To the Editor:
Highly active antiretroviral therapy (HAART) is used with increasing frequency in the Caribbean, which has the second highest prevalence of HIV infection in the world.1 There are no published data on the virologic or immunologic response to HAART in HIV-infected individuals from the English-speaking Caribbean. Barbados is a middle-income, developing, English-speaking Caribbean country, with a population of 260,000 and an estimated overall prevalence of HIV infection of 1.75%.2 Since 2002, HAART has been available to all HIV-infected individuals in Barbados free of cost, provided by the government through its health care delivery system. All HIV-infected adults in Barbados are followed up at a centralized HIV/AIDS care and treatment facility, the Ladymeade Reference Unit (LRU). We studied the virologic and immunologic response to HAART after 12 months of therapy in a population-based cohort of treatment-naive HIV-infected adults attending the LRU.
This is a prospective observational study. All treatment-naive HIV-positive adults in Barbados who attended the LRU clinic and were started on HAART between January 2002 and March 2003 were included in this study. All 3 classes of antiretroviral agents, including nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors (PIs), and nonnucleoside reverse transcriptase inhibitors (NNRTIs), were available at the LRU throughout the study. Patients started on HAART had baseline (measured less than 4 weeks before starting therapy) CD4 cell counts and viral load estimation. For all patients in the study, a complete profile of antiretroviral therapy was maintained prospectively, including the medications prescribed, the amount dispensed, the dose, and the prescription fill dates, along with other information on sociodemographic characteristics and clinical and health status elicited at the time of initial enrollment. After initiation of therapy, patients were scheduled for a follow-up visit at the LRU at 1 month, 2 months, and every 3 months thereafter for clinical and adherence assessment and for determination of CD4 cell count and viral load to assess the response to HAART. Participants' deaths were ascertained continuously using a combination of active surveillance methods and recorded during this 12-month study period. The virologic and immunologic responses to antiretroviral therapy in HIV-1-infected antiretroviral drug-naive adults were estimated by use of as-treated analyses. Data were analyzed using SPSS statistical software (SAS Institute, Cary, NC). Associations between categoric variables were assessed for statistical significance by the χ2 test. P ≤ 0.05 was considered to be statistically significant.
A total of 158 adults (median age = 39 years, 42.4% women) were started on HAART. Of the 92 male participants, 74 (80.4%) were heterosexual, 16 (17.4%) were homosexual, and 2 (2.2%) were bisexual. Among the 66 female participants, 1 was bisexual. None of these patients gave any history of intravenous illicit drug use; however, 19 (12%) patients gave a history of having smoked marijuana. Eighty-seven (53.2%) had an AIDS-defining illness at the time of starting HAART. Of these, most (73 patients) had presented with opportunistic infections, including oropharyngeal and esophageal candidiasis (33 patients) and Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia (16 patients). Most (82.1%) of the patients were at an advanced stage of immunodeficiency at the start of therapy (CD4 <200 cells/μL). The median CD4 cell count at baseline (n = 156) was 74 cells/μL (interquartile range [IQR]: 22.2-176.7 cells/μL), and the viral load (n = 94) was 122,500 HIV copies/mL (IQR: 54,125-350,000 copies/mL). Most patients (n = 131 [82.9%]) were started on 2 NRTIs and 1 NNRTI, whereas a smaller proportion were administered 2 NRTIs and 1 PI (n = 25 [15.8%]). Two patients (1.4%) received a triple-NRTI regimen. The specific treatment regimens by drug class are summarized as follows: among the 131 patients on triple-NNRTI regimens, 129 received efavirenz (EFV) and only 2 received nevirapine (NVP); among the 25 patients on PI regimens, 13 received indinavir (IDV), 7 were on NFV, and 5 were on lopinavir/ritonavir (LPV/r); and both patients on triple-NRTI regimens were administered a combination of ZDV plus lamivudine (3TC) plus abacavir (ABC). The distribution of the nucleoside backbone across the 158 patients was: zidovudine (ZDV) plus 3TC (n = 132), stavudine (d4T) plus 3TC (n = 24), and d4T plus didanosine (ddI) (n = 2). The most frequently represented treatment regimen was ZDV plus 3TC plus EFV (n = 104). Overall, 110 (69.6%) persons had an adherence level greater than 90% throughout the study period.
The overall retention rate for the cohort at 12 months was 148 (93.7%). There were 2 deaths, 2 persons discontinued follow-up, and 6 persons did not have a viral load or CD4 cell count measured at baseline and/or at 12 months. One hundred forty-eight persons who completed 12 months of HAART were analyzed for the virologic and immunologic outcome using as-treated analysis. After 12 months of HAART, 79.7% (118 of 148 patients) had virologic success (viral load <50 copies/mL). Table 1 describes the univariate analysis of factors associated with virologic success (posttreatment viral load <50 copies/mL). Persons aged 40 years or older (85.9%), those on an NNRTI-based regimen (85.1%), and those with greater than 90% adherence to HAART (92.3%) were significantly more likely to achieve virologic success. One hundred thirty-eight patients had CD4 cell counts measured at baseline and at 12 months of HAART. Ninety-nine (71.7%) persons had an increase of at least 100 cells/μL over baseline value (immunologic success). The median increase in the CD4 cell count after 12 months of HAART was 165 cells/μL (IQR: 94-264 cells/μL). Female gender (80.3%) and greater than 90% adherence to HAART (70.4%) were statistically significantly associated with achieving immunologic success (Table 2).
This study of the Barbados cohort of HIV-infected persons is the first such report of the efficacy of HAART in a community-based setting from the English-speaking Caribbean. HIV-infected persons in Barbados who started HAART did so at an advanced stage of their illness. Although published data are scarce, late presentation is common in Barbados and in the wider Caribbean region, probably because of widespread stigmatization of People Living with HIV/AIDS (PLWHAs), leading to nondisclosure of their HIV status.3 Clinical trials have shown that HAART is able to reduce HIV plasma viral loads to undetectable levels in 70% to 90% of patients and to increase CD4 cell counts.4,5 Studies of HAART in community settings (ie, nonclinical trial situations) in developed and developing countries have been reported to be much less effective.6-8 The high rates of virologic and immunologic success with predominantly NNRTI-based regimens in this cohort are notable. Farmer et al9 demonstrated that community-based approaches to HIV treatment were successful in rural Haiti, with 86% of patients having undetectable viral loads after at least 6 months of therapy. In addition, several recent studies have shown a good response to HAART despite advanced disease status with low CD4 cell counts and a high viral load.10,11
Further follow-up of the cohort in this ongoing study should be useful in asses sing the durability of the excellent response at 12 months into therapy and long-term efficacy of HAART in adults with advanced HIV disease in a Caribbean population. Findings from this study should be taken into consideration when scaling up antiretroviral therapy for HIV-infected adults in the Caribbean countries, where people often present late in the course of their illness.
Alok Kumar, MD*
Krishna R. Kilaru, MD†
Namrata Sippy, MSc†
Anne O. Carter, MD*
Timothy C. Roach, FRCP†
*School of Clinical Medicine and Research University of West Indies (Cave Hill), and Queen Elizabeth Hospital, Martindales Road St. Michael, Barbados †Ladymeade Reference Unit Ministry of Health Barbados
2. Caribbean Epidemiology Centre (CAREC)/PAHO/WHO. Status and Trends: Analysis of the Caribbean HIV/AIDS Epidemic 1982-2002
. CAREC, Port of Spain, Trinidad and Tobago. 2004:43.
3. Kilaru KR, Kumar A, Sippy N. CD4 cell counts in adults with newly diagnosed HIV infection in Barbados. Rev Panam Salud Publica
4. Hammer SM, Squires KE, Hughes MD, et al. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. N Engl J Med
5. Montaner JS, Reiss P, Cooper D, et al. A randomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients: the INCAS Trial. Italy, The Netherlands, Canada and Australia Study. JAMA
6. Djomand G, Roels T, Ellerbrock T, et al. Virologic and immunologic outcomes and programmatic challenges of an antiretroviral treatment pilot project in Abidjan, Cote d'Ivoire. AIDS
7. Coetzee D, Hildebrand K, Boulle A, et al. Outcomes after two years of providing antiretroviral treatment in Khayelitsha, South Africa. AIDS
8. Mocroft A, Devereux H, Kinloch-de-Loes S, et al. Immunological, virological and clinical response to highly active antiretroviral therapy treatment regimens in a complete clinic population. Royal Free Centre for HIV Medicine. AIDS
9. Farmer P, Léandre F, Mukherjee JS, et al. Community-based approaches to HIV treatment in resource-poor settings. Lancet
10. Phillips AN, Staszewski S, Weber R, et al. Swiss HIV Cohort Study; Frankfurt HIV Clinic Cohort; EuroSIDA Study Group. HIV viral load response to antiretroviral therapy according to the baseline CD4 cell count and viral load. JAMA
© 2005 Lippincott Williams & Wilkins, Inc.
11. Wood E, Hogg RS, Yip B, et al. Is there a baseline CD4 cell count that precludes a survival response to modern antiretroviral therapy? AIDS