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Background: HTLV-1 is endemic in Guinea-Bissau, and the highest prevalence in the adult population (5.2%) was observed in a rural area, Caió, in 1990. HIV-1 and HIV-2 are both prevalent in this area as well. Cross-sectional associations have been reported for HTLV-1 with HIV infection, but the trends in prevalence of HTLV-1 and HIV associations are largely unknown, especially in Sub Saharan Africa. In the current study, data from three cross-sectional community surveys performed in 1990, 1997 and 2007, were used to assess changes in HTLV-1 prevalence, incidence and its associations with HIV-1 and HIV-2 and potential risk factors., Results: HTLV-1 prevalence was 5.2% in 1990, 5.9% in 1997 and 4.6% in 2007. Prevalence was higher among women than men in all 3 surveys and increased with age. The Odds Ratio (OR) of being infected with HTLV-1 was significantly higher for HIV positive subjects in all surveys after adjustment for potential confounding factors. The risk of HTLV-1 infection was higher in subjects with an HTLV-1 positive mother versus an uninfected mother (OR 4.6, CI 2.6-8.0). The HTLV-1 incidence was stable between 1990-1997 (Incidence Rate (IR) 1.8/1,000 pyo) and 1997-2007 (IR 1.6/1,000 pyo) (Incidence Rate Ratio (IRR) 0.9, CI 0.4-1.7). The incidence of HTLV-1 among HIV-positive individuals was higher compared to HIV negative individuals (IRR 2.5, CI 1.0-6.2), while the HIV incidence did not differ by HTLV-1 status (IRR 1.2, CI 0.5-2.7)., Conclusions: To our knowledge, this is the largest community based study that has reported on HTLV-1 prevalence and associations with HIV. HTLV-1 is endemic in this rural community in West Africa with a stable incidence and a high prevalence. The prevalence increases with age and is higher in women than men. HTLV-1 infection is associated with HIV infection, and longitudinal data indicate HIV infection may be a risk factor for acquiring HTLV-1, but not vice versa. Mother to child transmission is likely to contribute to the epidemic.

Objectives: To assess changes in HIV incidence and prevalence in Caió, a rural area of Guinea-Bissau, between 1990 and 2007., Design: Three cross-sectional community surveys., Methods: In 1990, 1997, and 2007, surveys were conducted among adults. The prevalence of HIV-1 and of HIV-2 was estimated for each survey, and incidence rates were calculated for the first (1990-1997) and second period (1997-2007)., Results: The HIV-1 incidence was approximately 4.5/1000 person-years in the two periods, whereas the HIV-2 incidence decreased from 4.7 (95% confidence interval 3.6-6.2) in the first to 2.0 (95% confidence interval 1.4-3.0) per 1000 person-years in the second period (P < 0.001). HIV-1 prevalence rose from 0.5% in 1990 to 3.6% in 2007, and HIV-2 prevalence decreased from 8.3% in 1990 to 4.7% in 2007. HIV-1 prevalence was less than 2% in 15 to 24 year olds in all surveys and was highest (7.2%) in 2007 among 45 to 54 year olds. The HIV-2 prevalence was fivefold higher in older subjects (> or =45 yr) compared with those less than 45 years in both sexes in 2007., Conclusions: HIV-1 incidence is stable, and its prevalence is increasing, whereas HIV-2 incidence and prevalence are both declining. In contrast with what has been observed in other sub-Saharan countries, HIV-1 prevalence is lower in younger age groups than older age groups.

Background: Although AIDS is less frequent following HIV-2 than HIV-1 infection, it is unclear whether the clinical picture and clinical course of AIDS are similar in the two infections., Objectives: To compare the pattern of AIDS-defining events, CD4 cell count at the time of AIDS diagnosis, survival from time of AIDS, and CD4 cell count near time of death in HIV-1 and HIV-2-infected patients., Methods: Adult patients with AIDS who attended the clinics of the MRC in The Gambia were enrolled. AIDS was diagnosed according to the expanded World Health Organization case definition for AIDS surveillance (1994)., Results: Three hundred and forty-one AIDS patients with HIV-1 and 87 with HIV-2 infection were enrolled. The most common AIDS-defining events in both infections were the wasting syndrome and pulmonary tuberculosis. The median CD4 cell count at AIDS was 109 cells/microl in HIV-1 and 176 in HIV-2 (P = 0.01) and remained significantly higher in HIV-2 after adjustment for age and sex (P = 0.03). The median time to death was 6.3 months in HIV-1 and 12.6 months in HIV-2-infected patients (P = 0.03). In a multivariable analysis adjusting for age, sex and CD4 cell count, the mortality rates of HIV-1 and HIV-2-infected patients were similar (P = 0.25). The median CD4 cell count near time of death was 62 and 120 cells/microl in HIV-1 and HIV-2-infected patients, respectively (P = 0.02)., Conclusions: HIV-2 patients have a higher CD4 cell count at the time of AIDS, and a longer survival after AIDS. The mortality after an AIDS diagnosis is more influenced by CD4 cell count than HIV type.

Background: The HIV-1 epidemic in West Africa is characterized by a slower rise than that in Eastern and Southern Africa. The HIV-2 epidemic in West Africa may be declining, but few long-term data exist., Methods: In a research clinic in The Gambia, HIV-1 and HIV-2 prevalence trends among all new patients being tested for HIV were examined over a 16 year period (1988 till 2003). In newly diagnosed patients a baseline CD4 count was done., Results: An HIV test was done in 23 363 patients aged 15 years or older. The prevalence of HIV-1 was 4.2% in 1988-91 and rose to 17.5% in 2001-03 (P < 0.0001, chi(2)-test for trend). The prevalence of HIV-2 was 7.0% in 1988-91 and declined to 4.0% in 2001-03 (P < 0.0001). HIV-1 prevalence increased and HIV-2 prevalence decreased with time in logistic regression models adjusting for age, sex, and indication for test (P < 0.0001). Baseline CD4 counts were available for 65% of patients. The median CD4 count was 215 cells/mm3 [interquartile range (IQR) 72-424] for HIV-1, and 274 (IQR 100-549) for HIV-2 infected patients. There was no marked trend of rise or decline in baseline CD4 count in either HIV-1 or HIV-2 infected patients over the study period. Forty-five per cent of newly diagnosed HIV patients had a CD4 count <200 cells/mm3., Conclusions: These data suggest that HIV-1 prevalence is rising in The Gambia, and that HIV-2 is declining. HIV patients in The Gambia present late and almost half of patients would qualify for anti-retroviral treatment at their first visit.

Simple robust approaches are needed to monitor the prevalence and incidence of HIV in Africa. The aim of this study was to evaluate the use of dried blood spot (DBS) as an alternative to serum or plasma for sentinel surveillance. Paired DBS and blood samples were obtained from 200 patients attending a genito-urinary medicine clinic in West Africa. The gold standard of diagnosis was based on the combination of 3 enzyme-linked immunosorbent assays (ELISA) using serum. The presence of HIV antibodies in eluates of dried blood spots was detected by ELISA, Gelatin Particle Assay (GPA) and Pepti-Lav 1-2 in 5 different testing strategies. All 200 eluates were tested individually, and in addition pools of 5 eluates each were tested. The sensitivity of the testing strategies ranged from 95.0% (83.1 - 99.4%) to 100% and the specificity from 97.5% (93.7 - 99.3%) to 100%. Testing in pools of 5 did not affect sensitivity. Dried blood spots were easy to work with. Test kit and laboratory consumable costs varied between 492 pounds and 1037 pounds (unpooled strategies) and 163 pounds and 421 pounds (pooled). The monospecific ELISAs used in this study are no longer in production; currently available differentiating assays need to be tested. DBS are recommended for sentinel surveillance in Africa.

The mechanisms underlying the relatively slow progression of human immunodeficiency virus type 2 (HIV-2) compared with HIV-1 infection are undefined and could be a result of more effective immune responses. We used HIV-2 and HIV-1 IFN-gamma enzyme-linked immunospot assays to evaluate CD8(+) T cell responses in antiretroviral-naive HIV-2- ('HIV-2(+)') and HIV-1-infected ('HIV-1(+)') individuals. Gag-specific responses were detected in the majority of HIV-2(+) and HIV-1(+) subjects. Overlapping gag peptide analysis indicated a significantly greater magnitude and breadth of responses in the HIV-1(+) cohort, and this difference was attributable to low responses in HIV-2(+) subjects with undetectable viral load (medians 2107 and 512 spot-forming units per 10(6) PBMC, respectively, p=0.007). We investigated the phenotype of viral epitope-specific CD8(+) T cells identified with HLA-B53- and HLA-B58-peptide tetramers (8 HIV-2(+), 11 HIV-1(+) subjects). HIV-2-specific CD8(+) T cells were predominantly CD27(+) CD45RA(-), and only a minority expressed perforin. The limited breadth and low frequency of CD8(+) T cell responses to HIV-2 gag in aviremic HIV-2(+) subjects suggests that these responses reflect antigen load in plasma, as is the case in HIV-1 infection. Immune control of HIV-2 does not appear to be related to the frequency of perforin-expressing virus-specific CD8(+) T cells.

Objectives: To estimate and compare the all-cause mortality rates among HIV-1-infected, HIV-2-infected, and uninfected women and to assess the predictive value of baseline plasma viral load (PVL) and CD4 cell percentage (CD4%) for mortality., Design: Cohort study., Methods: At presentation to antenatal clinics in The Gambia in 1993-1995, pregnant women were screened for antibodies to HIV-1 and HIV-2. Seropositive subjects and a similar number of seronegative controls were enrolled, and baseline PVL and CD4% were measured. Participants were visited regularly by field-workers until 18 months after delivery and again 4-7 years later., Results: Thirty-two of 101 women infected with HIV-1, 23 of 243 infected with HIV-2, and 9 of 468 seronegative women died during a median follow-up of 6.9 years. The mortality rate was 56 deaths per 1000 person years of observation (pyo) for HIV-1-infected, 16 deaths per 1000 pyo for HIV-2-infected, and 3.1 deaths per 1000 pyo for HIV-uninfected women. After 8 years of follow-up, >50% of HIV-1-infected women were still alive. In multivariate analysis, a 1-log increase of HIV-1 PVL was associated with a 1.8-fold higher rate of mortality (95% confidence interval [CI], 0.9-3.4). In HIV-2 infection, women with a high PVL (>10,000 copies/mL) had an 8.7-fold (95% CI, 2.8-28) higher rate of mortality than did those with a low PVL (<1000 copies/mL). A 10% decrease in CD4% was associated with higher mortality rates among HIV-1-infected (1.6-fold; 95% CI, 1.1-2.3) and HIV-2-infected (1.5-fold; 95% CI, 1.0-2.3) subjects., Discussion: Survival of HIV-1-infected women in The Gambia is similar to that in industrialized countries before the introduction of antiretroviral treatment. Survival of HIV-2-infected women is much better. However, women with high PVLs die as quickly as their HIV-1-infected counterparts.

Background: Identification of basic prognostic indicators of HIV infection is essential before widespread antiretroviral therapy can be implemented in low-technology settings. This study assessed how well body mass index (BMI:kg/m2) predicts survival., Methods: BMI within 3 months of HIV diagnosis was obtained from 1657 patients aged > or = 15 years, recruited in a seroprevalent clinical cohort in The Gambia since 1992 and followed up at least once. Baseline CD4+ counts and clinical assessment at time of diagnosis were done., Results: The mortality hazard ratio (HR) of those with a baseline BMI <18 compared with those with a baseline BMI > or = 18 was 3.4 (95% CI, 3.0-3.9). The median survival time of those presenting with a BMI <16 was 0.8 years, in contrast to a median survival of 8.9 years for those with a baseline BMI > or = 22. Baseline BMI <18 remained a highly significant independent predictor of mortality after adjustment for age, sex, co-trimoxazole prophylaxis, tuberculosis, reported wasting at diagnosis, and baseline CD4+ cell count (adjusted HR = 2.5, 95% CI 2.0-3.0). Sensitivity and specificity of baseline BMI <18 was comparable to that of a CD4+ count <200 in predicting mortality within 6 months of diagnosis., Discussion: BMI at diagnosis is a strong, independent predictor of survival in HIV-infected patients in West Africa. In the absence of sophisticated clinical and laboratory support, BMI may also prove a useful guide for deciding when to initiate antiretroviral therapy.

Background: In sub-Saharan Africa, tuberculosis (TB) is the most frequently diagnosed opportunistic infection and cause of death among HIV-infected patients. HIV-2 has been associated with less immune suppression, slower disease progression and longer survival., Objective: To examine whether the incidence of TB and survival after TB are associated with CD4 cell count rather than HIV type., Methods: Clinical and immunological data were retrospectively evaluated among an open clinic-based cohort of HIV-1- and HIV-2-infected patients to determine incidence of TB (first diagnosis > 28 days after HIV diagnosis) and subsequent mortality. Patients were grouped by CD4 cell count into those with < 200, 200-500 and > 500 x 10 cells/l., Results: Incident TB was diagnosed among 159 of 2012 patients, with 4973 person-years of observation time. In 105/159 (66.0%), the diagnosis was confirmed by direct microscopy or culture. Incidence of TB was highest in the group with < 200 x 10 cells/l (9.1/100 and 8.8/100 person-years in HIV-1 and HIV-2, respectively). Adjusted for CD4 cell count, there was no significant difference in incidence or mortality following TB between HIV-1- and HIV-2-infected patients. Mortality rate was higher in those with incident TB and HIV infection, most markedly in the group with the highest CD4 cell count (hazard ratio, 10.0; 95% confidence interval, 5.1-19.7)., Conclusion: Adjusted for CD4 cell count, incidence of TB was similar among HIV-1- and HIV-2-infected patients. Mortality rates after TB diagnosis were similar in both groups and high compared with those without TB.

Fewer people infected with human immunodeficiency virus (HIV) type 2 progress to acquired immunodeficiency syndrome, compared with those infected with HIV-1. To understand the immune mechanisms leading to slow progression in HIV-2 infection, cell-mediated immune responses were compared between the 2 infections in asymptomatic subjects with a CD4 cell count > or =20%. Interferon- gamma release from T lymphocytes and the cytotoxicity of CD8+ T lymphocytes were measured by ELISPOT and 51Cr release assays. The level of responses and the proportion of responders were similar in the 2 infections, despite a 20-fold difference in their geometric mean plasma virus loads. The proliferation of CD4+ T helper cells, which was evaluated by thymidine incorporation, was not different between the 2 infections. Contrary to widely held views, our results suggest that nonprogression in HIV-2 infection may not be due to more vigorous immune responses.

Background: The risk of mother-to-child transmission (MTCT) of HIV-2 is much lower than that of HIV-1, but the long-term prognosis of perinatally infected HIV-2 children is unknown. We re-visited children who were part of a large MTCT study in The Gambia (conducted during 1993-1997), in order to compare the long-term survival of children perinatally infected with HIV-2 with that of seronegative and of HIV-1 infected children., Methods: Five to eight years' follow-up of a cohort of children born to HIV-negative, HIV-1 positive, and HIV-2 positive mothers., Results: Seven hundred and seventy-four children were followed up for a median of 6.6 years. Of 17 perinatally HIV-1 infected children, three were still alive on 1 July 2001, two had been lost to follow-up, and 12 had died. The median survival was 2.5 years. Of eight HIV-2 infected children five were still alive, none were lost to follow-up and three had died. The mortality hazards ratio of both HIV-1 [9.9; 95% confidence interval (CI), 5.2-19], and of HIV-2 infected children (3.9; CI, 1.2-12) was significantly increased compared with children of seronegative mothers. The mortality hazards ratio of HIV uninfected children of HIV-1 or HIV-2 infected mothers was not significantly increased compared to that of children of seronegative mothers (P = 0.17 and P = 0.5 respectively)., Conclusions: Children with perinatally acquired HIV-2 infection have a higher mortality than children of seronegative mothers. Guidelines for treatment of HIV-1 infected children should be used for treatment of HIV-2 infected children.

Objective: To monitor HIV-1 and HIV-2 trends in The Gambia, West Africa., Methods: In 1993-1995 a nationwide survey among 29 670 pregnant women attending eight antenatal clinics estimated the seroprevalence of HIV-1 at 0.6%, and of HIV-2 at 1.1%. Five years later, sentinel surveillance in pregnant women was established, using unlinked anonymous testing in four clinics. A dried blood spot on filter paper was obtained and tested for HIV antibodies., Results: Between May 2000 and August 2001, 8054 analysable samples were collected at four sites. The prevalence of HIV-1 rose sharply in one rural area from 0.6 to 3.0% (P < 0.0001), but the increase was small and non-significant in two other rural sites and in the urban site. The prevalence of HIV-2 did not change significantly at any of the sites. The overall prevalence of HIV-1 was 1.0% [95% confidence interval (CI) 0.8-1.3%], and of HIV-2 0.8% (CI 0.6-1.0%). Site, nationality and higher age were significantly associated with HIV-1 infection, and higher parity and site were significantly associated with HIV-2 infection., Conclusion: Fifteen years after the first case of HIV-1 was described in The Gambia, the epidemic is still at a low level. There is heterogeneity within the country, with one rural area experiencing a fivefold increase in 6 years. The prevalence of HIV-2 in The Gambia is stable.

Objective: To examine baseline plasma viral loads according to the CD4 cell percentage (CD4%) in HIV-1, HIV-2 and dually infected patients (HIV-D), and to relate these measurements to survival., Patients and Methods: A total of 119 HIV-1, 137 HIV-2 and 81 HIV-D-infected patients attending the Medical Research Council clinic in The Gambia were recruited from 1991 according to baseline CD4%, and followed until death or the end of December 2000. HIV-1 and HIV-2 RNA levels were measured by in-house reverse transcriptase polymerase chain reaction assays., Results: The plasma viral load, which varied inversely with CD4%, was similar in HIV-1 singly and dually infected patients, but was significantly higher in HIV-1 than in HIV-2 singly infected patients, except in those with a CD4% less than 14%. HIV-2 plasma viral load in dually infected patients did not vary significantly with CD4%, but was significantly lower than in HIV-2 singly infected patients with CD4% less than 14%. Multivariate analysis showed that only CD4% was independently associated with survival in HIV-1 and HIV-D infections; whereas both CD4% and plasma viral load were independently associated with survival in HIV-2 infections. The mortality rate of HIV-D-infected patients was not significantly different from that of HIV-1-infected patients, but was significantly higher in the absence of HLA B58., Conclusion: HIV-2 infection does not alter HIV-1 replication or prolong survival in dually infected patients. In a clinical setting in Africa, where many patients present with advanced disease, CD4% may be a more important predictor of prognosis than plasma viral load.

Objectives: To determine the rates of, and risk factors for, mother-to-child transmission (MCT) of HIV-1 and HIV-2 infection in The Gambia., Design: A blinded, prospective, community-based cohort study of 29.549 pregnant women attending the eight largest antenatal clinics in The Gambia., Methods: Women were tested for HIV-1 and HIV-2 infection. Infected subjects and a group of HIV-seronegative women were followed with their babies until 18 months after delivery. Maternal CD4 cell count percentages were measured before and 18 months after delivery, and the antenatal plasma viral load was determined. Babies were tested for HIV by the polymerase chain reaction and/or serology at 2, 9 and 18 months of age., Results: The study enrolled 144 women positive for HIV-1 and 294 for HIV-2 plus 565 seronegative pregnant women: the mean antenatal percentage CD4 cell counts of 96 HIV-1-positive, 223 HIV-2-positive and 125 HIV-seronegative mothers were 31% [95% confidence interval (CI) 28-33], 41% (95% CI 39-42) and 47% (95% CI 45-49), respectively. The geometric mean antenatal plasma viral load of 94 HIV-1-infected women was 15,100 copies x 10(3) ml (95% CI 10,400-19,000) which was much higher than that of 60 randomly selected HIV-2-infected women, which was 410 copies x 10(3) ml (95% CI 150-910) (P < 0.001). The estimated transmission rate of HIV-1 was 24.4% (95% CI 14.6-33.9) and that of HIV-2 was 4.0% (95% CI 1.9-7.4). Five of 17 HIV-1-positive and three of eight HIV-2-positive babies were infected after 2 months of age. Birth in the rainy season [odds ratio (OR) 2.9; 95% CI 1.2-7.2], a low postnatal CD4 cell percentage (OR for a 10% fall 2.4; 95% CI 1.1-5.1) and a high maternal plasma viral load (OR for a 10-fold increase 2.9; 95% CI 1.1-7.8) were risk factors for transmission that applied equally to both viruses., Conclusion: Low maternal HIV-2 RNA levels, which on average are 37-fold less than in HIV-1 infection, relate to the low MCT rate of HIV-2.