Key harm reduction interventions and their impact on the reduction of risky behavior and HIV incidence among people who inject drugs in low-income and middle-income countries.

PURPOSE OF REVIEW: HIV infection rates continue to rise among people who inject drugs (PWID) in many lower- and middle-income countries (LMICs). Although progress is being made in prevention and care for PWID in some settings, coverage of essential services remains low. This article reviews the evidence for the benefits of scaling up key interventions as a combination prevention and treatment package for PWID. RECENT FINDINGS: WHO defined a comprehensive package of nine interventions for PWID, of which the following four have evidence for effectiveness in reducing HIV incidence: needle and syringe programs (NSP), medication-assisted therapy (MAT), antiretroviral therapy (ART), and HIV counseling and testing (HCT). Coverage of these interventions among PWID in LMICs varies from low (≤20%) to medium (>20-60%). At least a 60% coverage is likely to be required to reduce HIV incidence. Evidence from LMIC contexts suggests that NSP and MAT can reduce high-risk injecting behavior, HCT can reduce risky sexual behavior and ART can plausibly have preventive benefit among PWID for onward parenteral transmission with clearer evidence that antiretroviral therapy (ARV) can prevent onward sexual transmission. Modeling analysis suggests that compared with current low coverage, a scale-up of these four interventions in combination would be a beneficial and cost-effective approach. SUMMARY: The continuation of significant HIV incidence among PWID in LMIC settings is avoidable with the implementation of immediate scale-up of key harm reduction and ARV treatment interventions. Policymakers should address the structural and resource allocation barriers to allow this scale-up to occur.

Tenofovir and abacavir combination therapy: lessons learned from an urban clinic population.

Regimens containing abacavir (ABC), tenofovir (TDF), and lamivudine (3TC) have recently been demonstrated to have high failure rates. This poses a clinical dilemma of how to manage patients currently being treated with other regimens containing tenofovir/abacavir. We evaluated the outcomes of tenofovir/abacavir regimens in our clinical practice through a retrospective review of 2655 charts. Two hundred patients (7%) were on a tenofovir/abacavir-containing regimen. Fifty-nine patients met the criteria for analysis and were grouped into three groups: (1) antiretroviral naïve, (2) virally suppressed patients switched to TDF/ABC, and (3) patients with failure of their first antiretroviral regimen. Rates of viral suppression in the naïve, switch, and first-failure groups were 95%, 86%, and 46%, respectively. In the first-failure group, viral suppression was 66% without and 18% with a preexisting M184V. A composite analysis of the groups revealed a success rate of 86% when the regimen contained zidovudine (ZDV) and 62% when it did not. No K65R mutations were noted. These findings support continued caution in the use of TDF/ABC in combination. However, these data suggest that this combination may be successfully used in selected situations such as in combination with ZDV. In patients already virally suppressed on a TDF/ABC-containing regimen, considerations include continuing the regimen or adding zidovudine, in the attempt to protect against the development of a K65R mutation and/or virologic failure, versus changing a stable regimen.

A simple and inexpensive particle agglutination test to distinguish recent from established HIV-1 infection.

OBJECTIVES: We sought to modify the Serodia HIV-1/HIV-2 particle agglutination assay (PA), a simple and cost-effective HIV assay that is used globally for the detection of HIV antibodies, as a sensitive/less sensitive test (S/LS) to identify recently infected individuals and to estimate HIV incidence. METHODS: The Serodia PA test was modified as an S/LS test (PA-LS) by using HIV antigen-coated gelatin particles at a dilution of 1:68 and a specific diluent, and calibrated using 37 HIV clade B seroconversion panels (309 samples) from Trinidad and from a commercial source that were tested at dilution intervals from 1:10 to 1:80,000. The greatest sensitivity for correctly classifying samples from recent and established infections was determined by receiver operator curve (ROC) analysis. RESULTS: At a 1:40,000 sample dilution and a days post-seroconversion cutoff of 190 days, the PA-LS test yielded a 97% sensitivity for classifying recent and established infection samples. Furthermore, at a 1:20,000 dilution, the positive predictive value for correctly identifying recently infected individuals was 99%. The PA-LS test offers a 30-44-fold cost saving over currently available S/LS tests. CONCLUSION: A modified, low cost and simple-to-perform PA test is appropriate for use in resource-limited countries, and has exhibited excellence in distinguishing recent from established HIV infection.

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.

Antenatal screening for HIV in North Trinidad. Demographic characteristics of patients, acceptability of testing and the rising prevalence of infection - Poster abstract

OBJECTIVE: To ascertain the acceptability of HIV screening in pregnancy and the prevalence of HIV in pregnant women in north Trinidad. DESIGN AND METHOD: All women attending an antenatal clinic at the Port of Spain General Hospital were offered HIV testing at booking. Written consent was obtained after testing counselling and blood samples were tested using an ELISA assay with positive results confirmed by western blot. Demographic data were also collected. HIV positive women/infant pairs were tested using a modified CDC - Thailand regime. RESULTS: A total of 338 new patients were seen between March and November 1999 of whom only 8 refused testing. Ten patients tested positive giving a prevalence of 3 percent. All of the HIV positive patients were of African or mixed race descent which reflected the population attending this clinic. CONCLUSION: Our data indicated a slowly rising prevalence of HIV in pregnant women in north Trinidad. The majority of patients (98 percent) easily accept screening.(AU)

Seroprevalence of human herpesvirus-8 (HHV-8) in countries of Southeast Asia compared to the USA, the Caribbean and Africa

Seroprevalence of HHV-8 has been studied in Malaysia, India, Sri Lanka, Thailand, Trinidad, Jamaica and the USA, in both healthy individuals and those infected with HIV. Seroprevalence was found to be low in these countries. In contrast, the African countries of Ghana, Uganda and Zambia showed high seroprevalences in both healthy and HIV-infected populations. This suggests that human herpes virus-8 (HHV-8) may be either a recently introduced virus or one that has extremely low infectivity. Nasopharyngeal and oral carcinoma patients from Malaysia, Hong Kong and Sri Lanka who have very high EBV titres to show that only 3/82 (3.7 percent) have antibody to HHV-8, demonstrating that there is little, if any, cross-relativity between antibodies to these two gamma viruses. (AU)

A study of adult T-cell leukemia/lymphoma incidence in central Brooklyn

Adult T-cell leukemia/lymphoma (ATL), a rare outcome of infection with human T-lymphotropic virus (HTLV-I), is endemic in central Brooklyn, which has a large Caribbean migrant population. Previous studies have suggested that HTLV-I prevalence in central Brooklyn may be similar to that recorded in the Caribbean islands. We established a pilot 1-year surveillance program to identify cases of ATL in 7 of 10 hospitals serving the residents of 18 zip codes of central Brooklyn with a combined population of 1,184,670. Of the 6,198 in-patient beds in the catchment area, approximately 83 percent were covered. Twelve incident cases of ATL were ascertained, all among persons of Afro-Caribbean descent, indicating an annual incidence in African-Americans in this community of approximately 3.2/100,000 person-years. Unexplained hypercalcemia was the most useful screening method, identifying 3 of 5 patients not referred for possible ATL by a local hematologist. The female:male ratio was 3:1. The age pattern was different from that reported in the Caribbean Basin and closer to the pattern seen in Japan. Our study supports evidence that HTLV-I infection and ATL are endemic in central Brooklyn and suggests that a more intensive surveillance program for this disease coupled with intervention efforts to reduce HTLV-I transmission are warranted.(Au)

The challenge of HIV/AIDS in the Caribbean at the dawn of a new millenium

The Caribbean region continues to experience an expanding HIV/AIDS epidemic. Population HIV-1 prevalence in this region is second only to that in sub-Saharan Africa, reaching 5-6 percent in Haiti and up to 3 percent in Guyana and the Bahamas. While AIDS deaths are declining in developed countries, death rates from AIDS have continued to rise in the Caribbean because of the general unavailability of newer combination therapies. Over the past decade we have witnessed the rapid transition from HIV-1/AIDS in so called risk groups such as gay men and intravenous drug users to spread within the general heterosexual community. This transition has been fuelled by the concurrence of factors which enhance HIV risk such as high rates of partner exchange and poorly or untreated concomitant sexually transmitted diseases, particularly ulcerative diseases. In countries such as Trinidad and the Bahamas an epidemic of crack cocaine use in the eighties provided a fertile milieu for rapid HIV transmission through sexual activity. Each Caribbean territory has its own version of the epidemic, but the commonalities are striking. At the dawn of a new millenium the region continues the struggle against HIV/AIDS in the face of the many problems of crumbling infrastructures a generation after independence, marginal economies, inadequate public engagement in the face of competing priorities, lack of treatment and inadequate research. Recent advances in HIV-I vaccine development may hold some promise for checking the major public health crisis facing the Caribbean at this time.(AU)

Direct and indirect estimates of HIV-1 incidence in a high prevalence population

While the worldwide AIDS epidemic continues to expand, directly measured incidence data are difficult to obtain. Methods to reliably estimate human immunodeficiency virus type 1 (HIV-1) incidence from more easily available data are particularly relevant in those parts of the world where prevalence is rising in heterosexually exposed populations. The authors set out to estimate HIV-1 incidence in a population of heterosexual sexually transmitted disease clinic attended in Trinidad who had a known high prevalence of HIV-1 subtype B. Over the period 1987-1995, HIV-1 incidence estimates from serial cross-sectional studies of HIV-1 prevalence, passive follow-up of clinic recidivists, modeling of early markers of HIV-1 infection (p24 antigen screening), and a cohort study of seronegative genital ulcer disease cases were compared. Measuring incidence density in the genital ulcer disease cases directly gave the highest estimate, 6.9 percent per annum. Screening for the detection of early HIV-1 markers yielded an incidence of 5.0 percent per annum, while estimating incidence from serial cross-sectional prevalence data and clinic recidivists gave estimates of 3.5 percent and 4.5 percent per annum, respectively. These results were found to be internally consistent. Indirect estimates of incidence based on prevalence data can give accurate surrogates of true incidence. Within limitations, even crude measures of incidence are robust enough for health planning and evaluation purposes. For planning vaccine efficacy trails, consistent conservative estimates may be used to evaluate population before targeting them to cohort studies(AU)

Incidence of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Jamaica and Trinidad

HTLV-I is sexually transmitted more efficiently from men to women than vice versa, and the majority of HTLV-I endemic areas report a female preponderance of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) cases. The objective of this study was to estimate the gender and age specific incidence rates of HAM/TSP in the general population as well as in the HTLV-I-infected population in Jamaica and Trinidad and Tobago. Incidence rates for HAM/TSP were computed based on all reported incident cases in both countries between 1990 and 1994. Population cenus reports for 1990 were used to calculate the population at risk. The age-standardized HAM/TSP incidence rate (mean +/- standard error of the mean) in Jamaica was 1.8 +/- 0.2/100,000 person years (PY). Among individuals of African descent in Trinidad and Tobago, the rate was 1.7 +/- 0.4/100,000 PY. As in HTLV-I seroprevalence, the incidence rate of HAM/TSP increased with age through the fifth decade of life and was three time as high in women than in men. The HAM/TSP incidence rate, calculated as a function of the number of HTLV-I infection persons in each age stratum, is higher in women (24.7/100,000 PY) than in men 17.3/100,000 PY). With HTLV-I infection, the lifetime risk of developing HAM/TSP was estimated to be 1.9 percent overall and is slightly higher in women (1.8 percent) than in men (1.3 percent). Thus, the higher prevalence of HTLV-I in women in endemic areas does not fully explain the preponderance of female HAM/TSP, suggesting that other cofactors must be present. The higher incidence rate in women between the ages of 40 and 59 years, as well as the increase in HAM/TSP incidence rates with age, are indicative of the importance of adult-acquired HTLV-I infection, presumably through sexual transmission(AU)

Comparison of HHV-6 antibody titers in West Africa and the Caribbean

Human herpesvirus-6 (HHV-6) infections seems to be ubiquitous early in life, but antibody responses vary by geographic area. We compared HHV-6 antibody titer in 123 West African and 122 Caribbean serum samples. A quantitative immunofluorescence assay (IFA) using antigens derived from an HSB-2 cell line was used to test for IgG HHV-6 (GS strain) antibodies. The prevalence of HHV-6 antibodies was high (98 percent) in both sites. African samples had a significantly higher geometric mean titer (GMT: 697) than did Caribbean samples (GMT: 99). There was no difference between males (GMT: 260) and females (GMT: 270) overall. Children up to and including 9 years old had significantly higher titers (GMT: 483) than did all others (GMT: 237), and female children tended to have higher titers than did male children. In both areas there was a trend towards highest titer at younger age, followed by a decrease in titer in the oldest age group. Environmental and host factors may explain these geographic differences in antibody responses between two groups of African origin. (AU)

Effect of human T-lymphotropic virus type I infection on non-Hodgkin's lymphoma incidence

We previously reported from a case-control analysis that T-cell non-Hodgkin's lymphoma (NHL) was strongly associated with human T-lymphomphotropic virus type I (HTLV-I) infection in Jamaica and Trinidad and that the relative risk for HTLV-I infection was very high in younger patients. Purpose: the objective of this study was to estimate the age-specific incidence rates of NHL among HTLV-I-infected and HTLV-I-uninfected adults in Jamaica and Trinidad. Methods: Population rates of HTLV-I infection were calculated from available census reports and serosurvey data. Incidence rates for NHL were calculated from all incident cases in Jamaica during 1984-1987 (n = 135) and from all incident cases in Trinidad during 1986-1990 (n = 117). Using biopsy material, we determined whether the immunophenotype or the tumor cells was T cell, B cell, or other. NHL incidence rates were computed according to HTLV-I status, age, sex, and tumor phenotype for each country separately and for both countries combined by weighting to the relative population size of each country. Results: The age-standardized NHL incidence rate (mean ñ SE) in Jamaica was 1.9 ñ 0.2 per 100,000 person-years (PY). In Trinidad, the rate was 2.9 ñ 0.4 per 100,000 PY. Overall, the incidence of NHL increased with age and was higher in males than in females. In the HTLV-I-infected population, the incidence of NHL was inversely related to age, and age-specific rates were higher in males than in females. The NHL incidence in those estimated to have acquired HTLV-I infection in childhood, however, showed no sex difference, and one in 1300 such carriers (95 percent confidence interval: one in 1100 to one in 1600) per annum were estimated to be at such risk. For T-cell NHL, as proxy for adult T-cell lymphoma/leukemia, incidence was highest in those patients infected with HTLV-I early in life (perinatally or via breast milk), with high, sustained risk from early adulthood in both sexes. Conclusions: While overall NHL incidence rates reveal that HTLV-I endemicity does not impose an exaggerated lymphoma burden on these populations, the risk for lymphoma among carriers who acquire infection early in life is dramatic and is consistent with the hypothesis that virus exposure early in life is most important for lymphomagenesis. Implications: Studies of HTLV-I carriers known to be infected in childhood may provide insight into markers intermediate in the lymphomagnetic process. Strategies to disrupt early-life transmission of HTLV-I, notably mother-infant transmission, may be critical in reducing the burden of lymphoreticular disease in these populations (AU)

Role of HTLV-I in development of non-Hodgkin lymphoma in Jamaica and Trinidad and Tobago. The HTLV lymphoma study group

Human T-cell lymphotropic virus type I (HTLV-I) has been implicated in the aetiology of adult T-cell leukaemia/lymphoma in Japan and elsewhere, particularly the Caribbean. We have carried out parallel case-control studies in Jamaica and in Trinidad and Tobago to quantify the role of HTLV-I in the development of non-Hodgkin lymphoma (NHL). 135 cases of NHL were enroled in Jamaica and 104 in Trinidad and Tobago. Controls were selected from patients treated in the same wards or clinics at the same time as the cases. Overall, patients with NHL were 10 times more likely than were controls to be seropositive for HTLV-I (Jamaica odds ratio 10.3 [95 percent CI 6.0-18.0], Trinidad and Tobago 14.4 [7.6-27.2]). In both countries the association between NHL and HTLV-I was greatest for T-cell lymphomas (18.3 [9.5-35.6] and 63.3 [25-267]). Among T-cell lymphomas especially, there was no significant difference between men and women in the association between NHL and HTLV-I, but there was a significant inverse relation between age and likelihood of HTLV-I seropositivity. B-cell lymphomas were predominant in the older age groups and were not associated with HTLV-I seropositivity. These findings are consistent with the hypothesis that early life exposure to HTLV-I is important for risk of subsequent ATL. Prevention of vertical transmission of HTLV-I could reduce by 70-80 percent cases of NHL in people under 60 years in this region (AU)

Retroviruses in the Caribbean

Transmission of HIV in many Caribbean countries has followed the pattern of initial predominance among homosexual and bisexual male, with the infection subsequently spreading into the heterosexual community. However, on Saint Lucia the epidemic began among heterosexual contacts of Saint Lucia labourers from Florida; in Bermuda 58 percent of AIDS cases have been in interavenous drug abusers; and in the infected via the perinanatal route. Seroprevalence of the human T-lymphotropic virus, type 1 (HTLV-), whose modes of transmission resemble those of HIV, has been found to range from 2.3 percent in Trinidad and Tobago to 5.4 percent in Jamaica. In a study of HIV and HTLV-1 infection patterns in homosexuals males in Trinidad and Tobago, the cohort was too small for confirmation that coinfection with these two viruses hastended progression to AIDS, but further investigation is warranted. (AU)

Cutaneous histoplasmosis in the acquired immune deficiency syndrome: a report of three cases from Trinidad

Three cases are reported of patients with the acquired immune deficiency syndrome (AIDS) and cutaneous histoplasmosis. Their initial presentation was that of a generalised malculopapular rash. Two patients were bisexual males and the third was an unmarried female. The range of opportunistic infections seen in AIDS patients in Trinidad is mentioned and clinicians are alerted to the fact that in areas endemic for histoplasma capsulatum maculopapular rash in patients with AIDS may suggest disseminated histoplasmosis. The value of skin biopsy is mentioned. (AU)