Models: Tools to Improve Decision Making about HIV

Via AIDS.gov, by Ronald Valdiserri, M.D., M.P.H.

For those of us who work in the HIV/AIDS field, the month of July was dominated by exciting HIV prevention news coming out of the International AIDS Society meeting in Rome. Results from the HPTN 052 study showed that early, compared to delayed, antiretroviral treatment resulted in a 96% reduction in HIV transmission to uninfected partners. The TDF2 study conducted by CDC in partnership with the Botswana Ministry of Health, found that a once-daily pill containing two anti-HIV drugs reduced the risk of acquiring HIV infection by about 63% in a study population of healthy, heterosexual men and women. These and other study findings continue to add weight to the notion that HIV treatment is prevention. All of us are encouraged when we think about how these findings could be translated into real world settings in a way that would bring us closer to achieving the goals of the National HIV/AIDS Strategy.

Without minimizing the tremendous enthusiasm that rightly attends the prevention breakthroughs that were presented in Rome, I would like to talk about another scientific discussion that took place in July. As it turns out, this meeting was also held in a world capital, although to a much smaller audience. And while the results of this two-day meeting didn’t garner media attention the same way as the Rome meeting did, the topics under discussion were no less consequential.  In mid-July, I was very fortunate to attend a two-day workshop on “Modeling and Evidence-Based Decision Making” sponsored by amfAR, the Foundation for AIDS Research and cosponsored by the Kaiser Family Foundation, the National Alliance of State and Territorial AIDS Directors, and the Urban Coalition for HIV/AIDS Prevention Services. Meeting participants included colleagues from state and local departments of health, academia, federal government, and professional and community-based organizations.

Colleagues from Los Angeles, San Francisco, Maryland, and New York City shared with us their experiences with using various models to assist in making decisions about “optimizing” HIV prevention investments. Using different approaches, each of these health departments was trying to answer the same question, “What combination of prevention services and activities will result in the greatest reduction of the number of new HIV infections?”

At the onset of the meeting, we were reminded that modeling is used in other areas of health and public policy decision-making, especially when leaders are trying to combine diverse information from a variety of sources in order to make sound decisions at a population level.  However, even the biggest fans of modeling reminded us that a model is not a “crystal ball” nor is it infallible.  Instead, what models do is provide a tool to help us make better decisions about complex realities. Good models should always be clear about the inputs and assumptions that were used to generate the results. And perhaps most importantly, they should be used to guide rather than to conclude any discussions about how best to allocate resources.

Read the rest here.

[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

Retention of pre-ART patients poor in sub-Saharan Africa

Via AIDSMap, by Lesley Odendal.

 More than two-thirds of people who tested positive for HIV but weren't yet eligible for treatment when diagnosed were lost from care, according to a systematic review of pre-antiretroviral (pre-ART) care in sub-Saharan Africa, published this month in PLoS Medicine.

Studies included in the review report a substantial loss of patients at every step of care, starting with patients who do not return for their initial CD4 count results and ending with those who do not initiate ARVs despite eligibility, according to Sydney Rosen and Matthew Fox of the Center for Global Health and Development at Boston University, who conducted the review.

The study was conducted in order to evaluate the extent to which patients diagnosed with HIV are being lost before starting treatment.

28 studies which reported on the proportion of adult patients retained between any two points between testing positive for HIV and initiating ART in sub-Saharan African HIV/AIDS care programs were included. Results were categorised into stages of pre-ART care with ranges  reported for the proportions of patients retained in each stage.

Stages were categorised as follows:

• Stage 1: from HIV testing to receipt of CD4 count results or clinical staging
• Stage 2: from receipt of CD4 count results or clinical staging to ARV eligibility
• Stage 3: from ARV eligibility to ARV initiation

The review found that the median proportion of patients retained in Stage 1 was 59% (ranging from 35%–88%); Stage 2, 46% (31%–95%); and Stage 3, 68% (14%–84%).  'Loss to care' was defined as failing to reach the next step in the care sequence for any reason (death or discontinuation), but each study’s own criteria for determining which patients died or discontinued care were also included.

There are several key reasons for the poor retention of pre-ART care patients. As most patients are asymptomatic during the pre-ART period, they may not perceive themselves as requiring medical care. Patients may also not come to the clinic for monitoring and may choose to ‘‘wait and see what happens’’  if they "lack resources for transport, risk losing employment by taking time off work, or fear being recognised as a client of an HIV clinic," write the authors. Those presenting with a low CD4 count are likely to have died before reaching stage 3. Patient mobility may also be a factor contributing to low retention rates.

 Read the rest here.

[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

Retention in HIV Care between Testing and Treatment in Sub-Saharan Africa: A Systematic Review

Published in the July 2011 Issue of PLoS Medicine.

 

Background

Improving the outcomes of HIV/AIDS treatment programs in resource-limited settings requires successful linkage of patients testing positive for HIV to pre–antiretroviral therapy (ART) care and retention in pre-ART care until ART initiation. We conducted a systematic review of pre-ART retention in care in Africa.

 

Methods and Findings

We searched PubMed, ISI Web of Knowledge, conference abstracts, and reference lists for reports on the proportion of adult patients retained between any two points between testing positive for HIV and initiating ART in sub-Saharan African HIV/AIDS care programs. Results were categorized as Stage 1 (from HIV testing to receipt of CD4 count results or clinical staging), Stage 2 (from staging to ART eligibility), or Stage 3 (from ART eligibility to ART initiation). Medians (ranges) were reported for the proportions of patients retained in each stage. We identified 28 eligible studies. The median proportion retained in Stage 1 was 59% (35%–88%); Stage 2, 46% (31%–95%); and Stage 3, 68% (14%–84%). Most studies reported on only one stage; none followed a cohort of patients through all three stages. Enrollment criteria, terminology, end points, follow-up, and outcomes varied widely and were often poorly defined, making aggregation of results difficult. Synthesis of findings from multiple studies suggests that fewer than one-third of patients testing positive for HIV and not yet eligible for ART when diagnosed are retained continuously in care, though this estimate should be regarded with caution because of review limitations.

 

Conclusions

Studies of retention in pre-ART care report substantial loss of patients at every step, starting with patients who do not return for their initial CD4 count results and ending with those who do not initiate ART despite eligibility. Better health information systems that allow patients to be tracked between service delivery points are needed to properly evaluate pre-ART loss to care, and researchers should attempt to standardize the terminology, definitions, and time periods reported.

[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

IN CONVERSATION WITH DR. SONALI KOCHHAR: PrEP in India

Dr. Sonali Kochhar, medical director India of OneWorld Health and one of the two Indian women chosen for the prestigious 2011 Yale World Fellows leadership initiative, provides a thoughtful discussion on PrEP within the Indian context.

MP: Could you please briefly introduce yourself, and tell us how you got involved in the field of HIV prevention?

SK: I was the Medical Director, India for the International AIDS Vaccine Initiative for seven years and was involved in the preparation and conduct of the first ever AIDS vaccine trials conducted in India.

I got involved in the field of HIV prevention because early on in my medical training, I saw firsthand how diseases like HIV not only severely impacted the person infected but also their whole families. The severe stigma and discrimination associated with the disease in developing countries like India only worsens the issues. Seeing women being disowned by their families and children thrown out of schools and shunned by society convinced me that it is imperative that safe, effective and accessible preventive options are found at the earliest to prevent these tragedies. History has shown that vaccines are often the most powerful and cost-effective disease prevention tools available. It is hoped that a preventive AIDS vaccine will stem the global HIV pandemic.   

MP: What are your thoughts on PrEP, particularly within the Indian context?

SK: There is mounting evidence that pre-exposure prophylaxis might prove to be an important new prevention approach. The results of from the iPrEx trial were promising in showing that in MSM and transgendered women who have sex with men, daily TDF/FTC (tenofovir disoproxyl fumarate plus emtricitabine, Truvada) reduced the risk of HIV by 44 percent.

If proven safe and effective in all populations[1], PrEP could help address the urgent need for a female-controlled prevention method for women who are often unable, because of cultural and financial barriers, to negotiate condom use.

It could be used by men and women at risk due to sexual or drug-using behaviors, when combined with prevention measures like reducing the number of sexual partners, HIV counseling and testing, condom use, use of sterile syringes etc.

  

MP: What are the particular pros and cons, challenges, or issues of rolling out PrEP here? Do you think it should be made accessible to everyone?

SK: There are numerous questions about the implementation of PrEP outside of the research setting especially in the context of countries like India with problems like the lack of a strong evidence base on which to formulate decision making, an unregulated health sector and a highly vulnerable population often severely disadvantaged in terms of income, education, power structures and gender.

These include whether the intermittent use of the drugs will be effective, how the cost will be borne and how would the health and safety of PrEP users be monitored. The impact of PrEP may be strongly diminished or even reversed by behavioral disinhibition (increased risky sexual behavior because people may feel protected against HIV infection), especially in scenarios with low coverage and low effectiveness. PrEP would need to be used with other preventive modalities but it is not certain how this can best be done.

Large-scale PrEP use might encounter problems such as poor adherence and resistance. One of the problems of intermittent use, besides reduced effectivity, is possible emergence of resistant viruses.

If clinical trials demonstrate efficacy of PrEP, as many expect, the demand for its provision may increase rapidly. Indian Policymakers, Program Planners and Public Health Workers will need to prepare for this. This will include the development of national testing and assessment protocols, behavioral interventions, ensuring uninterrupted supply of PrEP and monitoring the population-level impacts of PrEP use.

To support the use of PrEP as a population-level prevention strategy, I feel that the following issues need to be resolved:

1) PrEP drugs – The challenges encountered in countries like India would include ensuring financing for an uninterrupted supply of drugs, training and retaining health workers; establishing and maintaining clinical, laboratory, and public health infrastructure; overcoming barriers to accessing care such as stigma, lack of awareness, and geographical distance; implementing appropriate monitoring and evaluation systems; sustaining patient adherence; and managing drug-related toxicity and resistant infections. Guidelines for PrEP eligibility, optimal PrEP dosing, necessary adherence, route of administration and channels for PrEP prescription and monitoring would need to be developed.

2) Safety screening – To address the risk of new HIV infection, including the acquisition of drug-resistant HIV and the development of secondary resistance in PrEP users, repeated and frequent HIV testing would be required. This will require  laboratory costs and infrastructure expansion. PrEP may only be cost effective for individuals at high risk for HIV. Side effects of PrEP like loss of bone density or renal impairments, will require ongoing clinical and laboratory monitoring.

3) Integration of PrEP as part of comprehensive care – As PrEP implementation requires clinical assessment, prescription, routine testing, and long-term monitoring of PrEP users, it will require a frequent and stable interface between PrEP users and clinical providers in an ideal scenario.

MP: Looking at the big picture, who do you think would benefit most from PrEP?

SK: Keeping in mind the above mentioned challenges, initial efforts might target members of known high-risk groups, such as sex workers, high-risk men who have sex with men, HIV negative individuals in serodiscordant sexual partnerships, and high-risk injection drug users.

MP: Is there any experience that stands out to you from your time on the field, which had an impact on you or that you can’t forget?

SK: Working with vulnerable populations like transgender individuals and men who have sex with men (MSM) was really an eye opener. These are people who often have nothing to their name (often not even a roof over their head), are disowned by society and their families and are completely discriminated and stigmatized against.[2] Yet a number of them were keen to help spread awareness about HIV/AIDS, prevention options and vaccines so that others may benefit from the information and not get infected with HIV. This degree of humanity is truly remarkable.

Dr. Sonali Kochhar is currently the medical director for India at OneWorld Health, where she leads efforts to develop safe, affordable, and accessible drugs and vaccines for diseases prevalent in the developing world.

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[1] Since the time of this interview – two additional studies – the Partners PrEP study and the CDC Bostswana study have shown that PrEP works in heterosexual individuals.

[2] To know more about HIV/AIDS in LGBT communities,  read HIV Prevention and LGBT Communities: Syndemics, Resilience, and Real Change.

[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

HIV researcher plans new PrEP study

Via Now Chelsea, by Sam Spokony.

Few methods of HIV prevention have been as promising, or as controversial, as pre-exposure prophylaxis (PrEP). After a history of underground practice and off-label prescriptions, the approach has recently begun to receive serious attention from researchers, policy makers and health care advocates.

An outgrowth of post-exposure prophylaxis (or PEP, a short-term antiretroviral treatment that has been used since the early 90s to decrease the likelihood of HIV infection after exposure to the virus, either occupationally or through sex), PrEP is a similar antiretroviral that can be taken by HIV-negative individuals in order to help prevent them from seroconverting (being infected).

The results of a Phase III clinical study known as iPrEx were published in the New England Journal of Medicine on November 23, 2010. The study showed that, in a group of 2,499 gay men, PrEP — in the form of a combination of drugs under the brand name Truvada — was 44 percent effective in preventing HIV seroconversion.

Under the guidance of Dr. Roy Gulick (director of the Weill Cornell Medical College HIV Clinical Trials Unit), a new experiment called the NEXT (Novel Explorations of Therapeutics) PrEP Study will begin this fall. It will include 400 at-risk, HIV-negative gay men, and will take place over 48 weeks at 12 sites across the U.S. and Puerto Rico.

The NEXT PrEP Study will differ from iPrEx in that its primary experimental group will receive a daily regimen of the drug maraviroc (brand name Selzentry). The control group will receive Truvada, and two other experimental groups will receive combinations of maraviroc and either tenofovir or FTC (the two individual drugs that make up Truvada). A major goal of the study, along with testing the HIV-prevention efficacy of maraviroc, will be to gauge the side effects of the drug on participants.

“The longest any HIV-negative person has taken PrEP in a clinical study is 12 weeks,” Gulick told Chelsea Now in a July 23 phone interview. [This is inaccurate. The participants in iPrEx, for instance, were followed about 14 months - MP] “Now, since this is a drug we’re giving to healthy people, the next step is exploring further to prove that it is both safe and tolerable for them.”

Read the rest here.

[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]