A Uganda study has provided real-world evidence that implementing a combination of proven HIV prevention measures across communities can substantially reduce new HIV infections in a population.
Investigators found that HIV incidence dropped by 42% among nearly 18,000 people in Rakai District, Uganda, during a seven-year period in which the rates of HIV treatment and voluntary medical male circumcision increased significantly.
The HIV prevention strategy whose impact was observed in the study is based on earlier findings by the National Institutes of Health (NIH) and others demonstrating the protective effect of voluntary medical male circumcision for HIV-uninfected men and of HIV-suppressing antiretroviral therapy (ART) for halting sexual transmission of the virus to uninfected partners. The strategy is also based on studies showing that changes in sexual behaviour, such as having only one sexual partner, can help prevent HIV infection.
"Before this study, we knew that these HIV prevention measures worked at an individual level, yet it was not clear that they would substantially reduce HIV incidence in a population – or even if it would be possible to get large numbers of people to adopt them," said Dr Anthony S Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH. "This new analysis demonstrates that scaling up combination HIV prevention is possible and can turn the tide of the epidemic."
NIAID co-funded the research, and NIAID investigators oversaw all laboratory operations. The President's Emergency Plan for AIDS Relief (PEPFAR) funded the provision of combination HIV prevention, including ART and circumcision services, during the period observed in the study.
The newly reported research involved nearly 34,000 people ages 15 to 49 years residing in 30 communities that participate in the Rakai Community Cohort Study (RCCS) conducted by the Rakai Health Sciences Programme in Uganda. With funding from NIH and others, this programme promoted HIV testing, ART and voluntary medical male circumcision to study participants.
Every one or two years from April 1999 until September 2016, participants were tested for HIV and surveyed about their sexual behaviour, use of HIV treatment, and male circumcision status. The authors of the new paper analysed these survey data under the leadership of Dr M Kate Grabowski, an assistant professor at The Johns Hopkins University School of Medicine in Baltimore and an epidemiologist with the Rakai Health Sciences Programme.
The investigators found that the proportion of study participants living with HIV who reported taking ART climbed from zero in 2003 to 69% in 2016. The proportion of male study participants who were voluntarily circumcised grew from 15% in 1999 to 59% in 2016. While levels of condom use with casual partners and the proportion of people reporting multiple sexual partners remained largely unchanged, the proportion of adolescents ages 15 to 19 who reported never having sex rose from 30% in 1999 to 55% in 2016.
As an apparent consequence of these increases, particularly in ART use and voluntary male circumcision, the annual number of new HIV infections in the cohort fell from 1.17 per 100 person-years in 2009 to 0.66 per 100 person-years in 2016, a 42% decrease. Person-years are the sum of the number of years that each cohort member participated in the study. The researchers calculated the annual number of new HIV infections using data from nearly 18,000 of the almost 34,000 total participants.
In addition, the proportion of cohort members living with HIV whose treatment suppressed the virus increased from 42% in 2009 to 75% in 2016, showing the feasibility of meeting the goal of the UNAIDS 90-90-90 initiative to achieve 73% viral suppression.
"These findings are extremely encouraging and suggest that with sustained commitment to increase the number of people who use combination HIV prevention, it may be possible to achieve epidemic control and eventual elimination of HIV," said Dr David Serwadda, co-founder of the Rakai Health Science Programme and professor at Makerere University School of Public Health in Kampala, Uganda.
HIV incidence dropped the most – by 57% – among circumcised men, likely because both their own circumcision and ART taken by their female sexual partners living with HIV protected these men from the virus. HIV incidence declined by 54% among all men but by only 32% among all women. According to the investigators, this difference probably occurred because a greater percentage of women living with HIV than men living with HIV took ART, and because nearly two-thirds of men chose the extra preventive benefit of circumcision.
The researchers suggest addressing this gender imbalance by influencing more men living with HIV to take ART and by giving HIV-uninfected women HIV prevention tools that they can control unilaterally, such as pre-exposure prophylaxis (PrEP). The scientists anticipate that the RCCS will add PrEP to its combination HIV prevention package as the study continues.
"We expect that this multifaceted approach to HIV prevention will work as well in other populations as it has in rural Uganda," said Grabowski. "Our results make a strong case for further expanding ART and male circumcision for HIV prevention in Rakai District and beyond. Additional proven HIV prevention interventions, such as PrEP, should be added to the mix to reduce HIV infections in women and other high-risk groups."
The Rakai Health Sciences Programme is an independent research organisation whose collaborators include the Uganda Virus Research Institute of the Ministry of Health in Kampala; the NIAID division of intramural research-supported International Centre for Excellence in Research in Rakai; the US Centres for Disease Control and Prevention partnership with Uganda (CDC-Uganda); Makerere University and Johns Hopkins University.
Abstract
Background: 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.
Methods: 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.
Results: 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).
Conclusions: 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.
Authors
M Kate Grabowski, David M Serwadda, Ronald H Gray, Gertrude Nakigozi, Godfrey Kigozi, Joseph Kagaayi, Robert Ssekubugu, Fred Nalugoda, Justin Lessler, Thomas Lutalo, Ronald M Galiwango, Fred Makumbi, Xiangrong Kong, Donna Kabatesi, Stella T Alamo, Steven Wiersma, Nelson K Sewankambo, Aaron AR Tobian, Oliver Laeyendecker, Thomas C Quinn, Steven J Reynolds, Maria J Wawer, Larry W Chang
[link url="https://www.niaid.nih.gov/news-events/combination-hiv-prevention-reduces-new-infections-42-percent-ugandan-district"]NIH/National Institute of Allergy and Infectious Diseases material[/link]
[link url="http://www.nejm.org/doi/10.1056/NEJMoa1702150"]New England Journal of Medicine abstract[/link]