Possible protective effect of HIV-2 against incident HIV-1 infection: review of available epidemiological and in vitro data.
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Publications and source records attributed to A E Greenberg.
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OBJECTIVE: To compare the seroincidence of HIV infection among female sex workers in Abidjan, Côte d'Ivoire before and during an intervention study to control sexually transmitted diseases (STD) and to study the effect of two STD diagnosis and treatment strategies on the prevalence of STD and on the seroincidence of HIV infection. METHOD: A screening facility for STD and HIV had been available since October 1992 for female sex workers. From June 1994, women who were HIV seronegative or HIV-2 positive during the screening could enroll in the intervention study in which participants reported once a month to a confidential clinic where they received health education, condoms and STD treatment if indicated. Women in the study were randomized either to a basic STD diagnosis and treatment strategy, which included a gynecologic examination when symptomatic, or to an intensive strategy that included a gynecologic examination regardless of symptoms. An outcome assessment every 6 months included a gynecologic examination, HIV serology and laboratory tests for STD. RESULTS: Of 542 women enrolled in the study, 225 (42%) had at least one outcome assessment. The HIV-1 seroincidence rate during the intervention study was significantly lower than before the study (6.5 versus 16.3 per 100 person-years; P = 0.02). During the study, the HIV-1 seroincidence rate was slightly lower in the intensive than in the basic strategy (5.3 versus 7.6 per 100 person-years; P = 0.5). CONCLUSION: National AIDS control programs should consider adopting as policy the type of integrated approach used in this intervention study for HIV prevention in female sex workers.
Plasma levels of human immunodeficiency virus type 1 (HIV-1) RNA and markers of immune activation were compared among HIV-1-infected female sex workers (FSWs) with (n=112) and without (n=88) sexually transmitted diseases (STDs) in Abidjan, Côte d'Ivoire. After adjustment for CD4+ T cells, the median virus load was 2.5-fold higher among HIV-seropositive FSWs with STDs than among those without an STD (P=.053). Median virus load was higher for FSWs with a genital ulcer (P=.052) or gonorrhoea (P=.058) than for FSWs without any STD. Median levels of markers of immune activation (CD38 and HLA-DR on CD8+ T cells, soluble tumor necrosis factor-alpha receptor II, and beta(2)-microglobulin) tended to be elevated, albeit nonsignificantly, among FSWs in the STD group. These findings have important public health implications in elaborating strategies for decreasing disease progression and transmission of HIV among FSWs.
OBJECTIVE: To detect anti-HIV antibodies in cervicovaginal secretions of HIV-seronegative female sex workers and to evaluate whether the presence of these antibodies is associated with increased sexual exposure. METHODS: A cross-sectional study was carried out at a confidential clinic for female sex workers in Abidjan, Côte d'Ivoire. The participants were 342 HIV-seronegative female sex workers in whom a cervicovaginal lavage was collected. The main outcome measures were the detection of antibodies to HIV-1 in cervicovaginal lavages using an in-house and a commercial (Seradyn Sentinel; Calypte Biomedical Corporation, Berkeley, California, USA) enzyme immunoassay; the detection of semen in cervicovaginal lavages; and the assessment of epidemiological and biological markers of sexual exposure to HIV. RESULTS: Cervicovaginal anti-HIV antibodies were detected in 7.3 and 29.8% of women using in-house enzyme-linked immunosorbent assay (ELISA) and Seradyn Sentinel respectively. All cervicovaginal secretions found to be positive by in-house ELISA were also positive by Seradyn Sentinel. In a minority of women, ranging from 2.9% by in-house ELISA to 12.3% by Seradyn Sentinel, the anti-HIV antibodies were present in vaginal fluids that did not contain semen. Sexual exposure to HIV was similar in women with anti-HIV antibodies in their semen-free cervicovaginal secretions compared with women without anti-HIV antibodies in their cervicovaginal secretions. CONCLUSIONS: Cervicovaginal HIV-specific antibodies were detected in a minority of sexually exposed HIV-seronegative female sex workers in Abidjan. The lack of association between increased sexual exposure to HIV and presence of cervicovaginal HIV-specific antibodies suggests that the production of genital HIV-specific antibodies in exposed seronegative women depends on the ability of individual women to mount specific mucosal immunity to HIV antigens, the determinants of which are currently unknown.
To determine the impact of dual infection with HIV-1 and HIV-2 on HIV-1 viral load and markers of immune activation among HIV-seropositive FSWs in Abidjan, we analyzed blood samples obtained from consenting HIV-seropositive FSWs attending a confidential clinic between September 1996 and June 1997 in Abidjan. Among HIV-1 and HIV-2 dually seropositive FSWs, polymerase chain reaction (PCR) testing with HIV-1 and HIV-2 primers was used to differentiate between FSWs who were PCR positive only for HIV-1 and those positive for both HIV-1 and HIV-2 (dually infected). Of the 203 FSWs, 151 (74%) were HIV-1 seropositive only (median age, 26 years), 4 (2%) were HIV-2 seropositive, and 48 (24%) were dually seropositive (median age, 30 years). Of the 48 dually seropositive FSWs, 33 (69%) were dually infected and 15 (31%) were dually seropositive. Median CD4+ T cell counts per microliter were not significantly different among the three groups (525 for HIV-1 positive only, 502 for dually infected, and 416 for dually seropositive) (p = 0.14). Median viral load (log10 copies/ml) was not significantly different among the HIV-1-only FSWs (4.8 log10 copies/ml) compared with the 32 dually infected FSWs (4.6 log10 copies/ml) and 14 dually seropositive FSWs (4.7 log10 copies/ml; p = 0.95). Median levels of HLA-DR immune activation were increased in both CD4+ and CD8+ T cells for the dually infected (n = 27) FSWs compared with those infected with HIV-1 only (n = 123) (p = 0.019 and p = 0.01, respectively). Dual infection does not appear to influence levels of HIV-1 viral load in vivo. However, levels of HLA-DR are higher among FSWs dually infected with HIV-1 and HIV-2 than among those infected with HIV-1 only.
Limited data exist on the distribution of HIV-1 subtypes in Côte d'Ivoire. The aim of this study is to describe the distribution of genetic subtypes of HIV-1 strains in six regions of Côte d'Ivoire. In 1997, we consecutively collected blood from 172 HIV-1-infected patients from six regional tuberculosis treatment centers. Peripheral blood mononuclear cells (PBMCs) from these people were analyzed by a restriction fragment-length polymorphism (RFLP) assay that involves a sequential endonuclease digestion of a 297-base pair polymerase chain reaction (PCR) fragment; plasma samples were tested by a V3-loop peptide enzyme immunoassay (PEIA). DNA sequencing of the protease or env genes was performed on all samples discordant in the two assays as well as a random sample of the concordant subtyped samples. Of 172 specimens, 3 were PCR-negative, and 169 were putatively classified as subtype A by RFLP. The 3 PCR-negative samples were unequivocally subtyped A by PEIA. Of the 169 RFLP subtype A samples, 159 (94%) were subtyped A by PEIA. Of the 10 discordant samples, PEIA testing classified 3 as subtype C, 2 as D, and 5 as F. Sequencing of the env gene classified these samples as 1 subtype A, 4 Ds, and 5 Gs. Thus, 163 (95%) of the specimens were subtype A, 3 subtype D, 4 subtype G, 1 A/D, and 1 A/G (IbNG) circulating recombinant forms (CRF). In conclusion, most HIV-1-infected tuberculosis patients throughout the interior of Côte d'Ivoire are infected with HIV-1 subtype A, which are very likely the A/G (IbNG) CRF. The uniform distribution of this subtype makes Côte d'Ivoire a potential site for vaccine trials.
SETTING: Tuberculin skin test (TST) survey of health care workers (HCWs) in selected clinical services in Abidjan, Côte d'Ivoire. OBJECTIVE: To assess whether HCWs in Abidjan are at increased risk for occupationally acquired Mycobacterium tuberculosis infection. DESIGN: From October 1996 to January 1997, consenting HCWs from four services where tuberculosis (TB) prevalence among patients was high and two services where it was low were evaluated with a questionnaire, TST (including evaluation of anergy) and chest radiograph. RESULTS: Of the 512 participants, 405 (79%) had a TST reaction of > or =10 mm, eight (2%) were anergic, five (1%) had a radiograph compatible with TB, and two had confirmed TB. Using a cut-off of 10 mm, we found a higher prevalence of TST positivity in services with high TB prevalence than in those with low TB prevalence (92% vs 72%; odds ratio [OR] 4.3; 95% confidence interval [CI] 2.3-8.0]) and among HCWs with direct (87%; OR 2.9; 95%CI 1.6-5.1) and indirect patient contact (80%, OR 1.7; 95%CI 1.0-2.3) than among those with minimal patient contact (69%). CONCLUSION: These findings indicate that TST positivity among HCWs is related to level of exposure to TB patients, and suggest that HCWs in Abidjan are at risk for the nosocomial transmission of TB.
BACKGROUND: There is a high incidence of opportunistic infection among HIV-1-infected patients with tuberculosis in Africa and, consequently, high mortality. We assessed the safety and efficacy of trimethoprim-sulphamethoxazole 800 mg/160 mg (co-trimoxazole) prophylaxis in prevention of such infections and in decrease of morbidity and mortality. METHODS: Between October, 1995, and April, 1998, we enrolled 771 HIV-1 seropositive and HIV-1 and HIV-2 dually seroreactive patients who had sputum-smear-positive pulmonary tuberculosis (median age 32 years [range 18-64], median CD4-cell count 317 cells/microL) attending Abidjan's four largest outpatient tuberculosis treatment centres. Patients were randomly assigned one daily tablet of co-trimoxazole (n=386) or placebo (n=385) 1 month after the start of a standard 6-month tuberculosis regimen. We assessed adherence to study drug and tolerance monthly for 5 months and every 3 months thereafter, as well as rates of admission to hospital. FINDINGS: Rates of laboratory and clinical adverse events were similar in the two groups. 51 patients in the co-trimoxazole group (13.8/100 person-years) and 86 in the placebo group (25.4/100 person-years) died (decrease In risk 46% [95% CI 23-62], p<0.001). 29 patients on co-trimoxazole (8.2/100 person-years) and 47 on placebo (15.0/100 person-years) were admitted to hospital at least once after randomisation (decrease 43% [10-64]), p=0.02). There were significantly fewer admissions for septicaemia and enteritis in the co-trimoxazole group than in the placebo group. INTERPRETATION: In HIV-1-infected patients with tuberculosis, daily co-trimoxazole prophylaxis was well tolerated and significantly decreased mortality and hospital admission rates. Our findings may have important implications for improvement of clinical care for such patients in Africa.
OBJECTIVE: To assess whether HIV-2 infection protects against HIV-1 infection by comparing the rate of HIV-1 seroconversion among HIV-negative and HIV-2-seropositive women followed in a cohort study in Abidjan, Côte d'Ivoire. DESIGN: Prospective cohort study METHODS: HIV seroconversion was assessed in 266 HIV-seronegative, 129 HIV-1-seropositive, and 127 HIV-2-seropositive women participating in a closed cohort study of mother-to-child transmission of HIV conducted during 1990-1994. Participants were seen every 6 months, and blood samples were obtained. All blood samples were screened for HIV antibodies by enzyme immunoassay (EIA) and confirmed by line immunoassay (LIA) and Western blot. Among women who were HIV-seronegative at enrolment, seroconversion was defined as new EIA-reactivity confirmed on LIA and Western blot. Among HIV-1- or HIV-2-seropositive women, seroconversion to dual reactivity was defined as new dual reactivity on the LIA that was confirmed by reactivity on both HIV-1- and HIV-2-monospecific EIA. RESULTS: Five HIV-seronegative women became HIV-1-seropositive [seroconversion rate, 1.1 per 100 person-years; 95% confidence interval (CI), 0.3-2.5), and none became HIV-2-seropositive. No HIV-1-seropositive women became HIV-1/2 dually reactive, whereas six HIV-2-seropositive women acquired HIV-1 seroreactivity and thus became HIV-1/2 dually reactive (seroconversion rate 2.9 per 100 person-years; 95% CI, 1.1-6.3). HIV-2-seropositive women were more likely to acquire HIV-1 seroreactivity than were HIV-seronegative women (rate ratio, 2.7; 95% CI, 0.7-11.2), but this difference was not statistically significant (P>0.15). CONCLUSION: HIV-2 infection does not appear to protect against HIV-1 infection.
We have compared the performance of the NucliSens and the standard and modified HIV Monitor assays to quantify HIV-1 RNA plasma viral load in 12 tuberculosis patients infected with HIV-1 env subtype D (n = 3) and env subtype G (n = 9) in Ivory Coast. RNA was quantified in all nine subtype G specimens by the modified Amplicor HIV Monitor (mean, 4.6 log10 copies/ml; range, 3.1-6.3 log10/ml), in seven specimens by NucliSens (mean, 4.4 log10 copies/ml; range, 2.7-5.5 log10 copies/ml), and in 6 specimens by the standard Amplicor HIV Monitor assay (mean, 4.2 log10 copies/ml; range, 3.5-5.0 log10 copies/ml). All three subtype D samples were amplified by both the modified Amplicor HIV Monitor (mean, 4.5 log10 copies/ml; range, 3.8-5.1 log10 copies/ml) and NucliSens (mean, 3.8 log10 copies/ml; range, 2.8-5.0 log10 copies/ml); two samples were quantified by the standard Amplicor HIV Monitor assay (mean, 3.0 log10 copies/ml; range, 2.4-3.6 log10 copies/ml). Our preliminary results suggest that the modified Amplicor HIV Monitor can accurately quantify HIV-1 RNA viral load in persons infected with subtype D and G strains.
We analyzed the genetic variability and phylogenetic relationships among 28 HIV-2 strains collected from patients enrolled in an HIV epidemiologic study in Abidjan, Ivory Coast, during 1995-1996. Although both subtype A (n = 8; 29%) and subtype B (n = 20; 71%) were present in this sampling, the majority of infections were caused by subtype B viruses. These findings contrasted with the reported predominance of HIV-2 subtype A in other African countries. The broad genetic diversity identified among protease gene sequences for HIV-2 subtype A (6%; range 3-15%) and subtype B (7%; range, 2-12%), and their presence in Abidjan during the 1980s, document a long coexistence of two viral subtypes in Ivory Coast. Our data indicate that viruses of subtypes A and B have contributed to the HIV-2 epidemic in Ivory Coast.
BACKGROUND: In Africa, the risk of mother-to-child transmission of HIV-1 infection is high. Short-course perinatal oral zidovudine might decrease the rate of transmission. We assessed the safety and efficacy of such a regimen among HIV-1-seropositive breastfeeding women in Abidjan, Côte d'Ivoire. METHODS: From April, 1996, to February, 1998, all consenting, eligible HIV-1-seropositive pregnant women attending a public antenatal clinic in Abidjan were enrolled at 36 weeks' gestation and randomly assigned placebo or zidovudine (300 mg tablets), one tablet twice daily until the onset of labour, one tablet at onset of labour, and one tablet every 3 h until delivery. We used HIV-1-DNA PCR to test the infection status of babies at birth, 4 weeks, and 3 months. We stopped the study on Feb 18, 1998, when efficacy results were available from a study in Bangkok, Thailand, in which the same regimen was used in a non-breastfeeding population. FINDINGS: 280 women were enrolled (140 in each group). The median duration of the prenatal drug regimen was 27 days (range 1-80) and the median duration of labour was 7.5 h. Treatment was well tolerated with no withdrawals because of adverse events. All babies were breastfed. Among babies with known infection status at age 3 months, 30 (26.1%) of 115 babies in the placebo group and 19 (16.5%) of 115 in the zidovudine group were identified as HIV-1 infected. The estimated risk of HIV-1 transmission in the placebo and zidovudine groups were 21.7% and 12.2% (p=0.05) at 4 weeks, and 24.9% and 15.7% (p=0.07) at 3 months. Efficacy was 44% (95% CI -1 to 69) at age 4 weeks and 37% (-5 to 63) at 3 months. INTERPRETATION: Short-course oral zidovudine was safe, well tolerated, and decreased mother-to-child transmission of HIV-1 at age 3 months. Substantial efforts will be needed to ensure successful widespread implementation of such a regimen.
OBJECTIVE: To evaluate HIV serologic testing algorithms based on a combination of three enzyme linked immunosorbent assays (ELISA) for the confirmation of HIV infection in Abidjan, Côte d'Ivoire, where HIV-2 and HIV-1 non-B subtypes are prevalent. METHODS: A total of 1069 human sera with known serologic status, in addition to a seroconversion and low titer antibody panel were initially tested by six ELISA to determine the sensitivity, specificity and delta values of the assays. On the basis of the performance of the assays, three ELISA (Enzygnost, ICE 1.0.2, and Vironostika) were selected for use in a parallel and serial testing algorithm in analyzing 8283 consecutively collected sera. In the parallel testing algorithm, sera concordantly reactive or non-reactive by Enzygnost and ICE 1.0.2 were considered as true positive or true negative, respectively. In the serial algorithm, sera reactive by Enzygnost were retested by ICE 1.0.2. Sera with discordant results were tested by Vironostika, and the results was considered definitive. All reactive sera, plus a random sample of negative sera were tested for confirmation by Peptilav. In addition, a random sample of reactive sera was tested by Western blot. RESULTS: All ELISA had 100% sensitivity; specificities ranged from 96.8 to 100%. Positive and negative delta values of the ELISA were high (range, 6.89 to 46.07 and -2.05 to -5.75, respectively). Of the 8283 sera, 2054 were considered true positives and were correctly classified by the parallel testing algorithm (sensitivity, 100%). Of the 6229 true negative sera, 6226 were negative by the parallel testing algorithm (specificity, 99.95%). The sensitivity of the serial algorithm was 99.96%, and specificity was 99.95%. None of the 250 concordant ELISA-negative sera in the algorithm that were randomly tested in Peptilav was positive; similarly, all of the 103 concordant ELISA-positive sera were confirmed by Western blot. The three-ELISA algorithm resulted in reagent cost-savings of at least 50% compared with the Peptilav-based algorithm. CONCLUSION: These results suggest that a combination of ELISA using different principles or antigens in a serial or parallel algorithm is an efficient and cost-effective alternative to the standard algorithm in areas where HIV-1 and HIV-2 are prevalent.
To better understand the molecular epidemiology of HIV genetic diversity in Abidjan, Ivory Coast, we performed a genetic analysis of 170 HIV-1-seropositive specimens representing newly diagnosed tuberculosis patients (n = 143) and women monitored in a mother-to-child transmission cohort study (n = 27). Preliminary screening with RFLP presumptively classified 162 (95.3%) of these as subtype A. The envelope region of 108 specimens was subtyped by sequence analysis: 102 (94.4%) were subtype A, 2 (1.9%) were subtype D, and 4 (3.7%) were subtype G. Subtyping gag and env regions of the genome suggested that five of the six nonsubtype A isolates exhibited a potentially mosaic structure. A comparative phylogenetic analysis of HIV-1 subtype A C2V3 from 27 Ivory Coast and 21 Ugandan sequences revealed a striking clustering among Ivory Coast variants, and an independent segregation from Ugandan subtype A. Despite independent clustering with other subtype A specimens, limited variability of the V3 loop apex was observed; the globally predominant V3 motif, GPGQ, represented 90.1% of the HIV-1 strains. This study demonstrates that clade A is the predominant HIV-1 subtype in HIV-seropositive individuals in Abidjan, Ivory Coast and that these strains are phylogenetically distinct from other subtype A strains observed in East Africa.
OBJECTIVE: To explore whether HIV serostatus (HIV-1, HIV-2, and dual (HIV-D) reactivity) and CD4 cell count affect human papillomavirus (HPV) in two groups of women from Côte d'Ivoire. METHODS: We conducted a cross sectional study of two groups of women. One group had low numbers of lifetime sex partners (maternal women, n = 258) and were enrolled based on HIV serostatus. The other group had high numbers of sex partners (female sex workers, n = 278) and all consenting self identified sex workers were admitted to this study. We collected epidemiological and clinical data, and cervicovaginal lavage for HPV testing. RESULTS: The groups had different distributions of HIV seroreactivity, but the rates of HPV DNA detection were similar. Most of the HPV DNAs detected in both groups were high risk types. A strong association of high risk HPV DNA and HIV-1 seropositivity was found in both maternal women (adjusted odds ratio (OR) 7.5 (95% CI 3.2-17.4)) and in sex workers (OR 5.0 (2.1-12.0)). The maternal group also showed an association of high risk HPV DNA detection with HIV-2 (OR 3.7 (1.6-8.5)) and HIV-D (OR 12.7 (4.3-37.5)) that was not observed in the sex workers. In addition, the association of high risk HPV DNA with HIV-1 in the maternal group was independent of low CD4 cell count, while in the sex workers the association depended on CD4 cell counts < or = 500 x 10(6)/l. CONCLUSIONS: We found that an association between HPV and HIV varied depending on the sexual behaviour and CD4 cell count of the population examined.
OBJECTIVE: To explore whether HIV types 1 and 2 and CD4 cell count affect cervical neoplasia independent of human papillomavirus (HPV) in women with high or low numbers of sexual partners residing in Abidjan, Côte d'Ivoire. METHODS: The study population and methods are described in the companion paper. Additional methods include a Papanicolaou smear for cytological diagnosis and statistical analysis. RESULTS: In maternal women, both HIV-1 and high risk HPV were significant independent risk factors for squamous intraepithelial lesions (SIL) (adjusted odds ratio (OR) 11.0 (95% CI 1.1-112) and 5.4 (1.5-18.8), respectively). Only high levels of HPV DNA in the lavage were associated with SIL (OR 13.2 (3.6-47.8)) in the maternal group. In female sex workers, high risk HPV was significantly associated with SIL (OR 23.7 (4.4-126)); HIV seropositivity was not. Any positive level (high or low amounts) of HPV DNA was significantly associated with SIL in sex workers (ORs 15.9 (3.3-76) and 12.7 (3.6-44), respectively). There was no association of SIL with CD4 cell counts < or = 500 x 10(6)/l in HIV seropositive women from either group. CONCLUSION: HPV or HIV-1 infection independently affect cervical neoplasia in women with low numbers of sex partners.
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.
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