclusters in the tree. Subjects with AIDS had significantly higher median HIV-2 DNA load than did asymptomatic carriers.

Increased prevalence of HIV-2 infection in hospitalized patients with severe bacterial diseases in Guinea-Bissau.

We studied the association between HIV-2 infection and bacterial pneumonia, sepsis or pyomyositis, as well as the influence of HIV-2 infection on the clinical outcome in patients with these bacterial infections. A total of 201 consecutive hospitalized patients were included at the Simao Mendes National Hospital in Bissau, Guinea-Bissau. Age- and sex-matched controls were selected from an ongoing census in a semi-urban area of Bissau. Among 201 cases with such bacterial infection the prevalence of HIV-1 was 5.4%, HIV-2, 27.9%, and both HIV-1 and HIV-2 reactivity 6.4%. Among controls, the corresponding prevalence rates were significantly lower, 1.5%, 9.0% and 1.0%, respectively. A total of 140, 31 and 30 cases of pneumonia, sepsis and pyomyositis were included, and the differences in prevalence of HIV-2 compared with the controls also remained significant for each diagnosis separately. Lymphocyte subsets were determined in 93 consecutive patients, and the CD4 cell counts and CD4/CD8 lymphocyte ratios were markedly suppressed in the HIV-2-seropositive group. Due to excess mortality in the seropositive groups with sepsis (75.0%) and pyomyositis (25.0%), the mortality during hospitalization was significantly higher among HIV-2 infected compared to HIV-negative patients. Among cases of pneumonia the mortality was low in the HIV-2-seropositive (2.9%) as well as in the HIV-seronegative (3.4%) group.

PIP: The association between HIV-2 infection and bacterial pneumonia, sepsis, and pyomyositis was examined in 201 consecutive patients hospitalized at Simao Mendes National Hospital in Bissau, Guinea-Bissau with such bacterial diseases and 201 age- and sex-matched controls drawn from a census in a semi-urban area of Bissau. Among cases, HIV-1 prevalence was 5.4%, HIV-2 prevalence was 27.9%, and combined HIV-1 and HIV-2 prevalence was 6.4%. Among controls, these prevalences were 1.5%, 9.0%, and 1.0%, respectively. The prevalence of HIV-2 infection was 25.0% among cases with pneumonia (n = 140), 38.7% among those with sepsis (n = 31), and 30.0% among those with pyomyositis (n = 30). Among the 93 cases for whom T lymphocytes were determined, the absolute number and percentage of CD4 cells and the CD4/CD8 cell ratios were markedly suppressed in the HIV-2-positive group, especially in those with sepsis. Of the 194 patients available for follow-up, 160 were classified as cured or improved, 10 did not improve, and 24 died. Mortality from sepsis and pyomyositis was significantly greater among HIV-2-infected cases than HIV-negative patients. The median percentage of CD4 cells was significantly lower among HIV-2-positive patients who died (9.0%) than survivors (16.5%). These findings confirm the existence of a significant association between HIV-2 and severe bacterial infections as well as a significantly higher mortality during hospitalization from sepsis and pyomyositis in HIV-2-positive patients compared to HIV-negative patients.