Scale-Up of HIV Antiretroviral Therapy and Estimation …

On January 28, 2003, the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR), the largest commitment by any nation to address a single disease in history, was announced.* In April 2004, the first person in the world to receive PEPFAR-supported antiretroviral therapy (ART) was a man aged 34 years in Uganda. Effective ART reduces morbidity and mortality among persons with HIV infection (1) and prevents both mother-to-child transmission (MTCT) (2) and sexual transmission once viral load is suppressed to undetectable levels (<200 viral copies/mL) (3). By September 2022, more than 1.3 million persons with HIV infection in Uganda were receiving PEPFAR-supported ART, an increase of approximately 5,000% from September 2004. As indicators of the ART program’s effectiveness, a proxy MTCT rate decreased 77%, from 6.4% in 2010 to 1.5% in 2022, and the viral load suppression rate (<1,000 viral copies/mL) increased 3%, from 91% in 2016 to 94% in September 2022. During 2004–2022, ART scale-up helped avert nearly 500,000 HIV infections, including more than 230,000 infections among HIV-exposed infants, and approximately 600,000 HIV-related deaths. Going forward, efforts will focus on identifying all persons with HIV infection and rapidly linking them to effective ART. PEPFAR remains committed to continued strong partnership with the Government of Uganda, civil society, and other development partners toward sustainable solutions aligned with the Joint United Nations Programme on HIV/AIDS (UNAIDS) fast-track strategy to ending the global AIDS epidemic by 2030^† and safeguarding impact achieved in the long term.

Local cases of AIDS were first recognized in Uganda in the early 1980s (4). In October 1986, the Uganda AIDS Control Program (ACP) was established within the Ministry of Health, initially focused on HIV prevention and palliative care, because of the lack of treatment options at the time (5). HIV prevalence started to decline in the early 1990s, linked to reductions in casual sex and increased protective sexual behavior (e.g., condom use) (6,7). In 2002, ACP established a national HIV MTCT prevention program (8), after the HIVNET 012 trial, which was conducted in Uganda and found that nevirapine could prevent MTCT (9).

In April 2004, Uganda was the first country in the world to provide PEPFAR-supported ART. Since then, ART eligibility criteria have expanded from an initial focus on patients with advanced disease (e.g., CD4 count <200 cells/μL). In 2012, “Option B+” expanded ART eligibility to all pregnant and breastfeeding women with HIV infection (8), and in 2015, “Treat All” expanded ART eligibility to all persons with HIV infection regardless of disease severity or other criteria.^§ In 2018, Uganda introduced dolutegravir-based regimens (e.g., tenofovir, lamivudine, and dolutegravir [TLD]), with the goal of improving ART effectiveness.^¶ Since March 2020, the COVID-19 pandemic has affected medical services, including the HIV program; for example, movement restrictions limited patients’ ability to attend clinics for appointments and ART refills (10). In addition to clinical services and commodity procurement, PEPFAR has also supported health system–strengthening activities, including workforce capacity building and support to health workers; leadership and governance capacity building; development of financing, information, laboratory, and supply chain systems; and integration of HIV services into the general health system.** PEPFAR Uganda has worked in collaboration with other stakeholders, including UNAIDS and the Global Fund to Fight AIDS, Tuberculosis, and Malaria, to ensure optimized resource utilization in support of the Government of Uganda. By 2021, UNAIDS estimated that there were 1.4 million (range = 1.3–1.6 million) persons with HIV infection in Uganda, with an estimated 54,000 (range = 43,000–69,000) new infections occurring annually.^††

To describe the scale-up of PEPFAR-supported ART, PEPFAR Monitoring, Evaluation, and Reporting and archival programmatic data^§§ were analyzed by fiscal year (October–September); data permitting comparison by sex and age group (adults [persons aged ≥15 years] and children and adolescents [persons aged <15 years]) have been available since 2005. Before October 2018, persons with HIV infection on ART were defined as clients at a PEPFAR-supported site if ≤90 days had elapsed since their last appointment; in October 2018, this definition changed to ≤28 days since the last appointment. The proxy MTCT rate was calculated as the number of HIV-exposed infants during pregnancy or the breastfeeding period (i.e., 18 months postpartum) who had a positive HIV test result among those who received testing (data available for 2010–2022). Viral load suppression was defined as <1,000 HIV viral copies/mL, and the suppression rate was calculated as the number of persons with HIV infection with viral load suppression among those who had received a viral load test (data available for 2016–2022). The 2021 UNAIDS Spectrum AIDS Impact Model (AIM) and Goals ASM models were used to estimate the number of infections averted, including among HIV-exposed infants, and HIV-related deaths averted by mid-year (July–June). Both models use national program statistics, survey and surveillance data, and study-derived epidemiologic parameters to calibrate structured models of HIV transmission and produce indicators such as incidence and mortality.^¶¶ To estimate the number of infections and deaths averted in the absence of PEPFAR, the number of persons with HIV infection on ART were interpolated using program data from 2003 when an estimated 2% of persons with HIV infection were on ART, with 2% of the program numbers for 2021; the number of women reached by the MTCT prevention program was held constant from 2003 levels. Data from the electronic medical records for the first person to receive PEPFAR-supported ART were abstracted from the clinic where he first received ART and from the clinic where he last received ART. This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy.***

During September 30, 2004–September 30, 2022, the number of persons with HIV infection on PEPFAR-supported ART increased 4,884%, from 26,365 to 1,313,952 (Figure 1). During September 30, 2005–September 30, 2022, the number of adults with HIV infection receiving PEPFAR-supported ART increased 2,687%, from 45,061 to 1,255,983, and the number of children with HIV infection on PEPFAR-supported ART increased 1,167%, from 4,577 to 57,969. The number of women and men with HIV infection on PEPFAR-supported ART increased 3,723%, from 28,836 to 853,103, and 2,115%, from 20,802 to 460,849, respectively.

The proxy MTCT rate declined from 6.4% (2,327 HIV-positive infants exposed during pregnancy or 18 months postpartum among 36,119 tested) in 2010 to 1.5% (1,060 of 71,265) in 2022 (Figure 2). During 2016–2022, the number of viral load tests conducted increased 130%, from 526,936 to 1,213,707, and the viral load suppression rate increased from 91% (479,915 of 526,936) to 94% (1,145,839 of 1,213,707) (Figure 2). In September 2022, viral load suppression rates were higher among adults (95% [1,116,888 of 1,179,551]) than among children (85% [28,951 of 34,156]), and slightly higher among women (95% [757,248 of 797,462]) than among men (93% [388,591 of 416,245]).

During 2004–2022, an estimated 491,345 HIV infections were averted, including 231,833 among HIV-exposed infants. Annually, a median of 21,408 HIV infections were averted, ranging from 913 in 2004 to 57,171 in 2022 (Figure 3). During this period, an estimated 586,074 deaths were averted, ranging from 1,138 in 2004 to 48,348 deaths in 2022 (annual median = 32,179).