Virological and immunological response to Combivir and emergence of drug resistance mutations in a cohort of HIV-2 patients in The Gambia.
Explore the source record for details and available documents.
Anti-HIV Agents↗
Biomedical subjects
Ramu Sarge-Njie
Publications and source records attributed to Ramu Sarge-Njie.
Sixteen years of HIV surveillance in a West African research clinic reveals divergent epidemic trends of HIV-1 and HIV-2.
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.
Adolescent↗
Evaluation of the dried blood spot filter paper technology and five testing strategies of HIV-1 and HIV-2 infections in West Africa.
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.
AIDS Serodiagnosis↗
Baseline plasma viral load and CD4 cell percentage predict survival in HIV-1- and HIV-2-infected women in a community-based cohort in The Gambia.
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.
Adolescent↗
CD8+ T cell responses to human immunodeficiency viruses type 2 (HIV-2) and type 1 (HIV-1) gag proteins are distinguishable by magnitude and breadth but not cellular phenotype.
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.
Amino Acid Sequence↗
Body mass index at time of HIV diagnosis: a strong and independent predictor of survival.
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.
Adolescent↗
Incidence of tuberculosis and survival after its diagnosis in patients infected with HIV-1 and HIV-2.
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.
AIDS-Related Opportunistic Infections↗
No differences in cellular immune responses between asymptomatic HIV type 1- and type 2-infected Gambian patients.
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.
Adult↗
Survival of HIV-1 and HIV-2 perinatally infected children in The Gambia.
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.
Developing Countries↗
Regional differences in HIV trends in The Gambia: results from sentinel surveillance among pregnant women.
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.
Age Factors↗
Plasma viral load, CD4 cell percentage, HLA and survival of HIV-1, HIV-2, and dually infected Gambian patients.
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.
Adolescent↗