CROI Opening Session: Guiding the Global Response

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This post is by Global Center Director Christine Lubinski, who is attending the Conference on Opportunistic Infections and Retroviruses (CROI) this week in San Francisco. This is her first post; check back regularly for her blogs throughout the conference.

The opening plenary of this leading HIV scientific conference—titled “Guiding the Global Response”—highlighted efforts to model the impact of ART as a prevention  and treatment tool to ultimately end the epidemic. CROI’s kick-off session also showcased issues related to couples and offered an assessment of current treatment strategies and scale-up in Africa.

In a talk entitled, “Put Your Money Where Your Model Is:  ART for Prevention and Treatment of HIV,” Brian  Williams, a modeler from South Africa asked why, despite the expenditure of $150 billion, the world has failed to control HIV transmission. He theorized that if an average of 7 people are infected by any one person, and if we reduce transmission 7 fold, we can eliminate HIV.  ART reduces viral load by 10,000 times, so if we start ART within one year of seroconversion and reduce Infectiousness by 70 percent, we can end the epidemic, Williams said.

While physicians and scientists are beginning to identify people early enough to save them from death, they are not intervening early enough to keep people from transmitting HIV to others.  He proposes a “test annually and treat immediately” strategy for low-prevalence settings, and a combination of test and treat and pre-exposure prophylaxis—or PREP—in high prevalence settings, like South Africa, which has a 17 percent HIV prevalence. Williams suggests that PREP would be appropriate for younger persons at high risk, while a test and treat strategy could be effectively deployed for older persons.  Benefits of this type of early intervention include a reduction in TB of about 60 percent.  Moreover, he noted that HIV-positive persons have a 2.5 times greater risk of mortality, compared to their HIV-negative counterparts, regardless of CD4 count or level of immunosupression.

Williams acknowledges that these strategies will require  a big initial capital outlay, but notes that we will ultimately save money in the long run.  If we don’t take measures to stem HIV transmission, we will continue to need huge fiscal resources to respond to the epidemic.  According to Williams, we can expect to spend $60 billion dollars, and the question is whether we will save millions of additional lives while incurring those costs.

He highlighted recent successful efforts at community-based testing in Kenya as an indication that test and treat could work. But an audience member responded that only about 30 percent of those identified as positive in this campaign were successfully linked to care and treatment.

Dr. Rebecca Bunnell, from the CDC, outlined the centrality of couples in the HIV epidemic in Africa and attributed the failure to significantly reduce HIV transmission rates in part to a failure to employ couple-based strategies.

She noted that the term “couple” describes many types of partnerships and that there are cultural, legal, and regional variations.  In a number of African countries in east and southern Africa, the majority of HIV-infected persons cohabiting are married.  Mutual knowledge of serostatus is low, and condom use is low. In east Africa, 40 to 50 percent of married HIV-infected persons have an uninfected spouse. There are an estimated 340,000 discordant couples in Kenya.  In Uganda, 74 percent of recent infections occurred in married couples. Studies have also shown that MSM who are part of a couple have a higher HIV risk than those who are not paired, as a result of more sex acts, more receptive sex, and less condom use.

Risk extends beyond the coupled, since concurrent external partnerships are also a major source of transmission. Reduction of external partnerships, testing, and condom use are essential, she said.

Bunnell argued that prevention and surveillance have been individually focused and couples have been ignored, despite their centrality to the epidemic in Africa. Moreover, prevention approaches have included the message that marriage is a safe haven from HIV infection. This has served to discourage persons in couples from being tested for HIV by creating the perception that they are at low risk and may well have increased HIV risk within discordant couples. 

Bunnell called for further scale up of couple-based approaches, including couples counseling and testing and prevention for positive programs aimed at couples.  She suggested that integration of these approaches within PMTCT programs, family planning services, male circumcision programs, as well as HIV treatment and TB treatment programs could enhance impact.

There is clear evidence that these strategies can be successfully implemented, she said, pointing to home-based testing programs in Uganda, couple testing programs within PMTCT programs in Rwanda, and partner testing programs for TB patients in Kenya.

For discordant couples, ART is critical long-term prevention, but treatment programs are becoming overwhelmed and access to ART is threatened by flat funding by donors.  Scale up of couple interventions could change the landscape of the epidemic.  For example, these strategies could conceivably prevent 36 to 60 percent of current transmission in Zambia. The neglect of couples has already had tragic implications, she said, translating into millions of deaths and millions of orphans.

Papa Salif Sow, a Senegalese infectious diseases physician, highlighted the “evolving realities of HIV treatment in resource-limited settings.”  He outlined a familiar litany of challenges, including the high early mortality of those initiating treatment with severe immunodeficiency and severe malnutrition; frequent HIV/TB co-infection; and difficulties with the use of the very toxic drug, d4t.  There are problematic interactions between HIV drugs and TB drugs, especially rifampycin, and rifabutin is usually not available as an alternative TB drug.  He noted that limited access to second-line ARV therapy and salvage therapy was a growing problem, as individuals on first-line therapy for longer periods of time begin the fail on those regimens.

Sow pointed out the urgent need for cheap point-of-care viral load tests to identify early viral failures and to limit the emergence of resistance.  To be effective and useful in resource-limited settings, these tests must be simple to use, independent of electronics, robust enough to withstand ambient temperatures, cost no more than $2, and have a shelf life longer than 12 months.

Another very serious problem associated with ART scale up has been the more than 20 percent of patients lost to follow up after starting ART.  According to Sow, there are many reasons for this, including the challenges and high costs associated with transportation to clinic settings and the actual cost of ART in some countries. He noted, for example, that in Tanzania, patients are expected to pick up 50 percent of the ART costs.

He concluded by underscoring the need for cheap viral load monitoring, greater availability of cheaper second-line regimens, better tools to identify and manage co-infection with TB and hepatitis B, and additional resources to respond to the demand for HIV testing and subsequent linkage to HIV care and treatment.

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