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The systematic review and meta-analysis also found ART roll-out did not improve the disparity of HIV incidence between adolescent girls and boys (aged 15 to 19), with teenage girls having significantly higher infection rates than teenage boys in all studies analysed. Incidence was found to be as high as 8% among adolescent girls in KwaZulu-Natal, South Africa while remaining less than 1% among adolescent boys in almost every setting.

The authors reviewed trends in HIV incidence among young people from the start of HIV treatment expansion, through to the launch of large prevention programmes targeting adolescent girls and young women. This includes the US President’s Emergency Plan for AIDS Relief’s (PEPFAR) DREAMS initiative, which began in 2014 with the goal of reducing HIV incidence among adolescent girls and young women by 40%.

The analysis examined studies reporting observed – rather than estimated – HIV incidence, based on serological samples collected between 2005 and 2015 among young people in Kenya, Malawi, Mozambique, South Africa, Swaziland, Tanzania, Uganda, Zambia, and Zimbabwe, nine of the ten DREAMS countries (no eligible studies from Lesotho were identified).

Decisions about where to implement programmes such as DREAMS have largely been based on data relating to HIV prevalence and modelled incidence estimates, which are more readily available than data on observed incidence. However, directly observed HIV incidence can be more useful for identifying both the timing of new infections and the populations at highest risk – and consequently the greatest windows of opportunity for prevention efforts.

The review found a limited number of studies used estimates based on directly observed incidence or observed incidence over time, disaggregated for age and sex. In total, 51 studies were included for analysis.

Since 2005, when ART roll-out began in east and southern Africa, data suggests HIV incidence among adolescent girls and young women declined in Rakai in Uganda, Manicaland in Zimbabwe and nationally across South Africa.

However, in settings with particularly high HIV prevalence among the general population and among young women belonging to other key populations, little evidence was found to suggest ART and other efforts had slowed transmission by 2016.

This includes KwaZulu-Natal, the highest-burden setting in South Africa, where HIV incidence rates among young women were found to match high-risk population groups (7.79 per 100 person-years among females aged 15–19 years, and 8.63 among females aged 20–24 years). Persistently high incidence rates were also found among young female sex workers in Zimbabwe (10.80 per 100 person-years), young female sex workers in South Africa (13.20 per 100 person-years), and adolescent girls and young women in Ugandan fishing communities (12.40 per 100 person-years in females aged 15–19 years and 4.70 in those aged 20–24 years).

The fact that the highest-risk young women are not appearing to benefit from the rollout of ART or other prevention efforts may be due, in part, to these women’s sexual partners being unaware of their HIV status or not being on treatment. ART coverage among HIV-positive men in their twenties and thirties – the age groups most likely to be sexually involved with adolescent girls and young women – is relatively low.

Disparities between young women and men’s HIV risk have also persisted since ART was rolled out. Despite wide geographical diversity between the studies analysed, HIV risk was higher among teenage girls (ages 15–19) than teenage boys in all studies, settings, and time-points. In pooled analyses, HIV risk was up to six times higher for adolescent girls in southern African and three times higher for adolescent girls in east Africa than their male peers. This difference was found to narrow when people hit their mid 20s, the point at which HIV incidence among men escalates.

In studies examining HIV incidence among the general population, women’s HIV risk was found to increase until their mid-twenties, when it typically peaks. In contrast, among young female sex workers, bar workers and guesthouse workers and young women attending STI clinics, risk was often higher among teenagers than those aged 20 or above. This may reflect the barriers high-risk adolescent girls face in accessing HIV testing and treatment services or negotiating condom use. It might also reflect the risk profiles of male partners.

Although the review shows recent declines in HIV incidence among adolescent girls and young women in some settings, it suggests the availability of ART and other interventions might be insufficient to reduce HIV infections among young women from higher-risk groups and in settings where HIV prevalence is particularly high. Neither does ART appear to be reducing the relative HIV risk for teenage girls.

This study adds further weight to the need for HIV prevention programmes to address the persistent gender and age inequalities that drive excessive HIV vulnerability among adolescent girls and high risk young women in order to tackle infections among the growing population of adolescents in sub-Saharan Africa. As the authors rightly point out, supporting men in their 20s and 30s through testing, prevention, and treatment cascades must be part of this solution.

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Long before I became president and director of Seattle’s Fred Hutchinson Cancer Research Center, I learned all-too-well the link between infectious disease and cancer.

As a medical student at the University of California, San Francisco during the 1980s, I witnessed the early days of the AIDS epidemic. Young men with HIV were dying in that city by the thousands of unusual opportunistic infections such as pneumocystis pneumonia and rare cancers such as Kaposi sarcoma.

I worked at San Francisco General Hospital on a medical team with Dr. Sue Desmond-Hellmann, who was also profoundly influenced by the suffering there; she went on to a successful career in oncology and infectious disease. Her star kept rising. At the biotechnology pioneer Genentech, she was responsible for the development of a plethora of novel cancer drugs including monoclonal antibodies such as trastuzumab, or Herceptin, for breast cancer and rituximab for B-cell malignancies. Then she returned to lead UCSF as chancellor, and today she is chief executive officer of our good neighbors in Seattle, the Bill & Melinda Gates Foundation.

While our paths have crossed frequently over the years, it was particularly meaningful recently when we met again — this time in, of all places, Kampala, Uganda.

For two pivotal years beginning in 1989, Sue had lived in that city studying HIV/AIDS and cancer at the Uganda Cancer Institute. Last month, she revisited Kampala, and together we walked through the UCI-Fred Hutch Cancer Centre, which is jointly operated by UCI and Fred Hutch’s Global Oncologyprogram. It is a world-class facility with a wonderful staff; and it is a place where the link between infectious diseases and cancer is witnessed daily.

Both of us found it humbling and inspiring to observe the great work being done by many young researchers working in challenging situations where so many cancer patients are also infected with HIV.

In sub-Saharan Africa, 33% of all cancers are caused by infectious agents; and HIV, which severely impairs a person’s immune system, can make that person even more prone to infection by other viruses that can lead to cancers. For example, about 85% of patients at UCI with Kaposi sarcoma — caused by a herpes virus that existed long before AIDS — are HIV-positive as well.

Kaposi sarcoma often presents as dark or purple lesions on the skin of individuals infected with HIV. Until effective antiviral drugs against HIV were developed, it was literally the face of AIDS in the United States. It still takes a toll in Uganda, despite a laudable program to provide these drugs to people there living with HIV.

While at UCI-Fred Hutch, Sue and I met a young woman, Margaret Sunday, who had arrived there with severe Kaposi sarcoma lesions covering her feet and legs. She had been under care for HIV and had been taking antiviral drugs. Sadly, despite this medical attention, her cancer had not been diagnosed early and had gone untreated.

It was immediately apparent that we are still missing something in the screening and treatment of HIV in sub-Saharan Africa. In the United States, HIV screeners also look for cancers. We look for other viral infections, like human papillomavirus, or HPV, that can lead to cervical cancer, understanding that the risk of cervical cancer in women with HIV — nearly all of whom also have HPV — is increased more than fivefold. For patients in the US with HIV, where treatment is widely available, the leading cause of death is no longer opportunistic infection as it was in the 1980s — rather, it is cancer. If we treat HIV but not the cancer, it is as if we are treating half the patient.

In Uganda, I believe we are making progress. The UCI-Fred Hutch Collaboration expands local capacity in scientific research, training and patient care, serving as a great model for addressing global health challenges.

Because of the challenges we face in treating cancer with chemotherapy and radiation therapy in a resource-limited environment, it is critically important that we reduce the cancer burden on patients in this region. We must strengthen all facets of cancer and HIV care — including screening, early diagnosis and all stages of treatment. We must strengthen the bonds between cancer prevention and infectious disease prevention. That is why UCI-Fred Hutch nurses who screen for HIV are also trained to tie the screening for cervical cancer to HIV testing and care.

I was gratified to see Sue reunite with some of the amazing people she worked with in Kampala in the 1980s. We saw staff equipped with advanced facilities and technologies that did not exist or were unthinkable three decades ago: a specimen-receiving lab, a histopathology lab for processing biopsies, a lab for genomic sequencing.

Sue and I also visited the medical records room containing paper records stacked to the ceiling dating back more than 50 years to the inception of the UCI. Remarkably, UCI-Fred Hutch staff pulled several charts from 1989–1990 with handwritten notes by Sue herself — very comprehensive notes I might add, with complete differential diagnoses included!

As vaccine programs are a central focus of the Gates Foundation, we further discussed our efforts to ensure broad vaccination with HPV vaccines. At the Hutch we are especially focused on HPV vaccines as they were developed with the help of insights from investigators like Dr. Denise Galloway, who holds the Paul Stephanus Memorial Endowed Chair. These were but a few of the truly memorable “full-circle” moments during our visit.

We will continue to work in close collaboration with our African colleagues to gain ground against both cancer and infectious diseases. We are all committed to using our understanding of the linkage between infectious disease and cancer to better treat — and prevent — them both.

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