Anders Nauclér

9-year HIV-2-associated mortality in an urban community in Bissau, west Africa

BACKGROUND Community studies with 1-3 years of follow-up have reported four to five times higher mortality in HIV-2-infected than in uninfected adults. In a cohort study of HIV-1, an increasing difference in mortality rates of HIV-1-infected and uninfected individuals is expected over time, because of rising mortality with advancing HIV-1 infection. We therefore investigated long-term survival of HIV-2-infected adults. METHODS Adults enrolled in 1987 in a community study of HIV-2 infection in Guinea-Bissau were followed up with serological surveys in 1989 and 1992. Survival was assessed in 1995, 9 years after enrollment. FINDINGS The annual incidence of HIV-2 was 0.7% for adults and tended to be higher for older individuals than for participants aged 15-44 years (relative risk 3.21 [95% CI 0.91-11.37]). With control for age, HIV-2-infected adults had twice as high mortality as uninfected individuals (mortality ratio 2.32 [1.18-4.57]); the mortality ratio was highest in the first year of the study (4.50 [1.31-15.43]). The difference between infected and uninfected individuals was stronger for adults under 45 years of age (mortality ratio 4.72 [1.86-11.97]) than for older people (1.35 [0.51-3.56]). HIV-2-infected individuals living with an infected spouse had significantly higher mortality than HIV-2-infected individuals living with an uninfected spouse (p = 0.027). INTERPRETATION HIV-2-associated mortality is not increasing with length of follow-up. Mortality in HIV-2-infected adults is only twice as high as that in uninfected individuals. In the majority of adults, HIV-2 has no effect on survival.

A prospective study of vertical transmission of HIV-2 in Bissau, Guinea-Bissau.

OBJECTIVES To determine the vertical transmission rate of HIV-2 and clinical findings associated with vertically transmitted HIV-2 infection. DESIGN A prospective study of HIV-2 transmission in children of HIV-2-seropositive mothers, and a comparison of clinical findings between children of seropositive and seronegative mothers. SETTING Recruitment of women delivering at the national hospital in Bissau, Guinea-Bissau. Follow-up by home visits. SUBJECTS AND METHODS Eighty-six newborns of 82 HIV-2-seropositive mothers and a control group of 102 newborns of HIV-seronegative mothers were followed-up clinically and by HIV serology until the children reached the age of 20 months. RESULTS Of the 86 children of seropositive mothers, 51 had a complete follow-up, 22 died and 13 were lost due to change of residence. Of the 102 children of seronegative mothers, 63 had a complete follow-up, 13 died and 26 were lost due to change of residence. None of 51 children of seropositive mothers had serological evidence of HIV-2 infection at the end of the follow-up period. There was no significant difference in the frequency of clinical symptoms between the children in the study group and the children in the control group. The mortality during the first year of life was not significantly different between the children of seropositive and seronegative mothers (13 out of 80 and 11 out of 94, respectively, P > 0.05, excluding children lost to follow-up). Only three of the dead children of seropositive mothers and one of the dead children of seronegative mothers had any symptoms that might be related to HIV-2 infection (diarrhoea > 1 month). CONCLUSION Vertical transmission of HIV-2 appears to be rare.

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.

Declining Hiv-2 prevalence and incidence among men in a community study from Guinea-bissau

Objective:To assess the present level of HIV-2 infection in an adult population in Bissau and to evaluate sex and age-specific changes in HIV-2 prevalence and incidence between 1987 and 1996. Design and methods:Sex and age-specific changes in HIV-2 prevalence were evaluated comparing a survey from 1987 in a sample of 100 houses with a survey performed in 1996 in an independent sample of 212 houses from the same study area. HIV-2 incidence rates were examined in an adult population (age ≥ 15 years) from 100 randomly selected houses followed with four consecutive HIV serosurveys from 1987 to 1996. Results:The HIV-2 prevalence in 1996 was 6.8% (men, 4.7%; women, 8.4%). Compared with the 1987 survey there was a significant decrease in prevalence among men [age-adjusted relative risk (RR), 0.50; 95% confidence interval (CI), 0.31–0.83], whereas it remained unchanged in women (RR, 1.00; 95% CI, 0.67–1.48). The male-to-female RR decreased from 0.99 (95% CI, 0.61–1.61) in 1987 to 0.51 (95% CI, 0.34–0.76) in 1996. The overall annual incidence rate was 0.54 per 100 person-years of observation (PYO), being higher in women (0.72 per 100 PYO) than in men (0.31 per 100 PYO). With the observation time divided into an early and a late period, there was a decrease in incidence with time among men (0.66 to 0.00 per 100 PYO), but no major change among women (0.59 to 0.85 per 100 PYO). The two trends differed significantly (P = 0.03). We observed a higher annual incidence rate amongst older women aged > 44 years (1.77 per 100 PYO) than among younger women (0.55 per 100 PYO; P = 0.05). Conclusion:There are no signs of an epidemic spread of HIV-2 in Bissau even though the HIV-1 prevalence is increasing rapidly. A significant reduction in the male HIV-2 prevalence and incidence rates has resulted in a major shift in the pattern of spread of HIV-2, from being equally distributed to being predominantly a female infection. Currently, older women in particular seem to have a high risk of getting infected.

Prevalences of HTLV-1 infection and associated risk determinants in an urban population in Guinea-Bissau, West Africa.

Objective: To assess the prevalence and modes of transmission of HTLV‐1 infection in an adult population in Bissau, and to evaluate possible interactions between the pattern of spread of HTLV‐1 and HIV‐1/HIV‐2. Design and Methods: Univariate and multivariate analyses were used to evaluate gender‐ and age‐specific HTLV‐1 prevalences as well as associated risk determinants in an adult population based on a serosurvey comprising 2127 individuals from 304 randomly selected houses in Bissau. Results: Using stringent Western blot criteria, the overall seroprevalence of HTLV‐1 was 3.6%, 2.2% among men and 4.7% among women, respectively. One individual was seropositive to HTLV‐2. The prevalence of HTLV‐1, which increased with age in both genders, however more markedly among women, was >4 times higher (9.4%) among older individuals (>44 years of age) than among younger individuals (2.4%). Blood transfusion and HIV‐2 seropositivity were independently associated with HTLV‐1 seropositivity in men. Among women, both HIV‐2 seropositivity and HIV‐1 seropositivity were significant risk determinants. Having had sexual partners was associated with a fivefold increased risk among women but did not reach significance. Conclusion: The adult population of Guinea‐Bissau has a higher prevalence of HTLV‐1 than reported from most other countries in West Africa. The gender‐ and age‐specific pattern of spread of HTLV‐1 closely resembles that observed for HIV‐2, another retrovirus prevalent to the region. The close correlation between HTLV‐1 and HIV‐2 most likely reflects the shared risk factors related to sexual behavior. The implication of the high percentage of double infections in this population needs to be determined.

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.

Clinical Predictors for Death in HIV-positive and HIV-negative Tuberculosis Patients in Guinea-Bissau.

Object:To assess easily monitored predictors for tuberculosis mortality.Design:Risk factors for tuberculosis mortality were assessed during the 8-month treatment in 440 men and 269 women diagnosed with confirmed or presumed intrathoracic tuberculosis included prospectively in Guinea-Bissau from May 1996 to April 2001. A civil war occurred in the study area from June 1998 to May 1999.Results:12% were HIV-1 positive, 16% HIV-2 positive and 7% were HIV dually infected. Case fatality rates for HIV positive were higher during (35% [22/63]) and after the war (29% [27/92]) compared to before the war (17% [15/88]). The war did not have an effect on the case fatality rate in HIV negative (10% [13/135] before the war). HIV-1-infected patients had higher mortality than HIV-2 infected, mortality rate ratio (MRR) = 2.28 (95% confidence interval 1.17–4.46). Men had higher mortality than women but only among the HIV negative (MRR = 2.09 [0.95–4.59]). Hence, the negative impact of HIV infection on mortality was stronger in women (MRR = 6.51 [2.98–4.2]) than in men (MRR = 2.64 [1.67–4.17]) (test of homogeneity, p = 0.051). Anergy to tuberculin was associated with death in HIV positive (MRR = 2.77 [1.38–5.54]) but not in HIV negative (MRR = 1.14 [0.52–2.53]). Signs of immune deficiency, such as oral candida infection or leukoplakia (MRR = 4.25 [1.92–9.44]) and diarrhea (MRR = 2.15 [1.29–3.58] was associated with mortality in HIV positive. Tendencies were similar among HIV negative. HIV-positive relapse cases were at increased risk of dying (MRR = 2.42 [1.10–5.34]). Malnutrition, measured through mid-upper arm circumference (MUAC), increased the risk of death.Conclusion:Easily monitored predictors for mortality in tuberculosis patients include clinical signs of immune deficiency and low MUAC.

Replicative capacity of HIV-2, like HIV-1, correlates with severity of immunodeficiency.

We have obtained 15 HIV-2 isolates from the peripheral blood mononuclear cells (PBMCs) of 24 HIV-2-infected west African people. The frequency of virus isolation correlated with the severity of HIV-2 infection; only three isolates were obtained from 11 asymptomatic individuals, whereas virus was isolated from nearly all (12 of 13) individuals with symptoms. The HIV-2 isolates showed distinct replicative and cytopathic characteristics and, similarly to HIV-1 isolates, could be divided into two major groups: rapid/high and slow/low. Rapid/high isolates, i.e. isolates with the ability to replicate in tumour cell lines, were obtained from individuals with symptomatic HIV-2 infection and CD4+ lymphocyte counts less than 360/microliters blood; these isolates induced syncytia in PBMC cultures. HIV-2 isolates unable to replicate continuously in tumour cell lines (slow/low isolates) induced small syncytia, cell death, or no cytopathic effect at all. All HIV-2 isolates obtained from asymptomatic individuals showed a slow/low replication pattern.

HIV-1, HIV-2, HTLV-I/II and Treponema pallidum infections: incidence, prevalence, and HIV-2-associated mortality in an occupational cohort in Guinea-Bissau.

The prevalence and incidence of human immunodeficiency virus types 1 and 2 (HIV-1, HIV-2), human T-lymphotropic virus types I and II (HTLV-I/II), and syphilitic infections and the association between these infections were determined in a cohort of police officers in Guinea-Bissau. Between January 1990 and December 1992, 1,384 subjects (1,241 men and 143 women) were included in the study; and of the first 879 tested, 561 were tested at least for a second time. The overall seroprevalence of HIV-1 was 0.4%, of HIV-2 11.6%, and of HTLV I/II 4.4%. Three individuals (0.2%) were seropositive for both HIV-1 and HIV-2. Women had a significantly higher prevalence of HIV-2 infection than men (16.8% and 11.0%, respectively, p < 0.05). Serologic evidence of previous syphilis was present in 12.1% and was significantly more common in men (12.7%) than in women (7.0%) (p < 0.05). There was a significant association between the prevalence of HIV-2 and HTLV-I/II infection (p < 0.05). The annual incidence of HIV-1 was 0.7%, of HIV-2 1.6%, of HTLV I/II 0.4%, and of syphilis 1.7%. There was no association between the incidence of the various infections. The death rate (per 100 person-years) was significantly higher among HIV-2-infected individuals (2.7%) than among HIV-negative individuals (0.5%) (relative risk = 5.1; 95% confidence interval, 2.1-12.2; p < 0.001). HIV-related symptoms were more frequent among the HIV-2-positive individuals who died compared with the seronegative individuals who died (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

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.