Long-term antiretroviral treatment outcomes in seven countries in the Caribbean.

OBJECTIVES: To report long-term HIV treatment outcomes in 7 Caribbean countries. DESIGN: Observational cohort study. METHODS: We report outcomes for all antiretroviral therapy (ART) naive adult patients enrolled on ART from program inception until study closing for cohorts in Barbados, the Dominican Republic, Haiti, Jamaica, Martinique, Trinidad, and Puerto Rico. Incidence and predictors of mortality were analyzed by time-to-event approaches. RESULTS: A total of 8203 patients were on ART from 1998 to 2008. Median follow-up time was 31 months (interquartile range: 14-50 months). The overall mortality was 13%: 6% in Martinique, 8% in Jamaica, 11% in Trinidad, 13% in Haiti, 15% in the Dominican Republic, 15% in Barbados, and 24% in Puerto Rico. Mortality was associated with male gender [hazard ratio (HR), 1.58; 95% confidence interval (CI): 1.33 to 1.87], body weight (HR, 0.85 per 10 pounds; 95% CI: 0.82 to 0.89), hemoglobin (HR, 0.84 per g/dL; 95% CI: 0.80 to 0.88), CD4 cell count (0.90 per 50 CD4 cells; 95% CI: 0.86 to 0.93), concurrent tuberculosis (HR, 1.58; 95% CI: 1.25 to 2.01) and age (HR, 1.19 per 10 years; 95% CI: 1.11 to 1.28). After controlling for these variables, mortality in Martinique, Jamaica, Trinidad, and Haiti was not significantly different. A total of 75% of patients remained alive and in care at the end of the study period. CONCLUSIONS: Long-term mortality rates vary widely across the Caribbean countries. Much of the difference can be explained by disease severity at ART initiation, nutritional status, and concurrent tuberculosis. Earlier ART initiation will be critical to improve the outcomes.

HIV-1 epidemic in the Caribbean is dominated by subtype B.

BACKGROUND: The molecular epidemiology of HIV-1 in the Caribbean has been described using partial genome sequencing; subtype B is the most common subtype in multiple countries. To expand our knowledge of this, nearly full genome amplification, sequencing and analysis was conducted. METHODOLOGY/PRINCIPAL FINDINGS: Virion RNA from sera collected in Haiti, Dominican Republic, Jamaica and Trinidad and Tobago were reverse transcribed, PCR amplified, sequenced and phylogenetically analyzed. Nearly full genomes were completed for 15 strains; partial pol was done for 67 strains. All but one of the 67 strains analyzed in pol were subtype B; the exception was a unique recombinant of subtypes B and C collected in the Dominican Republic. Of the nearly full genomes of 14 strains that were subtype B in pol, all were subtype B from one end of the genome to the other and not inter-subtype recombinants. Surprisingly, the Caribbean subtype B strains clustered significantly with each other and separate from subtype B from other parts of the pandemic. CONCLUSIONS: The more complete analysis of HIV-1 from 4 Caribbean countries confirms previous research using partial genome analysis that the predominant subtype in circulation was subtype B. The Caribbean strains are phylogenetically distinct from other subtype B strains although the biological meaning of this finding is unclear.

HIV-1 epidemic in the Caribbean is dominated by subtype B.

BACKGROUND: The molecular epidemiology of HIV-1 in the Caribbean has been described using partial genome sequencing; subtype B is the most common subtype in multiple countries. To expand our knowledge of this, nearly full genome amplification, sequencing and analysis was conducted. METHODOLOGY/PRINCIPAL FINDINGS: Virion RNA from sera collected in Haiti, Dominican Republic, Jamaica and Trinidad and Tobago were reverse transcribed, PCR amplified, sequenced and phylogenetically analyzed. Nearly full genomes were completed for 15 strains; partial pol was done for 67 strains. All but one of the 67 strains analyzed in pol were subtype B; the exception was a unique recombinant of subtypes B and C collected in the Dominican Republic. Of the nearly full genomes of 14 strains that were subtype B in pol, all were subtype B from one end of the genome to the other and not inter-subtype recombinants. Surprisingly, the Caribbean subtype B strains clustered significantly with each other and separate from subtype B from other parts of the pandemic. CONCLUSIONS: The more complete analysis of HIV-1 from 4 Caribbean countries confirms previous research using partial genome analysis that the predominant subtype in circulation was subtype B. The Caribbean strains are phylogenetically distinct from other subtype B strains although the biological meaning of this finding is unclear.

Lessons from a multisite international trial in the Caribbean and South America of an HIV-1 Canarypox vaccine (ALVAC-HIV vCP1452) with or without boosting with MN rgp120.

BACKGROUND: The first multicenter, international National Institutes of Allergy and Infectious Diseases (NIAID)-sponsored HIV vaccine trial took place in Brazil, Haiti, Peru and Trinidad. This randomized, double-blind, placebo-controlled, phase 2 trial evaluated the safety and immunogenicity of a clade B-derived, live canarypox HIV vaccine, vCP1452. vCP1452 was administered alone or with a heterologous boost of MN rgp120 glycoprotein. The trial was pivotal in deciding whether these vaccines advanced to phase 3 efficacy trials. METHODS: Forty seronegative volunteers per site were randomized to ALVAC alone, ALVAC plus MN rgp120, or placebo in a 0, 1, 3, and 6 month schedule. Immunogenicity was assayed by chromium-release cytotoxic T lymphocyte (CTL) responses; interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot assays (ELISpot); lymphocyte proliferation assays (LPA); neutralization; and enzyme-linked immunosorbent assays (ELISA). RESULTS: Enrollment and follow-up were excellent. Both vaccines were well tolerated. Neutralizing antibody to the laboratory-adapted MN strain was detected. Cellular immune responses, as measured by CTL, ELISpot, and LPA, did not differ between vaccines and placebos. CONCLUSIONS: The observation of disappointing immunogenicity in this and a parallel domestic study has informed future vaccine development. Equally important, challenges to doing an integrated trial across countries, cultures, languages, and differing at-risk populations were overcome. The identification of specific safety, ethical, logistic, and immunological issues in this trial established the foundation for current larger international studies.

Rapid clearance of virus after acute HIV-1 infection: correlates of risk of AIDS.

OBJECTIVE: Our objective was to define early virologic and immunologic determinants of human immunodeficiency virus (HIV) type 1 disease progression among 22 case subjects with acute infection from the Trinidad Seroconvertor Cohort. METHODS: A linear segmented regression model was fitted to sequential quantitative virus load measurements. Parameters of virus kinetics during different phases of primary infection were correlated with clinical and immunologic end points, by use of Kaplan-Meier estimates and Cox regression. RESULTS: Ten individuals developed acquired immunodeficiency syndrome (AIDS)-defining events. In univariate analysis, progression to AIDS was associated with rate of initial HIV clearance (P=.002), virus load during set point (P=.008), and CD4(+) cell count during steady state (P=.04). In the multivariate analysis, a rapid rate of initial clearance was the sole independent predictor of subsequent progression to AIDS and was associated with a 92% reduction in the risk of AIDS. The rate of initial clearance is inversely correlated with the number of early symptoms (r=-0.66; P=.0008). However, symptoms did not predict subsequent risk of AIDS. CONCLUSION: Among a subset of patients, rapid clearance of plasma HIV-1 after peak viremia is associated with lower viral set point, prolonged virus suppression before loss of virologic control, and decreased risk of AIDS. These findings are consistent with the hypothesis that effective immune responses during the earliest phase of infection are important determinants of the subsequent natural history.

Improved classification of recent HIV-1 infection by employing a two-stage sensitive/less-sensitive test strategy.

Current serologic techniques for the classification of recent HIV-1 infection produce some misclassifications, and, together with the loss to follow-up of individuals, results in decreased enrollment of HIV-infected persons into appropriate intervention programs. We report on the development of a sensitive/less sensitive (S/LS) test strategy that includes a rapid assay to quickly identify persons most likely to have recent infection, followed by an enzyme immunoassay (EIA) with exquisite specificity. The Uni-Gold Recombigen HIV rapid assay (UG; Trinity Biotech, Dublin, Ireland) was procedurally-modified and calibrated as an LS test to differentiate recent (<133 days) from established HIV infections using 178 samples from persons with known dates of infection. This method correctly classified 83.0% of recent infections, but with a high misclassification rate of persons with established infection. By performing the rapid test followed by a modified S/LS EIA, the positive predictive value of the combined results for recent infections was increased to 100%. This two-stage testing algorithm can result in an increased efficiency for the enrollment of recent infection cases over a standard EIA S/LS method alone due to provisional enrollment during an initial testing visit, and because of an increased accuracy for identifying truly recent infections. We conclude that the rapid S/LS assay provides a tool for capturing recent infection cases quickly and is particularly valuable in resource-limited settings, and that the two-stage strategy provides a more accurate identification of persons with recent HIV infection.

Fourth-generation enzyme-linked immunosorbent assay for the simultaneous detection of human immunodeficiency virus antigen and antibody

The VIDAS HIV DUO Ultra, a fourth-generation immunoassay under development for the simultaneous detection of human immunodeficiency virus type 1 (HIV-1) p24 antigen and antibodies to HIV-1 and HIV-2, was evaluated. The enzyme-linked fluorescence immunoassay, performed on the automated VIDAS instrument, is claimed to detect early and established HIV infection. The assay was challenged with a total of 2,847 samples that included 74 members of 10 seroconversion panels, 9 p24 antigen-only-reactive members of a panel of group M clades, 503 consecutively collected samples from individuals seeking care in the University of Maryland Medical System, 1,010 samples from U.S. blood donors, 1,141 samples from patients in a high-incidence population in Trinidad, 83 samples from a clinic for sexually transmitted diseases in the Bahamas, 10 confirmed HIV-1 group O samples, and 16 confirmed HIV-2 samples from the Cote d'Ivoire. Reference tests were U.S. Food and Drug Administration-licensed HIV antibody screening, p24 antigen tests, HIV confirmatory assays, and the Roche Diagnostics Amplicor HIV-1 Monitor. The VIDAS HIV DUO Ultra demonstrated 100% sensitivity and 99.5% specificity overall, with a 99.7% specificity in low-risk individuals. The analytical sensitivity, as assessed by seroconversion panels and p24 antigen in samples, was equivalent to the sensitivity of the reference assays used to characterize these panels. The VIDAS HIV DUO Ultra is accurate, offers potential advantages over conventional HIV testing for time and cost savings, has walk-away capability, and correctly identifies both early and established HIV infections.

William Hillary and sprue in the Caribbean: 230 years later

Parasitic infestation as a cause of diarrhoea and malabsorption is well recognised. It may occur in heavy infestations with hookworm as reported by Sheehy in Puerto Rico and Giardia Lamblia as reported by Professor O'Donovan of Dublin. In hookworm and giardial infestations tissue invasion of the small intestine as been observed occasionally by Stronglyoides stercoralis has much greater potential in this respect. A spru-like syndrome caused by this parasite is not uncommon in the Caribbean islands, particularly in Jamaica, Trinidad and Tobago and Puerto Rico (AU)

Transmission of HTLV-1 and HIV among homosexual men in Trinidad

Risk for human T-cell lymphotropic virus type I (HTLV-I) and human immunodeficiency virus (HIV infection was evaluated in 100 homosexual or bisexual men from Trinidad. High seropositivity for HTLV-I (15 percent vs 2.4 percent in the general population) was linked to duration of homosexuality and numbers of partners, suggesting that HTLV-I, like HIV, can be transmitted by homosexual sex. Forty percent of homosexuals compared with 0.19 percent of the general population were seropositive for HIV, and sexual contact with US homosexual men and prior history of gonorrhea were major risk factors. The seroprevalence of HIV was three times higher than that for HTLV-I, suggesting that HIV is more efficiently transmitted, especially since HIV appears to have been recently introduced into Trinidad. Altered immune status was prominent in individuals infected with HIV and coinfected with HIV AND HTLV-I. Whether HIV/HTLV-I coinfection amplifies clinical effects is a hypothesis that will require further evaluation (AU)