AIDS RESEARCH AND HUMAN RETROVIRUSES Volume 18, Number 16, 2002, pp. 1167–1173 © Mary Ann Liebert, Inc. Low Level Viremia and High CD4% Predict Normal Survival in a Cohort of HIV Type-2-Infected Villagers NEIL BERRY, 1,2 SHABBAR JAFFAR, 3 MAARTEN SCHIM VAN DER LOEFF, 4 KOYA ARIYOSHI, 4,5 ELIZABETH HARDING, 4 PA TAMBA N’GOM, 4 FRANCISCO DIAS, 6 ANDREW WILKINS, 4 DOMINIC RICARD, 1 PETER AABY, 7 RICHARD TEDDER, 1 and HILTON WHITTLE 4 ABSTRACT A community-based study of human immunodeficiency virus type 2 (HIV-2) infection was conducted in a rural village in northern Guinea Bissau, West Africa to assess the relationship between plasma HIV-2 RNA levels, CD4 lymphocyte percentage, and survival over an 8-year period. The cohort of 133 HIV-2-infected in- dividuals and 160 HIV-uninfected controls enrolled in 1991 were followed up at home until 1998. Thirty-one (23%) HIV-2-infected and 24 (16%) HIV-uninfected individuals died over the follow-up period (mortality hazard ratio 1.7, 95% CI 1.0, 2.9; p 5 0.06). In HIV-2-infected individuals, the median HIV-2 RNA level was 347 copies/ml and the mean CD4% was 28.6. Both plasma viremia and CD4% were independent predictors of survival, with hazard ratios increasing by 1.6 (95% CI, 1.1, 2.3) for each log 10 increase of plasma viremia and 1.7 (1.1, 2.6) for each 10% decrease of CD4%. Infected subjects with a plasma viral load $ the median (347 copies/ml) and a CD4% # the mean (28.6%) had a mortality hazard ratio of 3.1 (95% CI 1.7, 5.8) com- pared to uninfected controls, whereas the remaining infected subjects had a mortality rate similar to unin- fected controls, the mortality hazard ratio being 1.0 (95% CI, 0.5, 2.1.) In those who survived between 1991 and 1996, HIV-2 RNA levels were unchanged overall and CD4 lymphocyte counts remained high. In conclu- sion, baseline HIV-2 RNA levels predicted a normal survival for the majority, with low and stable levels of plasma viremia characterizing HIV-2 infections in this rural West African community. 1167 INTRODUCTION H UMAN LENTIVIRAL INFECTION, which today affects over 34 million persons, is caused by two related but distinct viruses, human immunodeficiency viruses types 1 and 2 (HIV- 1 and HIV-2), which differ in their natural history, level of viremia, transmission rates, and disease associations. 1–3 In Guinea-Bissau the prevalence of HIV-2 among adults is esti- mated to be about 8%. 3 A cohort study conducted in the capi- tal, Bissau Town, showed that the mortality rate among HIV- 2-infected subjects was 2.6 per 100 person-years, which was just over twice that among HIV-uninfected individuals. 4 In con- trast, a number of community-based studies from East Africa suggest that the mortality rate among HIV-1-infected individ- uals is over 10-fold greater than that of HIV-uninfected indi- viduals. 5,6 The factors that influence survival in HIV-infected African people and the reasons why survival appears to be much better in HIV-2 than in HIV-1 infections are not fully under- stood. In studies of HIV-1 conducted in developed countries, plasma viremia and CD4 cell count are important predictors of disease progression and survival. 7–9 They are now central to the effective management and the counseling of HIV-1-infected persons and are often used as primary end points in trials eval- 1 Department of Virology, Royal Free and University College Medical School, London, UK. 2 Division of Retrovirology, National Institute for Biological Standards and Control, South Mimms, Herts, UK. 3 Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK. 4 Medical Research Council Laboratories, Banjul, The Gambia, West Africa. 5 AIDS Research Centre, National Institute of Infectious Diseases, Tokyo, Japan. 6 Laboratório Nacional de Saude Publica, MINSAP, Bissau, Guinea-Bissau, West Africa. 7 Department of Epidemiology Research, Danish Epidemiology Centre, Statens Serum Institut, Copenhagen, Denmark.