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.

HIV treatment in Guinea-Bissau: room for improvement and time for new treatment options.

Despite advances in the treatment quality of HIV throughout the world, several countries are still facing numerous obstacles in delivering HIV treatment at a sufficiently high quality, putting patients' lives in jeopardy. The aim of this status article is to give an overview of HIV treatment outcomes in the West African country, Guinea-Bissau, and to assess how newer treatment strategies such as long-acting injectable drugs or an HIV cure may limit or stop the HIV epidemic in this politically unstable and low-resource setting. Several HIV cohorts in Guinea-Bissau have been established and are used as platforms for epidemiological, virological, immunological and clinical studies often with a special focus on HIV-2, which is prevalent in the country. The Bandim Health Project, a demographic surveillance site, has performed epidemiological HIV surveys since 1987 among an urban population in the capital Bissau. The Police cohort, an occupational cohort of police officers, has enabled analyses of persons seroconverting with estimated times of seroconversion among HIV-1 and HIV-2-infected individuals, allowing incidence measurements while the Bissau HIV Cohort and a newer Nationwide HIV Cohort have provided clinical data on large numbers of HIV-infected patients. The HIV cohorts in Guinea-Bissau are unique platforms for research and represent real life in many African countries. Poor adherence, lack of HIV viral load measurements, inadequate laboratory facilities, high rates of loss to follow-up, mortality, treatment failure and resistance development, are just some of the challenges faced putting the goal of "90-90-90″ for Guinea-Bissau well out of reach by 2020. Maintaining undetectable viral loads on treatment as a prerequisite of a cure strategy seems not possible at the moment. Thinking beyond one-pill-once-a-day, long-acting antiretroviral treatment options such as injectable drugs or implants may be a better treatment option in settings like Guinea-Bissau and may even pave the way for an HIV cure. If the delivery of antiretroviral treatment in sub-Saharan Africa in a sustainable way for the future should be improved by focusing on existing treatment options or through focusing on new treatment options remains to be determined.

Long-term effects of smallpox vaccination on expression of the HIV-1 co-receptor CCR5 in women.

BACKGROUND: Smallpox vaccinations were stopped globally in 1980. Recent studies have shown that in women, being smallpox vaccinated was associated with a reduced risk of HIV infection compared with not being smallpox vaccinated. At the initial infection, HIV-1 most often uses CCR5 as a co-receptor to infect the T-lymphocytes. We therefore investigated whether smallpox vaccination is associated with a down-regulation of CCR5 on the surface of peripheral T-lymphocytes in healthy women in Guinea-Bissau. METHODS: We included HIV seronegative women from Bissau, Guinea-Bissau, born before 1974, with and without a smallpox vaccination scar. Blood samples were stabilised in a TransFix buffer solution and stained for flow cytometry according to a T-cell maturation profile. RESULTS: Ninety-seven women were included in the study; 52 with a smallpox vaccination scar and 45 without a scar. No association between smallpox vaccination scar and CCR5 expression was found in any T-lymphocyte subtype. CONCLUSION: Among HIV seronegative women, being smallpox vaccinated more than 40 years ago was not associated with a down-regulation of CCR5 receptors on the surface of peripheral T-lymphocytes.

The challenge of discriminating between HIV-1, HIV-2 and HIV-1/2 dual infections.

OBJECTIVES: Discrimination between HIV-1 and HIV-2 is important to ensure appropriate antiretroviral treatment (ART) and epidemiological surveillance. However, serological tests have shown frequent mistyping when applied in the field. We evaluated two confirmatory tests, INNO-LIA HIV I/II Score and ImmunoComb HIV 1/2 BiSpot, for HIV type discriminatory capacity. METHODS: Samples from 239 ART-naïve HIV-infected patients from the Bissau HIV Cohort in Guinea-Bissau were selected retrospectively based on the initial HIV typing performed in Bissau, ensuring a broad representation of HIV types. INNO-LIA results were interpreted by the newest software algorithm, and three independent observers read the ImmunoComb results. HIV-1/HIV-2 RNA and DNA were measured for confirmation. RESULTS: INNO-LIA results showed 123 HIV-1 positive samples, 69 HIV-2 positive and 47 HIV-1/2 dually reactive. There was agreement between INNO-LIA and HIV-1/HIV-2 RNA and DNA detection, although not all HIV-1/2 dually reactive samples could be confirmed by the nucleic acid results. Overall, the observers found that the ImmunoComb results differed from the INNO-LIA results, with agreements of 90.4, 91.2 and 92.5%, respectively, for HIV-1, HIV-2 and HIV-1/2. The combined kappa-score for agreement between the three observers was 0.955 (z-score 35.1; P < 0.01). Of the HIV-2 mono-reactive samples (INNO-LIA), the three observers interpreted 24.6-31.9% as HIV-1/2 dually infected by ImmunoComb. None of these samples had detectable HIV-1 RNA or DNA. CONCLUSIONS: There was accordance between INNO-LIA calls and nucleic acid results, whereas ImmunoComb overestimated the number of HIV-1/2 dually infected patients. Confirmatory typing is needed for patients diagnosed with HIV-1/2 dual infection by ImmunoComb.

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

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.

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.

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.

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.

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.