Grabowski M Kate, Serwadda David M, Gray Ronald H, Nakigozi Gertrude, Kigozi Godfrey, Kagaayi Joseph, Ssekubugu Robert, Nalugoda Fred, Lessler Justin, Lutalo Thomas, Galiwango Ronald M, Makumbi Fred, Kong Xiangrong, Kabatesi Donna, Alamo Stella T, Wiersma Steven, Sewankambo Nelson K, Tobian Aaron A R, Laeyendecker Oliver, Quinn Thomas C, Reynolds Steven J, Wawer Maria J, Chang Larry W
From the Department of Pathology (M.K.G., A.A.R.T.) and the Division of Infectious Diseases, Department of Medicine (O.L., T.C.Q., S.J.R., L.W.C.), Johns Hopkins School of Medicine, and the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health (M.K.G., R.H.G., J.L., X.K., A.A.R.T., O.L., T.C.Q., S.J.R., M.J.W., L.W.C.), Baltimore, and the Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda (O.L., T.C.Q., S.J.R.) - all in Maryland; and Rakai Health Sciences Program, Entebbe (M.K.G., D.M.S., R.H.G., G.N., G.K., J.K., R.S., F.N., T.L., R.M.G., F.M., N.K.S., A.A.R.T., S.J.R., M.J.W., L.W.C.), and Centers for Disease Control and Prevention (D.K., S.T.A., S.W.), Makerere University School of Public Health (D.M.S., F.M.), and Makerere University School of Medicine (N.K.S.), Kampala - all in Uganda.
N Engl J Med. 2017 Nov 30;377(22):2154-2166. doi: 10.1056/NEJMoa1702150.
To assess the effect of a combination strategy for prevention of human immunodeficiency virus (HIV) on the incidence of HIV infection, we analyzed the association between the incidence of HIV and the scale-up of antiretroviral therapy (ART) and medical male circumcision in Rakai, Uganda. Changes in population-level viral-load suppression and sexual behaviors were also examined.
Between 1999 and 2016, data were collected from 30 communities with the use of 12 surveys in the Rakai Community Cohort Study, an open, population-based cohort of persons 15 to 49 years of age. We assessed trends in the incidence of HIV on the basis of observed seroconversion data, participant-reported use of ART, participant-reported male circumcision, viral-load suppression, and sexual behaviors.
In total, 33,937 study participants contributed 103,011 person-visits. A total of 17,870 persons who were initially HIV-negative were followed for 94,427 person-years; among these persons, 931 seroconversions were observed. ART was introduced in 2004, and by 2016, ART coverage was 69% (72% among women vs. 61% among men, P<0.001). HIV viral-load suppression among all HIV-positive persons increased from 42% in 2009 to 75% by 2016 (P<0.001). Male circumcision coverage increased from 15% in 1999 to 59% by 2016 (P<0.001). The percentage of adolescents 15 to 19 years of age who reported never having initiated sex (i.e., delayed sexual debut) increased from 30% in 1999 to 55% in 2016 (P<0.001). By 2016, the mean incidence of HIV infection had declined by 42% relative to the period before 2006 (i.e., before the scale-up of the combination strategy for HIV prevention) - from 1.17 cases per 100 person-years to 0.66 cases per 100 person-years (adjusted incidence rate ratio, 0.58; 95% confidence interval [CI], 0.45 to 0.76); declines were greater among men (adjusted incidence rate ratio, 0.46; 95% CI, 0.29 to 0.73) than among women (adjusted incidence rate ratio, 0.68; 95% CI, 0.50 to 0.94).
In this longitudinal study, the incidence of HIV infection declined significantly with the scale-up of a combination strategy for HIV prevention, which provides empirical evidence that interventions for HIV prevention can have a population-level effect. However, additional efforts are needed to overcome disparities according to sex and to achieve greater reductions in the incidence of HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and others.).
为评估预防人类免疫缺陷病毒（HIV）的联合策略对HIV感染发病率的影响，我们分析了乌干达拉凯地区HIV发病率与抗逆转录病毒疗法（ART）推广及男性医学包皮环切术之间的关联。还研究了人群层面病毒载量抑制情况和性行为的变化。
1999年至2016年期间，在拉凯社区队列研究中，通过12次调查从30个社区收集数据，该研究是一项针对15至49岁人群的开放性、基于人群的队列研究。我们根据观察到的血清转化数据、参与者报告的ART使用情况、参与者报告的男性包皮环切术、病毒载量抑制情况和性行为来评估HIV发病率的趋势。
共有33937名研究参与者贡献了103011人次的随访。共有17870名最初HIV阴性的人接受了94427人年的随访；在这些人中，观察到931例血清转化。2004年引入了ART，到2016年，ART覆盖率为69%（女性为72%，男性为61%，P<0.001）。所有HIV阳性者中HIV病毒载量抑制率从2009年的42%上升到2016年的75%（P<0.001）。男性包皮环切术覆盖率从1999年的15%上升到2016年的59%（P<0.001）。报告从未开始性行为（即推迟首次性行为）的15至19岁青少年比例从1999年的30%上升到2016年的55%（P<0.001）。到2016年，HIV感染的平均发病率相对于2006年之前（即HIV预防联合策略推广之前）的时期下降了42%——从每100人年1.17例降至每100人年0.66例（调整后的发病率比为0.58；95%置信区间[CI]为0.45至0.76）；男性下降幅度更大（调整后的发病率比为0.46；95%CI为0.29至0.73），女性下降幅度为（调整后的发病率比为0.68；95%CI为0.50至0.94）。
在这项纵向研究中，随着HIV预防联合策略的推广，HIV感染发病率显著下降，这提供了经验证据，表明HIV预防干预措施可产生人群层面的效果。然而，需要进一步努力以克服性别差异，并实现HIV感染发病率的更大幅度降低。（由美国国立过敏与传染病研究所等资助。）
