HIV Treatment Scale-Up in Uganda, 2004–2022: Infections and Deaths Averted

In brief. The U.S. President's Emergency Plan for AIDS Relief (PEPFAR) was announced on January 28, 2003 — the largest commitment by any nation to fight a single disease. In April 2004 a 34-year-old man in Uganda became the first person in the world to receive PEPFAR-supported antiretroviral therapy (ART). By September 2022 more than 1.3 million people with HIV in Uganda were receiving it. Over 2004–2022, the scale-up helped avert nearly 500,000 HIV infections, more than 230,000 of them in infants exposed to HIV, and about 600,000 HIV-related deaths.

Effective ART reduces illness and death among people with HIV. It also prevents transmission from mother to child and — once the viral load is suppressed to undetectable levels (fewer than 200 copies per mL) — sexual transmission.

HIV in Uganda

• Early 1980s — the first local AIDS cases are recognised.
• October 1986 — the Ministry of Health sets up the Uganda AIDS Control Program (ACP), at first focused on prevention and palliative care, since there was no treatment.
• Early 1990s — HIV prevalence begins to fall, linked to less casual sex and more protective behaviour such as condom use.
• 2002 — the ACP starts a national programme to prevent mother-to-child transmission, after the HIVNET 012 trial in Uganda showed nevirapine could prevent it.
• April 2004 — Uganda is the first country to provide PEPFAR-supported ART, at first for people with advanced disease (for example, a CD4 count below 200 cells/μL).
• 2012 — "Option B+" opens ART to all pregnant and breastfeeding women with HIV.
• 2015 — "Treat All" opens it to everyone with HIV, however severe the disease.
• 2018 — dolutegravir-based regimens, such as tenofovir, lamivudine and dolutegravir (TLD), are introduced to make treatment more effective.
• From March 2020 — COVID-19 disrupts services; movement restrictions keep patients from appointments and refills.

Beyond clinical care and supplies, PEPFAR has helped build Uganda's health system: training and supporting health workers, leadership and governance, financing, information, laboratory and supply-chain systems, and folding HIV care into general health services. It works alongside UNAIDS and the Global Fund to Fight AIDS, Tuberculosis and Malaria in support of the Government of Uganda. In 2021 UNAIDS estimated 1.4 million people with HIV in Uganda (range 1.3–1.6 million), with about 54,000 new infections a year (43,000–69,000).

How the analysis was done

PEPFAR's monitoring and archival programme data were analysed by fiscal year (October–September); breakdowns by sex and by age — adults 15 and over, children under 15 — exist from 2005. Someone counted as on ART if their last appointment at a PEPFAR-supported site was within 90 days, a window cut to 28 days in October 2018.

• Proxy mother-to-child transmission rate (2010–2022): HIV-positive results among tested infants exposed to HIV during pregnancy or breastfeeding (up to 18 months after birth).
• Viral load suppression (2016–2022): fewer than 1,000 copies per mL, among those tested.
• Infections and deaths averted: the 2021 UNAIDS Spectrum AIDS Impact Model and Goals models, run by mid-year (July–June), compared with a scenario in which treatment stayed at 2003 levels — when about 2% of people with HIV were on ART — and the prevention programme reached no more women than in 2003.

Results

People on treatment. From September 30, 2004 to September 30, 2022, the number on PEPFAR-supported ART rose from 26,365 to 1,313,952, an increase of 4,884%.

Mother-to-child transmission fell from 6.4% in 2010 (2,327 positive of 36,119 infants tested) to 1.5% in 2022 (1,060 of 71,265) — a 77% drop.

Viral load. Tests rose 130%, from 526,936 in 2016 to 1,213,707 in 2022, and the suppression rate rose from 91% (479,915) to 94% (1,145,839). In September 2022 suppression was higher among adults (95%, 1,116,888 of 1,179,551) than children (85%, 28,951 of 34,156), and slightly higher among women (95%, 757,248 of 797,462) than men (93%, 388,591 of 416,245).

Averted. Over 2004–2022 an estimated 491,345 infections were averted, 231,833 of them among infants exposed to HIV — a median of 21,408 a year, from 913 in 2004 to 57,171 in 2022. An estimated 586,074 deaths were averted, from 1,138 in 2004 to 48,348 in 2022 (median 32,179 a year).

The first patient

In February 2004 a 34-year-old Ugandan man was diagnosed with HIV; a CD4 test in March found 1 cell/μL. In April he became the first person in the world to start PEPFAR-supported ART, on stavudine, lamivudine and nevirapine. He took tuberculosis preventive therapy from May to November 2020 and moved to TLD in January 2021; since March 2021 he has had no diagnosis of active tuberculosis or an HIV-related opportunistic infection. As of September 2022 he collects four months of medicine at a time, and his latest viral load test, in March 2022, showed suppression, which qualified him for a fast-track refill programme. Twenty years after PEPFAR was announced, he is 53 and still on treatment.

What it means

During 2020–2022 services adapted to the pandemic, adding 98,012 people on treatment and raising suppression rates. Suppression improved notably after dolutegravir arrived. Treatment is also prevention, as the falling transmission to infants shows.

Gaps remain. People with HIV who are not on treatment, or not suppressed, face poor outcomes and can pass on the virus. Men's suppression rates are slightly below women's, and children's remain under 90%, so children need individually optimised treatment. Infants are still born with HIV or acquire it in their first months and will need lifelong treatment. The 2020–2021 Uganda Population-based HIV Impact Assessment, a national survey of adults, confirmed the differences in suppression and found that 80.9% of people with HIV knew their status and 96.1% of those were on ART — so linkage to care is strong, but more people need to be found and tested.

The next step is to find everyone with HIV and link them quickly to effective treatment. PEPFAR says it will keep working with the Government of Uganda, civil society and other partners toward the UNAIDS goal of ending the AIDS epidemic by 2030 and keeping the gains made.

Limitations

• Definitions and reporting systems changed over time, which may have affected data quality despite ongoing quality checks.
• People can use any site, wherever they live, so some may have been counted twice — which also made it impossible to measure treatment coverage directly.
• The transmission rate may be too low, because untested infants were not counted.
• The models credit averted infections and deaths to ART alone, though other services such as voluntary medical male circumcision and other factors may have contributed; averted infections may also be underestimated.
• PEPFAR's share cannot be separated from that of the Government of Uganda, UNAIDS, the Global Fund and others, whose investments worked together.

Sources

• Dirlikov E, Kamoga J, Alamo Talisuna S, et al. Scale-Up of HIV Antiretroviral Therapy and Estimation of Averted Infections and HIV-Related Deaths — Uganda, 2004–2022. MMWR Morbidity and Mortality Weekly Report, CDC; with PEPFAR Uganda and the Uganda Ministry of Health's AIDS Control Program.