HIV prevalence and associated risk factors among individuals aged 13-34 years in Rural Western Kenya.

OBJECTIVES: To estimate HIV prevalence and characterize risk factors among young adults in Asembo, rural western Kenya. DESIGN: Community-based cross-sectional survey. METHODS: From a demographic surveillance system, we selected a random sample of residents aged 13-34 years, who were contacted at home and invited to a nearby mobile study site. Consent procedures for non-emancipated minors required assent and parental consent. From October 2003 - April 2004, consenting participants were interviewed on risk behavior and tested for HIV and HSV-2. HIV voluntary counseling and testing was offered. RESULTS: Of 2606 eligible residents, 1822 (70%) enrolled. Primary reasons for refusal included not wanting blood taken, not wanting to learn HIV status, and partner/parental objection. Females comprised 53% of 1762 participants providing blood. Adjusted HIV prevalence was 15.4% overall: 20.5% among females and 10.2% among males. HIV prevalence was highest in women aged 25-29 years (36.5%) and men aged 30-34 years (41.1%). HSV-2 prevalence was 40.0% overall: 53% among females, 25.8% among males. In multivariate models stratified by gender and marital status, HIV infection was strongly associated with age, higher number of sex partners, widowhood, and HSV-2 seropositivity. CONCLUSIONS: Asembo has extremely high HIV and HSV-2 prevalence, and probable high incidence, among young adults. Further research on circumstances around HIV acquisition in young women and novel prevention strategies (vaccines, microbicides, pre-exposure prophylaxis, HSV-2 prevention, etc.) are urgently needed

An evaluation of HIV elite controller definitions within a large seroconverter cohort collaboration.

BACKGROUND: Understanding the mechanisms underlying viral control is highly relevant to vaccine studies and elite control (EC) of HIV infection. Although numerous definitions of EC exist, it is not clear which, if any, best identify this rare phenotype. METHODS: We assessed a number of EC definitions used in the literature using CASCADE data of 25,692 HIV seroconverters. We estimated proportions maintaining EC of total ART-naïve follow-up time, and disease progression, comparing to non-EC. We also examined HIV-RNA and CD4 values and CD4 slope during EC and beyond (while ART naïve). RESULTS: Most definitions classify ∼ 1% as ECs with median HIV-RNA 43-903 copies/ml and median CD4>500 cells/mm(3). Beyond EC status, median HIV-RNA levels remained low, although often detectable, and CD4 values high but with strong evidence of decline for all definitions. Median % ART-naïve time as EC was ≥ 92% although overlap between definitions was low. EC definitions with consecutive HIV-RNA measurements 90% of measurements <400 copies/ml over ≥ 10 years be used to define this phenotype

Molecular identification, cloning and characterization of transmitted/founder HIV-1 subtype A, D and A/D infectious molecular clones

AbstractWe report the molecular identification, cloning and initial biological characterization of 12 full-length HIV-1 subtype A, D and A/D recombinant transmitted/founder (T/F) genomes. T/F genomes contained intact canonical open reading frames and all T/F viruses were replication competent in primary human T-cells, although subtype D virus replication was more efficient (p<0.05). All 12 viruses utilized CCR5 but not CXCR4 as a co-receptor for entry and exhibited a neutralization profile typical of tier 2 primary virus strains, with significant differences observed between subtype A and D viruses with respect to sensitivity to monoclonal antibodies VRC01, PG9 and PG16 and polyclonal subtype C anti-HIV IgG (p<0.05 for each). The present report doubles the number of T/F HIV-1 clones available for pathogenesis and vaccine research and extends their representation to include subtypes A, B, C and D

Population-Based Biochemistry, Immunologic and Hematological Reference Values for Adolescents and Young Adults in a Rural Population in Western Kenya

BACKGROUND: There is need for locally-derived age-specific clinical laboratory reference ranges of healthy Africans in sub-Saharan Africa. Reference values from North American and European populations are being used for African subjects despite previous studies showing significant differences. Our aim was to establish clinical laboratory reference values for African adolescents and young adults that can be used in clinical trials and for patient management. METHODS AND FINDINGS: A panel of 298, HIV-seronegative individuals aged 13-34 years was randomly selected from participants in two population-based cross-sectional surveys assessing HIV prevalence and other sexually transmitted infections in western Kenya. The adolescent (/=18 years) ratio and the male-to-female ratio was 1ratio1. Median and 95% reference ranges were calculated for immunohematological and biochemistry values. Compared with U.S-derived reference ranges, we detected lower hemoglobin (HB), hematocrit (HCT), red blood cells (RBC), mean corpuscular volume (MCV), neutrophil, glucose, and blood urea nitrogen values but elevated eosinophil and total bilirubin values. Significant gender variation was observed in hematological parameters in addition to T-bilirubin and creatinine indices in all age groups, AST in the younger and neutrophil, platelet and CD4 indices among the older age group. Age variation was also observed, mainly in hematological parameters among males. Applying U.S. NIH Division of AIDS (DAIDS) toxicity grading to our results, 40% of otherwise healthy study participants were classified as having an abnormal laboratory parameter (grade 1-4) which would exclude them from participating in clinical trials. CONCLUSION: Hematological and biochemistry reference values from African population differ from those derived from a North American population, showing the need to develop region-specific reference values. Our data also show variations in hematological indices between adolescent and adult males which should be considered when developing reference ranges. This study provides the first locally-derived clinical laboratory reference ranges for adolescents and young adults in western Kenya

Triple-Antiretroviral Prophylaxis to Prevent Mother-To-Child HIV Transmission through Breastfeeding—The Kisumu Breastfeeding Study, Kenya: A Clinical Trial

Timothy Thomas and colleagues report the results of the Kisumu breastfeeding study (Kenya), a single-arm trial that assessed the feasibility and safety of a triple-antiretroviral regimen to suppress maternal HIV load in late pregnancy

HIV Incidence and Risk Factors for Acquisition in HIV Discordant Couples in Masaka, Uganda: An HIV Vaccine Preparedness Study

To determine the incidence of and risk factors for HIV acquisition in a cohort of HIV-uninfected partners from HIV discordant couples in Masaka, Uganda, and to establish its suitability for HIV vaccine trials.HIV-uninfected adults living in HIV discordant couple relationships were enrolled and followed for 2 years. Interviews, medical investigations, HIV counseling and testing, syphilis and urine pregnancy (women) tests were performed at quarterly visits. Sexual risk behaviour data were collected every 6 months.495 participants were enrolled, of whom 34 seroconverted during 786.6 person-years of observation (PYO). The overall HIV incidence rate [95% confidence interval (CI)] was 4.3 [3.1-6]; and 4.3 [2.8-6.4] and 4.4 [2.5-8] per 100 PYO in men and women respectively. Independent baseline predictors for HIV acquisition were young age [18-24 (aRR = 4.1, 95% CI 1.6-10.8) and 25-34 (aRR = 2.7, 95% CI 1.2-5.8) years]; alcohol use (aRR = 2.6, 95% CI 1.1-6); and reported genital discharge (aRR = 3.4, 95% CI 1.6-7.2) in the past year. Condom use frequency in the year preceding enrolment was predictive of a reduced risk of HIV acquisition [sometimes (aRR = 0.4, 95% CI 0.2-0.8); always (aRR = 0.1, 95% CI 0.02-0.9)]. In the follow-up risk analysis, young age [18-24 (aRR = 6.2, 95% CI 2.2-17.3) and 25-34 (aRR = 2.3, 95% CI 1.1-5.0) years], reported genital discharge (aRR = 2.5, 95% CI 1.1-5.5), serological syphilis (aRR 3.2, 95% CI 1.3-7.7) and the partner being ART naïve (aRR = 4.8, 95% CI 1.4-16.0) were independently associated with HIV acquisition. There were no seroconversions among participants who reported consistent condom use during the study.The study has identified important risk factors for HIV acquisition among HIV discordant couples. HIV-uninfected partners in discordant couples may be a suitable population for HIV vaccine efficacy trials. However, recent confirmation that ART reduces heterosexual HIV transmission may make it unfeasible to conduct HIV prevention trials in this population

Differences in HIV Natural History among African and Non-African Seroconverters in Europe and Seroconverters in Sub-Saharan Africa

Introduction It is unknown whether HIV treatment guidelines, based on resource-rich country cohorts, are applicable to African populations. Methods We estimated CD4 cell loss in ART-naïve, AIDS-free individuals using mixed models allowing for random intercept and slope, and time from seroconversion to clinical AIDS, death and antiretroviral therapy (ART) initiation by survival methods. Using CASCADE data from 20 European and 3 sub-Saharan African (SSA) cohorts of heterosexually-infected individuals, aged ≥15 years, infected ≥2000, we compared estimates between non-African Europeans, Africans in Europe, and Africans in SSA. Results Of 1,959 (913 non-Africans, 302 Europeans - African origin, 744 SSA), two-thirds were female; median age at seroconversion was 31 years. Individuals in SSA progressed faster to clinical AIDS but not to death or non-TB AIDS. They also initiated ART later than Europeans and at lower CD4 cell counts. In adjusted models, Africans (especially from Europe) had lower CD4 counts at seroconversion and slower CD4 decline than non-African Europeans. Median (95% CI) CD4 count at seroconversion for a 15–29 year old woman was 607 (588–627) (non-African European), 469 (442–497) (European - African origin) and 570 (551–589) (SSA) cells/µL with respective CD4 decline during the first 4 years of 259 (228–289), 155 (110–200), and 199 (174–224) cells/µL (p<0.01). Discussion Despite differences in CD4 cell count evolution, death and non-TB AIDS rates were similar across study groups. It is therefore prudent to apply current ART guidelines from resource-rich countries to African populations

CLSI-Derived Hematology and Biochemistry Reference Intervals for Healthy Adults in Eastern and Southern Africa

BACKGROUND: Clinical laboratory reference intervals have not been established in many African countries, and non-local intervals are commonly used in clinical trials to screen and monitor adverse events (AEs) among African participants. Using laboratory reference intervals derived from other populations excludes potential trial volunteers in Africa and makes AE assessment challenging. The objective of this study was to establish clinical laboratory reference intervals for 25 hematology, immunology and biochemistry values among healthy African adults typical of those who might join a clinical trial. METHODS AND FINDINGS: Equal proportions of men and women were invited to participate in a cross sectional study at seven clinical centers (Kigali, Rwanda; Masaka and Entebbe, Uganda; two in Nairobi and one in Kilifi, Kenya; and Lusaka, Zambia). All laboratories used hematology, immunology and biochemistry analyzers validated by an independent clinical laboratory. Clinical and Laboratory Standards Institute guidelines were followed to create study consensus intervals. For comparison, AE grading criteria published by the U.S. National Institute of Allergy and Infectious Diseases Division of AIDS (DAIDS) and other U.S. reference intervals were used. 2,990 potential volunteers were screened, and 2,105 (1,083 men and 1,022 women) were included in the analysis. While some significant gender and regional differences were observed, creating consensus African study intervals from the complete data was possible for 18 of the 25 analytes. Compared to reference intervals from the U.S., we found lower hematocrit and hemoglobin levels, particularly among women, lower white blood cell and neutrophil counts, and lower amylase. Both genders had elevated eosinophil counts, immunoglobulin G, total and direct bilirubin, lactate dehydrogenase and creatine phosphokinase, the latter being more pronounced among women. When graded against U.S. -derived DAIDS AE grading criteria, we observed 774 (35.3%) volunteers with grade one or higher results; 314 (14.9%) had elevated total bilirubin, and 201 (9.6%) had low neutrophil counts. These otherwise healthy volunteers would be excluded or would require special exemption to participate in many clinical trials. CONCLUSIONS: To accelerate clinical trials in Africa, and to improve their scientific validity, locally appropriate reference ranges should be used. This study provides ranges that will inform inclusion criteria and evaluation of adverse events for studies in these regions of Africa

Haematological and biochemistry laboratory abnormalities associated with splenomegaly in asymptomatic adults in Masaka, Uganda: implications for HIV biomedical prevention trials.

OBJECTIVES: To assess the degree of haematological and biochemistry abnormalities associated with splenomegaly in asymptomatic adults in order to determine whether they may be eligible for inclusion in HIV biomedical prevention trials. METHODS: Asymptomatic adults (50% women) aged 18-60 with splenomegaly (>or=grade II by Hackett's classification) who agreed to provide blood and urine specimens for laboratory testing were invited to participate in a cross-sectional study. Volunteers who were menstruating, pregnant, infected with HIV, syphilis or Hepatitis B and C, or had significant clinical findings were excluded. Haematological and biochemistry laboratory evaluations were performed for enrolled volunteers, and the results were compared to local reference ranges. The proportion of volunteers with out-of-range (OOR) values was estimated for each parameter. Linear regression models were fitted to investigate the association between grade of splenomegaly and laboratory values. RESULTS: The proportion of volunteers with OOR haematology values ranged from 4.5% (mean corpuscular volume) and 15% (CD4 cells) to 31% (basophils). Increasing spleen size was significantly associated with anaemia, thrombocytopenia and low CD4 count. OOR biochemistry values were found in about 10% of volunteers. Increasing spleen size was associated with reduced creatinine phosphokinase and creatinine (in men) and raised lactate dehydrogenase. CONCLUSIONS: In areas with a high prevalence of splenomegaly, most asymptomatic individuals with this condition have haematology and biochemistry values that fall within the local reference ranges, and they could therefore be eligible for inclusion in HIV biomedical prevention trials. However, the effect of splenomegaly on certain parameters should be taken into account during interpretation of laboratory-based adverse events