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Biomedical subjects

H Whittle

Publications and source records attributed to H Whittle.

At least 55 records · Page 3Linked to original sources

Proviral load and immune function in blood and lymph node during HIV-1 and HIV-2 infection.

Proviral load as well as lymphocyte phenotype and function were compared in peripheral blood and lymph node compartments of 17 HIV-1, 12 HIV-2 and three dually infected patients with lymphadenopathy. The mean percentage (95% confidence interval (CI)) of CD4+ cells was higher in lymph node mononuclear cells (LNMC) than in peripheral blood mononuclear cells (PBMC) in both infections, being 26.7% (21. 1%, 32.3%) and 15.3% (10.4%, 20.2%), respectively, for HIV-1-infected patients (P = 0.0001) and 32.3% (22.7%, 41.9%) and 22. 1% (13.6%, 30.6%), respectively, for HIV-2-infected patients (P = 0. 02). In both types of infection, proviral load adjusted for number of CD4+ cells was higher in LNMC than in PBMC: the geometric mean (95% CI) was 8937 (4991; 16 003) and 4384 (2260; 8503), respectively, for HIV-1 patients (P = 0.02) and 1624 (382; 6898) and 551 (147; 2058) DNA copies, respectively, for HIV-2 patients (P = 0.05). Proviral load in both compartments was closely correlated (HIV-1, r = 0.60, P = 0.01; and HIV-2, r = 0.83, P = 0.0003). In both infections, proliferation and interferon-gamma (IFN-gamma) production in response to purified protein derivative (PPD) was lower in LNMC than in PBMC, both of which, in turn, were lower than in healthy controls. These results indicate that in HIV-2 as in HIV-1 infection, infected cells have a tropism for the lymph nodes resulting in higher viral load in this compartment and lower lymphocyte responses to the recall antigen PPD which may increase susceptibility to tuberculosis.

Adult↗

Retinal manifestations of HIV-1 and HIV-2 infections among hospital patients in The Gambia, west Africa.

BACKGROUND: In developed countries, 50-75% of AIDS patients develop retinal complications and about 20-40% acquire cytomegalavirus (CMV) retinitis. We conducted a cross-sectional survey to determine prevalence of these in The Gambia where both HIV-1 and HIV-2 infection are present and the prevalence of HIV-1 is rising. METHOD: All patients attending hospital whose percentage CD4+ cells (CD4%) was below 14, the level associated typically with an AIDS diagnosis, and one half of those whose CD4% was 14 or above were asked to join the study. Fifty-six HIV-1, 52 HIV-2 and 12 dually infected patients were recruited. Photographs of the fundi were taken and interpreted independently. The findings were related to the patients' percentage CD4+ cells. RESULTS: The CD4% was < 14 in 40 patients and < 7 in 17 patients. Thirty-six patients were male. No cases of CMV retinitis were found. Four patients whose CD4% were 4, 5, 11 and 23 had cotton wool spots ranging in number from 1 to 14 for any one patient. The prevalence of cotton wool spots was 8% (95% CI, 0-16%) among patients with CD4% below 14 and 12% (95% CI, 0-27) among patients with CD4% below 7. One of the 4 patients had associated microaneurysm and blot haemorrhages typical of more advanced HIV microvasculopathy. CONCLUSION: CMV retinitis is less common in The Gambia than in developed countries. Non-infectious retinopathy may also be less common.

AIDS-Related Opportunistic Infections↗

Seroconversions in unvaccinated infants: further evidence for subclinical measles from vaccine trials in Niakhar, Senegal.

BACKGROUND: Increases in measles antibodies without rash-illnesses have been documented in previously vaccinated children exposed to measles cases. The phenomenon has been incompletely evaluated in young unvaccinated infants with immunity of maternal origin. METHODS: Monthly cohorts of newborns were prospectively randomized to vaccine and placebo control groups during a trial of high-titre vaccines in Niakhar, Senegal. Measles antibodies were assayed in blood samples of enrolled children collected at 5 months old, when controls received a placebo injection, and at 10 months, when the placebo group was given measles vaccine. Intensive prospective surveillance for measles was conducted throughout the trial. RESULTS: One-fifth (n = 53) of the placebo controls seroconverted, with known exposure to a measles case in only three of them. None of the seroconverters developed a measles-like rash. Sixteen-fold or greater increases in titres were noted in about one-quarter of them. Compared with placebo controls who did not seroconvert, seroconverters were more likely to have had exposure to a measles case and to travel, more likely to be boys than girls, and had significantly lower baseline antibody titres. Measles was endemic in the study area throughout the trial. Seroconversions did not adversely effect subsequent nutritional indices or mortality. CONCLUSIONS: Although laboratory errors and inadvertent injection of vaccine rather than placebo may have played some role, they do not fully explain the above observations, which are consistent with subclinical measles in the seroconverters. The possible role of subclinical measles in occult transmission, its potential effect on the type and duration of subsequent immunity, and its impact on response to primary vaccination need to be determined.

Analysis of Variance↗

Risk factors for severe respiratory syncytial virus infection leading to hospital admission in children in the Western Region of The Gambia.

BACKGROUND: Acute lower respiratory tract infections (ALRI) are the major cause of mortality and morbidity in young children worldwide. Respiratory syncytial virus (RSV) infection is the most important viral cause of severe ALRI but only a small proportion of children infected with this virus develop severe disease. To identify possible risk factors for severe RSV infection leading to hospital admission we have carried out a case-control study of Gambian children with RSV infection admitted to hospital. METHODS: In all, 277 children admitted to three hospitals in the Western Region of The Gambia with lower respiratory tract infection due to RSV were compared with 364 control children matched for age and location of residence who had not been admitted to hospital with an ALRI during the RSV season. A detailed questionnaire covering a wide range of potential social, environmental and nutritional risk factors was administered to the child's guardian. RESULTS: Cases came from larger or more crowded compounds than controls; increased risk was particularly associated with greater numbers of children in the age group 3-5 years living in the compound (odds ratio [OR] for > or =2 children in the age group 3-5 years = 9.1, 95% CI: 3.7-28). Cases were more likely to have a sibling who had died (OR = 3.4, 95% CI: 1.7-7). Controls were more likely to have been exposed to smoke from cooking fires (OR for the mother of cases cooking at least once daily = 0.31, 95% CI: 0.14-0.7). Other protective factors were father's nationality and some professions. Vegetables were included in the diet of controls more frequently than in that of cases (OR = 0.16, 95% CI: 0.06-0.46). Mothers of cases complained of asthma more frequently than mothers of controls, but the number of asthmatic mothers was small (4.2 versus 0.5%, P = 0.05). CONCLUSIONS: Risk factors for severe RSV infection identified in this study are not amenable to public health interventions. Prevention of severe infection is likely to require the development of an effective vaccine.

Case-Control Studies↗

Early two-dose measles vaccination schedule in Guinea-Bissau: good protection and coverage in infancy.

BACKGROUND: Previous studies from Africa have suggested that there is little benefit to be gained from early two-dose measles vaccination schedules. Two-dose schedules have been associated with no improvement in coverage due to immunization of the same individuals on both occasions, low return rate, high refusal rate, low vaccine efficacy, and fear of blunting of the antibody response. Because of the poor results achieved previously with two-dose measles vaccination schedules, we studied patterns of participation, reasons for non-participation, vaccination coverage and relative efficacy of a one-dose versus a two-dose schedule in connection with the implementation of an early two-dose trial in Guinea-Bissau. METHODS: Children born from September 1994 to January 1996 were randomized into two groups receiving either two doses of measles vaccine at 6 and 9 months or one dose of inactivated polio vaccine (IPV) at 6 months and measles vaccine at 9 months. RESULTS: At 6 months of age 86% (1869/2181) of the children participated, and at 9 months of age participation was 87% (1775/2035). The return rate for obtaining a second dose of vaccine was 93% (1647/1773). The main reason for not participating was travelling (78%). Around 50% of those who did not take part in one vaccination took part in the other. When only children participating the first time they were called for a measles vaccination were included, the measles vaccination coverage in the one-dose group was 59% versus 80% in the two-dose group, i.e. a 50% reduction in the risk of not being vaccinated (relative risk [RR] 0.50; confidence interval [CI]: 0.43-0.57). Few measles cases have occurred in the study area since the implementation of the trial making precise estimation of the relative efficacy of the two vaccine strategies difficult, but all seven clinically diagnosed measles cases occurred in the one-dose group making the relative efficacy for the two-dose group compared with the one-dose group 100% (95% CI: 35%-100%; two-tailed P = 0.016). When including maternal reports, the relative efficacy was 90% (95% exact confidence interval; two-tailed P = 25%-97%, P = 0.022). CONCLUSION: In this study of a two-dose measles immunization schedule at 6 and 9 months of age there was no sign of low participation or poor return rates. The risk of not being vaccinated was lower in the two-dose group than in the one-dose group, and the relative efficacy of a two-dose versus a one-dose schedule was high. Although our results were obtained within a trial where dedicated personnel informed every participant personally about the study, we believe our results indicate that with thorough information about the population it may be possible to achieve a higher coverage with a two-dose measles vaccination schedule than a one-dose schedule. A two-dose schedule may be a feasible way to resolve the problems of low coverage and severe measles infection among infants.

Confidence Intervals↗

Increased long term mortality associated with rash after early measles vaccination in rural Senegal.

OBJECTIVES: To examine whether clinical symptoms, including rash, were more common after measles immunization compared with placebo and to study the association between postvaccination symptoms and later mortality. DESIGN: Examination of side effects in the 3 weeks after immunization in a trial of high titer and standard titer measles vaccines. PATIENTS: Two hundred twenty-four children randomly selected to be included in the surveillance for diarrhea, fever and rash. RESULTS: There was no difference in fever and diarrhea between recipients of high titer vaccines and recipients of placebo. However, high titer recipients tended to have more measles-like rashes than placebo recipients [relative risk, 2.12 (range, 0.90 to 5.03)]. Among recipients of high titer vaccines, children who presented a rash had higher mortality in the following 5 to 7 years than those who did not develop rash [mortality rate ratio, 3.85 (range, 1.52 to 9.79)]. High titer recipients without a rash had the same mortality as children in the placebo group who were given standard doses of measles vaccine at 10 months of age [mortality rate, 0.76 (range, 0.35 to 1.62)]. CONCLUSIONS: These observations suggest that in this particular study, rash after high titer measles vaccine may identify children who received a particularly high dose of vaccine or children with more severe and persistent postvaccination immunosuppression. Whether high titer vaccine is more likely than standard titer measles vaccine to provoke such reaction is not known, given that we did not compare side effects after different titers of measles vaccine. Future trials of live measles vaccine should monitor the development of rash.

Cause of Death↗

Poor serologic responses five to seven years after immunization with high and standard titer measles vaccines.

BACKGROUND: Few data exist on the persistence of measles antibodies after vaccination of West African infants. Therefore we examined measles antibody titers 5 to 7 years after children in rural Senegal had received high titer Edmonston-Zagreb (EZ-HT), high titer Schwarz (SW-HT) or standard titer Schwarz (SW-STD) measles vaccines in infancy. METHODS: Children had received either high titer vaccines at 5 months of age or standard titer at 10 months of age. Finger prick blood samples were tested for measles antibody 5 to 7 years later by the hemagglutinin inhibition test. RESULTS: Persistence of antibody after high titer vaccines was poor with the result that 39 and 50% of the EZ-HT and the SW-HT groups had low titers of hemagglutinin inhibition measles antibodies (< or =125 mIU/ml). Nineteen percent of the children in the SW-STD group had low titers which is a lower prevalence than in the high titer groups [relative risk (95% confidence intervals), 0.05 (0.28 to 0.88) vs. EZ-HT; relative risk, 0.38 (0.22 to 0.66) vs. SW-HT]. Geometric mean (95% confidence interval) antibody titers in children with detectable values were 616 (435 to 871) in the EZ-HT, 1106 (616 to 1866) in the SW-HT and 1271 (871 to 1741) mIU/ml in the SW-STD groups, respectively. Multivariant regression analysis showed that mean titers were 2.00 (1.03 to 3.89) times higher for children with low prevaccination antibody titers (< or =125 mIU/ml) and 3.06 (1.90 to 4.94) times higher if blood was collected in the rainy season. INTERPRETATION: Given the rapid decline in antibody titers over a 5- to 6-year period in an area where measles vaccine coverage was high, it seems likely that multiple dose immunization schedules will be needed in the future to maintain protective antibody concentrations (>125 mIU/ml) in West Africa. The role of subclinical boosting by exposure to natural measles and the possible role of malaria, which increases immunoglobulin turnover, in influencing long term antibody persistence after vaccination deserve further investigation.

Antibodies, Viral↗

Etiology of serious infections in young Gambian infants.

BACKGROUND: Despite improvements in infant mortality rates in many developing countries including The Gambia, neonatal mortality remains high and many neonatal deaths are caused by infection. The study described in this paper was conducted to determine the bacterial and viral etiology of serious infections in Gambian infants younger than 91 days old. METHODS: At a first level health facility 497 infants with symptoms that could indicate serious infection were enrolled, of whom 239 with 1 or more signs of serious infection and 55 with no signs were investigated, yielding 17 cases with positive bacterial cultures of blood and/or cerebrospinal fluid. At a nearby pediatric referral hospital 198 infants were seen and 182 were investigated, yielding 35 positive bacterial cultures. RESULTS: There were 15 culture positive cases of meningitis caused by Streptococcus pneumoniae (7), Streptococcus pyogenes (2), Enterobacter cloacae (2), Escherichia coli (1), Haemophilus influenzae type b (1), Streptococcus agalactiae (1) and Salmonella spp. (1). Six of these children died. Thirty-three infants without meningitis had positive blood cultures for Staphylococcus aureus (17), S. pneumoniae (3), Salmonella spp. (5), E. coli (3), other enterobacteria (4) and S. agalactiae (1), of whom 14 died. Nasopharyngeal aspirates from 438 children were investigated for common respiratory viruses. Respiratory syncytial virus was found in 51, influenza A in 46, influenza B in 22, parainfluenza in 26 and adenovirus in 16. Respiratory syncytial virus and influenza A isolates were found most frequently toward the end of the wet season. Nasopharyngeal carriage of S. pneumoniae and H. influenzae was studied in 320 infants recruited during the first year. Of these 184 (58%) were positive for S. pneumoniae and 141 (44%) were positive for H. influenzae, 18 of which were type b. Infants with a bacterial isolate from blood or cerebrospinal fluid were more likely than the rest to die, whereas those with a viral isolate were less likely to die. CONCLUSIONS: The most important causes of serious infections in young Gambian infants are Staphylococcus aureus, S. pneumoniae and Salmonella spp.

Bacteria↗

A randomised trial of a Haemophilus influenzae type b conjugate vaccine in a developing country for the prevention of pneumonia--ethical considerations.

In 1993 a placebo-controlled field trial of a Haemophilus influenzae type b (Hib) conjugate vaccine was started in The Gambia. At that time Hib conjugate vaccines had been shown to be efficacious in Europe and North America for the prevention of Hib meningitis. However doubts remained about their value in developing countries, where the epidemiology of Hib disease is quite different and the most important manifestation of Hib disease is pneumonia. The ethical issues facing the investigators before and during the trial are outlined in this paper, along with the views of the different groups involved in the trial. The trial demonstrated the efficacy of the vaccine in this setting and revealed the proportion of childhood pneumonia that is likely due to Hib, which was much higher than had previously been estimated. Since the completion of the trial Hib vaccines are now recommended for use in developing countries by the World Health Organization, largely based on the results of this trial. After a delay of 17 months following the completion of the trial, national Hib vaccination was started in The Gambia in 1997 using vaccine provided by a donation from industry.

Ethics, Medical↗

Improved detection of HIV-2 proviral DNA in dually seroreactive individuals by PCR.

OBJECTIVE: To improve the detection rate of HIV-2 proviral DNA in primary uncultured peripheral blood mononuclear cells (PBMC) of HIV-2-seroreactive and HIV-1-HIV-2 dually seroreactive individuals. MATERIALS AND METHODS: Two newly designed HIV-2 PCR primer pairs in the long terminal repeat (LTR) gag and gag-pol regions and a previously described env and LTR HIV-2 PCR primer pairs were tested on samples from 66 confirmed HIV-2-seropositive individuals (The Gambia, 40; Côte d'Ivoire, 17; Guinea-Bissau, nine), 209 dually seroreactive individuals (The Gambia, 82; Côte d'Ivoire, 127), 24 genetically characterized isolated HIV-1 strains (group M subtypes A-H and group O), one simian immunodeficiency virus (SIV) strain cpz, 10 HIV-2 isolates (subtype A, B and unidentified), two SIVsm isolates, and 10 seronegative samples. RESULTS: All HIV-2 primers evaluated showed 100% specificity since there was no amplification observed with 24 HIV-1, one SIVcpz and 10 seronegative samples. One single copy of the HIV-2 genome could be detected with all outer primer pairs as well as all inner primer pairs on one PCR round used. Sensitivity of primers (at least one of the four primer pairs was positive) to HIV-2-seropositive samples was 100% (all nine) in Guinea-Bissau, 71% (12/17) in Côte d'Ivoire, 100% (all 20) in Gambian AIDS patients, and 85% (17/20) in Gambian pregnant women. Doubling the PBMC of dually seroreactive individuals from 7.5 x 10(4) to 1.5 x 10(5) in the PCR revealed the presence of both HIV-1 and 2 proviral DNA in 72% (92/127) in Côte d'Ivoire and 72% (59/82) in The Gambia. By doubling the number of PBMC, HIV-2 detection in dually seroreactive individuals by PCR was increased from 65 to 77% in Côte d'Ivoire and from 67 to 83% in The Gambia. CONCLUSIONS: The use of 1.5 x 10(5) primary uncultured PBMC and the newly designed HIV-2 primer pairs allowed us to document the highest percentage (72%) ever reported of HIV-1-HIV-2 dual infections amongst HIV-1-HIV-2 dually seroreactive individuals in Côte d'Ivoire and The Gambia. Improved detection of HIV-2 proviral DNA, rather than exposure to both viruses, infection with only one virus, or infection with a unique third virus containing epitopes common to both HIV-1 and HIV-2, contributes to a more accurate monitoring of the prevalence of HIV-1-HIV-2 dual infections.

DNA Primers↗

Acute and long-term changes in T-lymphocyte subsets in response to clinical and subclinical measles. A community study from rural Senegal.

To investigate the possibility of long-term suppression of T-lymphocyte subsets, we examined children exposed to measles at home during an epidemic in rural Senegal, at time of exposure and 1 and 6 months later. The measles case fatality ratio was 1%. Subclinical measles was common among vaccinated children exposed to measles (45%). Both clinical and subclinical cases of measles showed a significant rise in absolute CD4 count in the incubation period. In the prodromal phase and the first week after the rash, the lymphocyte percentage, the white blood cell count and the absolute CD4 cell numbers were significantly reduced. There was no persistent decrease of absolute CD4 or CD8 numbers at 1 or 6 months after exposure. Measles infection was followed by significant changes in the subset composition, both CD4 and CD8 percentages being significantly higher in the second month after measles than among non-seroresponders. These changes were more marked among girls, since they had significantly higher CD4 percentages and CD4/CD8 ratios than boys in the convalescence phase. In conclusion, measles infection is not associated with a long-term suppression of CD4+ or CD8+ T-lymphocytes.

Adolescent↗

Causes of mortality in twins in a rural region of The Gambia, West Africa.

Little is known about birth or mortality rates of twins in The Gambia. There are no reports of the causes of death among twins in sub-Saharan Africa. We identified twin births and deaths from a community-based study which had been carried out in a large rural region of The Gambia over a 5-year period from 1989 to 1993. The overall twinning rate excluding stillbirths was 14.3 (95% CI 12.9, 15.8) per 1000 live deliveries. This was significantly lower among the Mandinka ethnic group (8.8 per 1000) than among the Serahulis (15.1 per 1000) or Fulas (18.3 per 1000). The early-neonatal, late-neonatal and post-neonatal twin mortality rates were 114.0, 45.9 and 64.2 per 1000 live twin births, respectively. In comparison, the early-neonatal, late-neonatal and post-neonatal mortality rates of singletons were 18.6, 16.0 and 41.1 per 1000, respectively. In the post-neonatal period, malnutrition was more frequently a cause of death among twins than among singletons (7.8 per 1000 twin births vs 2.0 per 1000 singleton births; p = 0.0008). Appropriate strategies for preventing malnutrition are required for this high-risk group.

Birth Rate↗

The clinical spectrum of respiratory syncytial virus disease in The Gambia.

BACKGROUND: Respiratory syncytial virus (RSV) is a well-recognized cause of lower respiratory tract infections in early childhood in industrialized countries, but less is known about RSV infection in developing countries. METHODS: Four outbreaks of RSV infection that occurred between 1993 and 1996 in The Gambia, West Africa, were studied. RSV was sought by immunofluorescent staining of nasopharyngeal aspirate samples among young children who presented with respiratory infections at three hospitals in the Western Region of the country. RESULTS: Five hundred seventy-four children with RSV infection were identified. The median ages of children seen in 1993 through 1996 were 3, 7, 8 and 5 months, respectively. Sixty-two percent of children <6 months old were boys. Thirteen children (2.4%) had conditions considered to increase the risk of severe RSV infection. On physical examination crepitations were heard in 80% of the children admitted to hospital, whereas wheezes were heard in only 39%. Eighty (16%) children received oxygen because of hypoxemia. Nine of 255 blood cultures (3.5%) were positive: 4 Streptococcus pneumoniae; 2 Haemophilus influenzae type b; 2 Staphylococcus aureus; and 1 Enterobacter agglomerans. Thirteen children died (2.4%). During the 4 study years 90, 25, 75 and 95% of isolates typed were RSV Subgroup A, respectively. CONCLUSIONS: RSV is a significant cause of lower respiratory tract infection in young children in The Gambia, causing epidemics of bronchiolitis. It poses a significant burden on the health system, especially through the demand for supplementary oxygen. The clinical spectrum of RSV disease in The Gambia is similar to that seen in developed countries; concomitant bacterial infections are uncommon.

Developing Countries↗

Mortality among human immunodeficiency virus type 2-positive villagers in rural Guinea-Bissau is correlated with viral genotype.

We present the results of a 6-year study of 131 human immunodeficiency virus (HIV) type 2 (HIV-2)-infected individuals from a rural population in Guinea-Bissau. Proviral DNA sequences 1.3 kb in length were obtained from each individual and, together with clinical data, including proviral load and CD4 and CD8 levels, were used to assess whether viral genotype influences clinical outcome. With a phylogenetic model, a correlation was found between viral genotype and mortality; this correlation was not due to confounding factors, such as age-specific viral strains or cohabitation of patients. The data provide strong evidence for the involvement of viral genetic factors in determining HIV disease progression in vivo. The pattern of association found suggests that virulence factors are multiple and scattered throughout the HIV-2 genome and can be rapidly gained or lost by the virus through a combination of mutation and recombination. These findings may lead to the identification of viral determinants of HIV disease progression.

Adolescent↗

Cytotoxic T cells from human immunodeficiency virus type 2-infected patients frequently cross-react with different human immunodeficiency virus type 1 clades.

Knowledge of immune mechanisms responsible for the cross-protection between highly divergent viruses such as human immunodeficiency virus type 1 (HIV-1) and HIV-2 may contribute to an understanding of whether virus variability may be overcome in the design of vaccine candidates which are broadly protective across the HIV subtypes. We demonstrate that despite the significant difference in virus amino acid sequence, the majority of HIV-2-infected individuals with different HLA molecules possess a dominant cytotoxic T-cell response which is able to recognize HIV-1 Gag protein. Furthermore, HLA-B5801-positive subjects show broad cross-recognition of HIV-1 subtypes since they mounted a T-cell response that tolerated extensive amino acid substitutions within HLA-B5801-restricted HIV-1 and HIV-2 epitopes. These results suggests that HLA-B5801-positive HIV-2-infected individuals have an enhanced ability to react with HIV-1 that could play a role in cross-protection.

Cells, Cultured↗

A broad range of chemokine receptors are used by primary isolates of human immunodeficiency virus type 2 as coreceptors with CD4.

Like human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV), HIV-2 requires a coreceptor in addition to CD4 for entry into cells. HIV and SIV coreceptor molecules belong to a family of seven-transmembrane-domain G-protein-coupled receptors. Here we show that primary HIV-2 isolates can use a broad range of coreceptor molecules, including CCR1, CCR2b, CCR3, CCR4, CCR5, and CXCR4. Despite broad coreceptor use, the chemokine ligand SDF-1 substantially blocked HIV-2 infectivity of peripheral blood mononuclear cells, indicating that its receptor, CXCR4, was the predominant coreceptor for infection of these cells. However, expression of CXCR4 together with CD4 on some cell types did not confer susceptibility to infection by all CXCR4-using virus isolates. These data therefore indicate that another factor(s) influences the ability of HIV-2 to replicate in human cell types that express the appropriate receptors for virus entry.

Adaptation, Biological↗