Simple markers for initiating antiretroviral therapy among HIV-infected Ethiopians.

BACKGROUND: We explored the relevance of simple markers (clinical or laboratory markers not requiring sophisticated laboratories) in the decision of initiation of therapy in resource-poor settings. METHODS: Among HIV-infected Ethiopian cohort participants, simple markers predicting short-term death were examined using time-dependent Cox proportional hazards models. Timing of hypothetical treatment was compared between guidelines using the simple markers (based on presence of at least one marker), guidelines recommended by the United States Department of Health and Human Services (based on CD4 cell count and viral load), and guidelines for resource-limited settings recommended by the World Health Organization (WHO). RESULTS: From February 1997 to August 2001, 35 deaths were recorded among 155 HIV-positive participants. Simple independent predictors of death were low body mass index, HIV-related conditions, anaemia, and lymphocyte count < 1500 x 106/l. In such time as was covered by our study, 135 (87%) of 155 cohort participants would have had the same management under both the simple markers and the DHHS guidelines, i.e., would have been treated (n = 114, 74%) or not treated (n = 21, 14%). Of the 114 participants hypothetically treated under either set of guidelines, 91 (80%) would have started treatment at the same time. Application of the WHO guidelines for resource-limited settings (without CD4 cell counts) would have resulted in 11 participants dying without ever meeting a treatment indication during regular follow-up visits. CONCLUSION: Simple markers for the initiation of highly active antiretroviral therapy were identified among HIV-infected Ethiopian patients. The validity of these markers for monitoring patients' improvement following therapy remains to be evaluated.

Overall HIV-1 prevalence in pregnant women over-estimates HIV-1 in the predominantly rural population of Afar Region.

The appropriateness of sentinel sero-surveillance based upon ante-natal clinic (ANC) attendees to estimate HIV-1 prevalence in the general population has been questioned. In Ethiopia, where the population is heterogeneous and where economic and practical barriers to ANC attendance exist, problems of extrapolation may be exacerbated. We planned an unlinked anonymous sero-survey which included data on basic population characteristics to investigate whether sero-surveillance data from ANCs in Afar Region might be taken to represent the situation among the general population of the Region. 371 pregnant women attending Dubti Hospital and Assayta Health Centre were tested for HIV-1 (using a single ELISA test) and active syphilis (RPR test). Socio-demographic characteristics were collected for each woman. Of the women tested, 278 (75%) were 28 years of age or younger. Two hundred eighty (76%) were urban residents and 237 (64%) described themselves as being of Amhara ethnicity. Overall, 73 (19.7%) were HIV-1 positive, but prevalence was three times higher among the 237 women of Amhara ethnicity compared to the 112 of Afar ethnicity (24.9% vs 8.0%, p < 0.001), and almost three times higher for urban compared to rural residents (23.2% vs 8.8%, p < 0.001). Positive RPR results were strongly associated with HIV-1 infection (OR 3.37, 95% CI 1.47-7.71). According to the Demographic and Health Survey (DHS) 2000, only 4.5% of the population of Afar Region is of Amhara ethnicity, and 7.8% urban residents. We have demonstrated that basing ANC sero-surveillance in urban areas of Afar Region over-samples urban residents of Amhara ethnicity and yields a major over-estimation of overall HIV-1 prevalence for the Region. Reliable estimation of HIV-1 prevalence in Afar Region will require more flexible strategies that permit sampling of rural Afar residents.

Simple markers for initiating antiretroviral therapy among HIV-infected Ethiopians.

BACKGROUND: We explored the relevance of simple markers (clinical or laboratory markers not requiring sophisticated laboratories) in the decision of initiation of therapy in resource-poor settings. METHODS: Among HIV-infected Ethiopian cohort participants, simple markers predicting short-term death were examined using time-dependent Cox proportional hazards models. Timing of hypothetical treatment was compared between guidelines using the simple markers (based on presence of at least one marker), guidelines recommended by the United States Department of Health and Human Services (based on CD4 cell count and viral load), and guidelines for resource-limited settings recommended by the World Health Organization (WHO). RESULTS: From February 1997 to August 2001, 35 deaths were recorded among 155 HIV-positive participants. Simple independent predictors of death were low body mass index, HIV-related conditions, anaemia, and lymphocyte count < 1500 x 10(6)/l. In such time as was covered by our study, 135 (87%) of 155 cohort participants would have had the same management under both the simple markers and the DHHS guidelines, i.e., would have been treated (n = 114, 74%) or not treated (n = 21, 14%). Of the 114 participants hypothetically treated under either set of guidelines, 91 (80%) would have started treatment at the same time. Application of the WHO guidelines for resource-limited settings (without CD4 cell counts) would have resulted in 11 participants dying without ever meeting a treatment indication during regular follow-up visits. CONCLUSION: Simple markers for the initiation of highly active antiretroviral therapy were identified among HIV-infected Ethiopian patients. The validity of these markers for monitoring patients' improvement following therapy remains to be evaluated.

HIV-1 Subtype C gag-specific T-cell responses in relation to human leukocyte antigens in a diverse population of HIV-infected Ethiopians.

Knowledge of the most dominant T-cell epitopes in the context of the local human leukocyte antigen (HLA) background is a prerequisite for the development of an effective HIV vaccine. In 100 Ethiopian subjects, 16 different HLA-A, 23 HLA-B, and 12 HLA-C specificities were observed. Ninety-four percent of the population carried at least 1 of the 5 most common HLA-A and/or HLA-B specificities. HIV-specific T-cell responses were measured in 48 HIV-infected Ethiopian subjects representing a wide range of ethnicities in Ethiopia using the interferon (IFN)-gamma enzyme-linked immunospot (Elispot) assay and 49 clade C-specific synthetic Gag peptides. Fifty-eight percent of the HIV-positive study subjects showed T-cell responses directed to 1 or more HIV Gag peptides. Most Gag-specific responses were directed against the subset of peptides spanning Gag p24. The breadth of response ranged from 1 to 9 peptides, with most (78%) individuals showing detectable responses to <3 Gag peptides. The magnitude of HIV-specific T-cell responses was not associated with HIV viral load but correlated positively with CD4 T-cell counts. The most frequently targeted Gag peptides overlapped with those previously described for HIV-1 subtype C-infected southern Africans, and therefore can be used in a multiethnic vaccine.

Immunophenotyping of blood lymphocytes at birth, during childhood, and during adulthood in HIV-1-uninfected Ethiopians.

To obtain more insight into blood lymphocyte subpopulations of Ethiopians, we studied the immunologic profile of children and neonates and compared these data with those obtained from adults. Peripheral blood mononuclear cells (PBMCs) and cord blood mononuclear cells (CBMCs) were collected from 137 HIV-1-uninfected subjects aged 0 (cord blood) up to 40 years. Lymphocyte subsets (T, B, and NK cells, CD4+ and CD8+ T cells) were determined and T cell activation (CD38 and HLA-DR) and differentiation (CD45RO and CD27) markers were measured on CD4+ and CD8+ T cells. The absolute number and percentage values of most lymphocyte subpopulations differed substantially with age. Neonates and children were found to have significantly higher CD4+ T cell counts compared to adults. The median absolute CD4 count at birth was comparable to those reported for Caucasians. At birth 97% of the CD4+ T cells were naîve and this proportion significantly declined to 14.2% during adulthood. In addition, activation of both CD4+ and CD8+ T cells, as determined by the double expression of HLA-DR and CD38, was observed in children under the age of 16 and adults, but not in neonates. A more differentiated phenotype (CD27-) was observed in adults compared to children for both CD4+ and CD8+ T cells. The immune alterations including the remarkably low CD4 count with highly depleted naîve phenotype and a persistently activated immune system seen in adult Ethiopians are not apparent at birth, but rather develop over time.