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Oral Pre-exposure Prophylaxis (PrEP) for HIV

This is an interim intervention report. We have spent limited time to form an initial view of this program, and at this point, our views are preliminary. We may consider undertaking additional work on this program in the future.

Summary

  • What is the program? Oral pre-exposure prophylaxis (PrEP) is the use of antiretroviral drugs by HIV-negative individuals to prevent HIV acquisition.
  • What is its evidence of effectiveness? We have reviewed two meta-analyses of randomized controlled trials of oral PrEP (including a Cochrane review) that conclude that PrEP significantly reduces the risk of acquiring HIV among individuals in high-risk groups. We have not yet seen evidence that large-scale charity-supported PrEP programs in sub-Saharan Africa have successfully increased rates of PrEP coverage.
  • How cost-effective is it? We are very uncertain about the costs of oral PrEP programs. Our very rough cost-effectiveness analysis suggests that oral PrEP programs are unlikely to be more cost-effective at preventing new HIV infections than voluntary medical male circumcision (VMMC).
  • Does it have room for more funding? We have not yet attempted to investigate this question.
  • Bottom line: We do not currently plan to prioritize additional work on this program, but may revisit it in the future.


Published: August 2017

What is the problem?

The annual incidence of new HIV infections remains high, especially in sub-Saharan Africa. The Joint United Nations Programme on HIV/AIDS (UNAIDS) estimates that there were 2.1 million new HIV infections in 2015, and that 1.4 million of these new infections occurred in sub-Saharan Africa.1

What is the program?

Oral pre-exposure prophylaxis (PrEP) is the use of antiretroviral drugs (tenofovir disoproxil fumarate (TDF) alone or in combination with emtricitabine (FTC)) by people who are not infected with HIV.2 PrEP is intended to prevent new HIV infections.3 In 2014, the World Health Organization (WHO) recommended that healthcare providers offer PrEP to men who have sex with men, and in 2015 WHO expanded its recommendation to cover anyone with a substantial risk of acquiring HIV (population groups with an HIV incidence of at least 3 per 100 person-years are defined as having substantial risk).4

Ongoing and planned PrEP pilot programs in sub-Saharan Africa have targeted members of serodiscordant couples (HIV-negative men and women whose partners are HIV-positive), men who have sex with men, sex workers, and adolescent girls and young women.5 (To date, we have focused our review of PrEP on sub-Saharan Africa.6)

In addition to the provision of antiretroviral drugs, implementing PrEP programs may also involve HIV testing, marketing or educational programs aimed at potential recipients, training for health care providers, regular renal function and hepatitis B infection testing, and support programs to encourage adherence to treatment.7

Does the program have strong evidence of effectiveness?

In short:

  • We have reviewed a Cochrane review (Okwundu et al. 2012) of six RCTs of oral PrEP and a more recent meta-analysis (Fonner et al. 2016) of ten RCTs of oral PrEP. Both reviews concluded that oral PrEP significantly reduces the risk of acquiring HIV among high-risk individuals. We would guess that we would agree with the conclusions of these two reviews after further analysis, but we have not yet fully analyzed the evidence base ourselves.
  • We have not yet seen evidence that large-scale charity-supported PrEP programs in developing countries have successfully increased rates of PrEP coverage among high-risk populations or reduced rates of new HIV infections.

The Cochrane review summarizes the results of six randomized controlled trials. It states:8

We identified 12 randomised controlled trials that meet the criteria for the review. Six were ongoing trials, four had been completed and two had been terminated early. Six studies with a total of 9849 participants provided data for this review. The trials evaluated the following: daily oral tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) versus placebo; TDF versus placebo and daily TDF-FTC versus intermittent TDF-FTC. One of the trials had three study arms: TDF, TDF-FTC and placebo arm. The studies were carried out amongst different risk groups, including HIV-uninfected men who have sex with men, serodiscordant couples and other high risk men and women. Overall results from the four trials that compared TDF-FTC versus placebo showed a reduction in the risk of acquiring HIV infection (RR 0.49; 95% CI 0.28 to 0.85; 8918 participants). Similarly, the overall results of the studies that compared TDF only versus placebo showed a significant reduction in the risk of acquiring HIV infection (RR 0.33; 95% CI 0.20 to 0.55, 4027 participants). There were no significant differences in the risk of adverse events across all the studies that reported on adverse events. Also, adherence and sexual behaviours were similar in both the intervention and control groups.

Trials included in the Cochrane review took place in several countries in sub-Saharan Africa and South America, as well as the United States and Thailand.9

Fonner et al. 2016 includes a meta-analysis of 10 RCTs of oral PrEP: the six randomized controlled trials included in the 2012 Cochrane review along with four additional placebo-controlled RCTs.10 In a combined analysis of RCTs of both types of oral PrEP drugs (TDF and TDF-FTC), Fonner et al. 2016 finds similar results overall to the Cochrane review: a risk ratio (RR) of 0.49 (95% CI 0.33-0.73, 17,423 participants), suggesting that PrEP may reduce the risk of acquiring HIV in high-risk individuals by 51%.11

Limitations to the evidence base include the following:

  • Since the total number of new HIV infections in either treatment or control groups in the meta-analysis is relatively low, the 2012 Cochrane review finds the overall quality of the evidence for the effectiveness of PrEP to be moderate.12 We do not know whether including the additional RCTs included in Fonner et al. 2016 would cause the authors of the Cochrane review to upgrade their assessment of the quality of the evidence.
  • Both the 2012 Cochrane review and Fonner et al. 2016 note that there is significant heterogeneity in the results and suggest that the heterogeneity may be caused by differing levels of adherence to the treatment regimen across the trials.13 We have not investigated this explanation or other possible explanations for heterogeneity.

We searched for, but did not find, evidence that charity-supported PrEP programs in sub-Saharan Africa have successfully increased PrEP coverage among high-risk populations at a large scale. Our impression is that this is because there have not yet been large-scale PrEP programs in sub-Saharan Africa.14

The World Health Organization notes several potential negative/offsetting impacts of PrEP, including the development of drug resistance, declines in bone mineral density, and declines in renal function; we have not investigated these or other potential negative impacts in depth.15

How cost-effective is the program?

Our preliminary conclusion is that oral PrEP programs are unlikely to be more cost-effective at preventing new HIV infections than voluntary medical male circumcision (VMMC).16

One particularly important point of uncertainty is on the costs of oral PrEP programs. To estimate the total cost per person of oral PrEP programs in sub-Saharan Africa we considered the following information:

  • Generic TDF costs around $43 per person per year, and generic TDF-FTC costs around $78 per person per year.17
  • A systematic review of oral PrEP cost-effectiveness modeling studies (Gomez et al. 2013) includes three estimates of the full costs of scaling up oral PrEP programs in southern Africa, which ranged from $150 to $250 per person per year.18
  • The Bill and Melinda Gates Foundation made a four-year grant focused on PrEP scale-up in Kenya for $22.3 million with the aim of reaching 20,000 people. This implies a cost of around $279 per person per year.19

Our rough cost-effectiveness analysis, based primarily on the planned large-scale program in Kenya mentioned above, is here.20

Note that our cost-effectiveness analyses are simplified models that do not take into account a number of factors. For example, our current model does not take any potential harms from side effects of PrEP into account.

There are limitations to this kind of cost-effectiveness analysis, and we believe that cost-effectiveness estimates such as these should not be taken literally, due to the significant uncertainty around them. We provide these estimates (a) for comparative purposes and (b) because working on them helps us ensure that we are thinking through as many of the relevant issues as possible.

Does the program appear to have room for more funding?

We note that implementation of large-scale oral PrEP programs outside of the United States has been limited to date, but we have not yet attempted to investigate whether lack of funding (rather than, e.g., regulatory approval) is a primary bottleneck to scaling up oral PrEP programs to population groups at substantial risk of acquiring HIV in sub-Saharan Africa.21

Focus of further investigation

We may revisit this investigation in the future to see whether more information relevant to the cost-effectiveness of oral PrEP programs in sub-Saharan Africa is available. To learn more about whether an oral PrEP program may be more cost-effective than our interim model suggests, we would initially focus on the following questions:

  • What is the total cost (per person per year) of the program?
  • What is the baseline HIV infection rate among populations targeted by the program?
  • For how many years are individuals or population groups expected to participate in the program?22

Our process

We conducted a brief review of the literature focusing on the Cochrane Library,23 WHO and UNAIDS materials on oral PrEP,24 systematic reviews on oral PrEP found through Google Scholar,25 and information on the current implementation of oral PrEP programs found through the PrEP Watch website.26

Sources

Document Source
Fonner et al. 2016 Source (archive)
Gates Foundation Jhpiego grant July 2016 Source (archive)
Gomez et al. 2013 Source (archive)
JHU Hub Bridge to Scale 2016 Source (archive)
Kahn, Marseille and Auvert 2006 Source (archive)
Okwundu et al. 2012 Source (archive)
PEPFAR DREAMS Source (archive)
PrEP Watch homepage Source (archive)
PrEP Watch Kenya Source (archive)
PrEP Watch Nigeria Source (archive)
PrEP Watch Oral PrEP Map Kenya 2016 Source (archive)
PrEP Watch South Africa Source (archive)
PrEP Watch Uganda Source (archive)
PrEP Watch Zimbabwe Source (archive)
UNAIDS Global AIDS Update 2016 Source (archive)
UNAIDS oral pre-exposure prophylaxis 2015 Source (archive)
UNAIDS Prevention Gap report 2016 Source (archive)
WHO Pre-exposure prophylaxis Source (archive)
WHO PrEP clinical guidelines 2015 Source (archive)
WHO PrEP policy brief 2015 Source (archive)
  • 1.
    • HIV epidemic and response estimates, global and by region, 2010 and 2015 table, New HIV Infections (all ages), UNAIDS Global AIDS Update 2016, Pg 2.
    • The sum of new HIV infections from Eastern and Southern Africa (960,000) and Western and Central Africa (410,000) is 1,370,000.
  • 2.

    "This review evaluated the effects of giving people at high risk for HIV infection drugs to prevent infection (called antiretroviral pre-exposure prophylaxis, or PrEP). We found six randomised controlled trials that assessed the effects of oral tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) versus placebo; TDF versus placebo, and daily TDF-FTC versus intermittent TDF-FTC." Okwundu et al. 2012, Pg 2.

  • 3.

    "Oral pre-exposure prophylaxis of HIV infection – PrEP – is the use of antiretroviral (ARV) drugs by people who do not have HIV infection in order to prevent the acquisition of HIV." WHO PrEP policy brief 2015, Pg 1.

  • 4.
    • WHO PrEP policy brief 2015:
      • "The World Health Organization (WHO) now recommends that people at substantial risk of HIV should be offered PrEP. In 2014 WHO recommended offering PrEP to men who have sex with men (MSM). On the basis of further evidence of the effectiveness and acceptability of PrEP, WHO has now broadened the recommendation to include all population groups at substantial risk of HIV infection. Offering PrEP should be a priority for populations with an HIV incidence of about 3 per 100 person-years or higher." Pg 1.
      • "Oral PrEP containing tenofovir disoproxil fumarate (TDF) should be offered as an additional prevention choice for people at substantial risk of HIV infection as part of combination HIV prevention approaches. Strong recommendation, high-quality evidence." Pg 1.
    • "Substantial risk of HIV infection is provisionally defined as HIV incidence around 3 per 100 person-years or higher in the absence of PrEP." WHO PrEP clinical guidelines 2015 Pg 53.
  • 5.
    • We found the website "PrEP Watch" (www.prepwatch.org), which tracks the implementation of PrEP programs around the world, linked in the "Partner links" section on the WHO's page on pre-exposure prophylaxis. WHO Pre-exposure prophylaxis.
    • "PrEP Watch was created and is maintained by AVAC, a non-profit organization based in New York that uses education, policy analysis, advocacy and a network of global collaborations to accelerate the ethical development and global delivery of new and emerging HIV prevention options as part of a comprehensive response to the HIV/AIDS pandemic." PrEP Watch homepage.
    • As of February 2017, PrEP Watch lists PrEP demonstration projects in sub-Saharan Africa in Nigeria, Uganda, Kenya, Zimbabwe, Botswana, and South Africa. PrEP Watch homepage. The oral PrEP "demonstration projects" listed in sub-Saharan Africa are:
      • "Research and Demonstration Projects: Nigeria is host to a PrEP demonstration project among serodiscordant couples at sites in Plateau, Edo and Cross River State. It is scheduled to run from late-2015 until late-2017." PrEP Watch Nigeria
      • "Research/Demonstration Projects: Uganda has been the site of trials and demonstration projects of daily oral PrEP in serodiscordant couples; PrEP is slated to be included in the PEPFAR-supported DREAMS initiative focused on young women and adolescent girls." PrEP Watch Uganda
      • "Research/Demonstration Projects: Kenya has been the site of trials and demonstration projects of daily oral PrEP in serodiscordant couples, heterosexual women, men who have sex with men and sex workers. PrEP is slated to be included in the PEPFAR-supported DREAMS initiative focused on young women and adolescent girls." PrEP Watch Kenya
      • "Research/Demonstration Projects: Zimbabwe is the site for the SAPPH-Ire PrEP demonstration project, looking at how best to roll out PrEP and ARV treatment to sex workers. Results are expected at the end of 2016. PrEP will also be incorporated into the PEPFAR-funded DREAMS initiative." PrEP Watch Zimbabwe
      • "Research/Demonstration Projects: South Africa hosted a site in the phase III iPrEx trial, and the open label extension of iPrEx in MSM and is hosting demonstration projects of daily oral PrEP in men who have sex with men and sex workers. PrEP is slated to be included in the PEPFAR-supported DREAMS initiative focused on young women and adolescent girls." PrEP Watch South Africa
  • 6.
    • We focused our initial investigation for this page on PrEP programs in sub-Saharan Africa due to our impression that these programs were likely to be most cost-effective due to high HIV incidence rates, and due to the possibility of scaling up PrEP to larger population groups. It's our understanding that some groups of adolescent girls and young women in Southern Africa have high enough HIV incidence rates to qualify as having "substantial risk" (an incidence rate of new HIV infections of 3 per 100 person-years or more).
    • "Offering PrEP is expected to be cost-effective where the incidence of HIV is greater than 3 per 100 person-years and perhaps also at lower incidence. Incidence as high as 3 per 100 person-years remains common among young women in some settings in southern Africa, among some sex workers in Africa and among MSM in many countries." WHO PrEP policy brief 2015, Pg 2.
    • HIV epidemic and response estimates, global and by region, 2010 and 2015 table, New HIV Infections (all ages), UNAIDS Global AIDS Update 2016, Pg 2.
    • In Asia, demonstration projects are listed in Thailand and India. In South America, demonstration projects are listed in Brazil and Peru. PrEP is also available in the US, Canada, Australia, and some countries in Europe. PrEP Watch homepage
  • 7.

    WHO PrEP clinical guidelines 2015:

    • "HIV testing is required before PrEP is offered and regularly while PrEP is taken. People who test HIV negative but report high risk can be linked to prevention services where the potential for PrEP use can be assessed. HIV testing is required before PrEP is offered and should be conducted regularly (e.g. every three months) while PrEP is taken." Pg 58.
    • "Ensure access to accurate knowledge and information about PrEP and early treatment by strengthening the capacity of community-based organizations in educating and training their communities about the use of PrEP." Pg 58.
    • "All PrEP trials tested renal function using serum creatinine before starting PrEP and at least quarterly during PrEP use, and these test results were used to exclude participants from trials and to stop study medication if they had abnormal results that were confirmed by repeat testing. Renal function returned to normal after stopping PrEP except for a few people who had underlying comorbidities such as systemic hypertension and diabetes mellitus. Unless more data become available, creatinine testing is preferred before starting PrEP and quarterly during PrEP use for the first 12 months, then annually thereafter. Point-of-care and laboratory-based assays for creatinine and HIV are available." Pg 59.
    • "Hepatitis B virus (HBV) is endemic in many parts of the world where HIV is transmitted. The medications used for PrEP are active against HBV. Withdrawal of active therapy against HBV can lead to virological and clinical relapse. Clinical relapse did not occur during or after PrEP use in trials that included people with chronic HBV (6,8) . These trials excluded people with clinical liver cirrhosis and people with significant elevations in liver function tests. Testing PrEP users for hepatitis B surface antigen (HBsAg) is preferred. People with detectable HBsAg and alanine transaminase (ALT) elevated more than twice the upper limit of normal or clinical signs of cirrhosis could benefit from long-term therapy for HBV." Pg 59.
    • "Support for adherence should include information that PrEP is highly effective when used. Brief client-centred counselling that links daily medication use with a daily habit (such as waking up, going to sleep or a regular meal) may be helpful. Special programmes to facilitate adherence among particular groups – such as young people and women – may be needed." Pg 59.
      • 8.

        Okwundu et al. 2012, Pg 1-2

      • 9.

        "Mutua 2010 was conducted in Kenya, and Thigpen 2012 was conducted in Botswana. Four of the studies (Baeten 2012 ; Grant 2010; Van Damme 2012 and Peterson 2007) were multinational trials. Baeten 2012 study was conducted in Kenya and Uganda; Grant 2010 study was conducted in Peru, Ecuador, South Africa, Brazil, Thailand and the United States of America; Peterson 2007 study was conducted in Cameroon, Ghana and Nigeria; and Van Damme 2012 study was conducted in Kenya, South Africa, Tanzania and Zimbabwe." Okwundu et al. 2012, Pg 9

      • 10.
        • Description and names of the six trials included in Okwundu et al. 2012:
          • "The studies involved HIV-uninfected participants from different risk groups: 2499 men who have sex with men aged 18 years and above (Grant 2010), 936 high risk women age 18 to 35 years (Peterson 2007), 144 high-risk men and women (67 men who have sex with men, 5 female sex workers and 72 serodiscordant couples: 36 men and 36 women) aged 18 to 49 years (Mutua 2010), 4758 serodiscordant couples (men and women aged 18 to 65 years) (Baeten 2012), 1200 heterosexual men and women aged 18-39 (Thigpen 2012) and 2120 high-risk women aged of 18 to 35 years (Van Damme 2012). The participants in Peterson 2007 trial lived in areas within each city that were considered to be at high risk for HIV transmission and were also at high risk of acquiring HIV infection by virtue of having three or more coital acts per week and four or more sexual partners per month. Mutua 2010 was conducted in Kenya, and Thigpen 2012 was conducted in Botswana. Four of the studies (Baeten 2012 ; Grant 2010; Van Damme 2012 and Peterson 2007) were multinational trials. Baeten 2012 study was conducted in Kenya and Uganda; Grant 2010 study was conducted in Peru, Ecuador, South Africa, Brazil, Thailand and the United States of America; Peterson 2007 study was conducted in Cameroon, Ghana and Nigeria; and Van Damme 2012 study was conducted in Kenya, South Africa, Tanzania and Zimbabwe." Pg 9
        • Fonner et al. 2016:
          • "No. of studies" listed as "RCTs comparing PrEP with placebo" is 10. Pg 1978, Table 2.
          • The 10 RCTs comparing PrEP with placebo are listed as: Bangkok Tenofovir Study, FEM-PrEP, iPrEx, IAVI Kenya Study, IAVI Uganda Study, Partners PrEP study, Project PrEPare, TDF2, VOICE, and West African Safety Study. Pgs 1976-1977, Table 1.
        • Based on the location, study population, and number of participants listed in Fonner et al. 2016, Table 1 (Pgs 1976-1977), the six trials included in Okwundu et al. 2012 (listed above) all appear to be included: Grant 2010 (iPrEx), Peterson 2007 (West Africa Safety Study), Mutua 2010 (IAVI Kenya Study), Baeten 2012 (Partners PrEP study), Thigpen 2012 (TDF2), and Van Damme 2012 (FEM-PrEP). The four placebo-controlled RCTs analyzed in Fonner et al. 2016 that were not included in Okwundu et al. 2012 are: Bangkok Tenofovir Study, IAVI Uganda Study, Project PrEPare, and VOICE.
      • 11.

        Fonner et al. 2016, Pg 1978, Table 2, "RCTs comparing PrEP with placebo"

      • 12.

        "The overall quality of evidence on the effectiveness of PrEP for preventing HIV in high-risk individuals can be described as moderate quality. We downgraded the quality of evidence by one level on account of instability of results since there are fewer than 200 events per arm." Okwundu et al. 2012, Pg 16.

      • 13.
        • "Four studies that compared TDF-FTC with placebo reported HIV incidence (Baeten 2012; Van Damme 2012; Grant 2010; Thigpen 2012). The meta-analysis revealed significantly lower HIV incidence in participants who received TDF-FTC compared to those who received placebo (Mantel-Haenzael random effects RR (RRMHRE) 0.49; 95% CI 0.28 to 0.85; 8918 participants). There was substantial statistical heterogeneity (I2 =77%, p=0.005) (Figure 4; Analysis 1.1). Two RCTs that compared TDF with placebo reported HIV incidence. The meta-analysis of these two RCTs (Peterson 2007; Baeten 2012) demonstrated that high-risk individuals treated with TDF showed lower HIV incidence than those on placebo (RRMHRE 0.33; 95% 0.20 to 0.55; 4027 par- ticipants). There was no significant statistical heterogeneity (I2 = 0%, p=0.97) (Figure 5; Analysis 2.1)." Okwundu et al. 2012, Pg 11.
        • "Across placebo-controlled trials (Table 2a, Fig. 2), results from meta-analysis demonstrated a 51% reduction in risk of HIV infection comparing PrEP with placebo [risk ratio = 0.49, 95% confidence interval (CI): 0.33 – 0.73, P = 0.001]. Results from meta- regression suggest adherence was a significant moderator of PrEP effectiveness (regression coefficient = 0.02, P < 0.001) (Table 2a, Fig. 2). When stratified by adherence, overall heterogeneity was greatly reduced. PrEP was most effective in studies with high adherence, where HIV infection risk was reduced by 70% (risk ratio = 0.30, 95% CI: 0.21 – 0.45, P < 0.001). PrEP also significantly reduced infection risk in studies with moderate adherence levels, but showed no effect in studies with low adherence (risk ratio = 0.95, 95% CI: 0.34–1.23, P = 0.70)." Fonner et al. 2016, Pg 1975
      • 14.
        • In 2016, UNAIDS reported that the number of people on PrEP outside of the United States was small:
        • "The number and scope of PrEP activities is increasing globally, while the scale and coverage outside the United States of America remain limited. In June 2016 an estimated 60 000 people were enrolled on PrEP, the majority of whom were in the United States." UNAIDS Prevention Gap report 2016, Pg 64.
        • The two ongoing PrEP programs in sub-Saharan Africa we have seen that appear to be large-scale (i.e., not a small pilot project or an extension of a research trial) are the DREAMS partnership, which is focused on several HIV prevention strategies for young women (including PrEP) in several countries in sub-Saharan Africa and is funded by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), the Bill and Melinda Gates Foundation, and other funders, and "Bridge to Scale," a PrEP scale-up program targeting 20,000 individuals in Kenya, led by Jhpiego.
          • "Jhpiego, a global health nonprofit and Johns Hopkins University affiliate, will scale up a highly effective HIV prevention strategy—a daily dose of an antiretroviral pill for highly vulnerable individuals that reduces their chances of contracting the virus.

            The Bill & Melinda Gates Foundation awarded Jhpiego $22.3 million over four years to scale up oral pre-exposure prophylaxis, known as PrEP, that studies have shown is as effective at preventing HIV as oral contraceptives are at preventing pregnancy when taken as directed.

            Working in strong partnership with the government of Kenya, Jhpiego will direct the Bridge to Scale project aimed at reaching 20,000 Kenyans who are most vulnerable to HIV infection. That includes adolescent girls and young women, among others, many of whom have difficulty accessing HIV prevention and treatment services because of stigma and cultural and social barriers." JHU Hub Bridge to Scale 2016

          • "With support from the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR), the Bill & Melinda Gates Foundation, Girl Effect, Johnson & Johnson, Gilead Sciences, and ViiV Healthcare, DREAMS is delivering a core package that combines evidence-based approaches that go beyond the health sector, addressing the structural drivers that directly and indirectly increase girls’ HIV risk, including poverty, gender inequality, sexual violence, and a lack of education." PEPFAR DREAMS
          • "Research/Demonstration Projects: Uganda has been the site of trials and demonstration projects of daily oral PrEP in serodiscordant couples; PrEP is slated to be included in the PEPFAR-supported DREAMS initiative focused on young women and adolescent girls." PrEP Watch Uganda
          • "Research/Demonstration Projects: Kenya has been the site of trials and demonstration projects of daily oral PrEP in serodiscordant couples, heterosexual women, men who have sex with men and sex workers. PrEP is slated to be included in the PEPFAR-supported DREAMS initiative focused on young women and adolescent girls." PrEP Watch Kenya
          • "Research/Demonstration Projects: Zimbabwe is the site for the SAPPH-Ire PrEP demonstration project, looking at how best to roll out PrEP and ARV treatment to sex workers. Results are expected at the end of 2016. PrEP will also be incorporated into the PEPFAR-funded DREAMS initiative." PrEP Watch Zimbabwe
          • "Research/Demonstration Projects: South Africa hosted a site in the phase III iPrEx trial, and the open label extension of iPrEx in MSM and is hosting demonstration projects of daily oral PrEP in men who have sex with men and sex workers. PrEP is slated to be included in the PEPFAR-supported DREAMS initiative focused on young women and adolescent girls." PrEP Watch South Africa
      • 15.

        WHO PrEP clinical guidelines 2015

        • "The risk of drug resistance to FTC was low overall (11 people with FTC- or TDF-resistant HIV infection among 9222 PrEP users, or 0.1%), and this occurred mainly among people who were acutely infected with HIV when initiating PrEP: 7 people of the 11 with FTC- or TDF-resistant HIV infection among 9222 PrEP users. The proportion of people with drug-resistant HIV did not differ in the PrEP and placebo groups among everyone at risk, although the number of events was low (n = 6 people infected). Multiple HIV infections (8–50) were averted for every case of FTC resistance associated with starting PrEP in the presence of acute HIV infection (16) . Modelling the HIV drug resistance resulting from ART is predicted to far exceed that resulting from PrEP (23). Although mathematical models inform the risk of resistance, their results rely on data from clinical trials and make assumptions about the risk of selection of drug-resistant virus during PrEP. How implementation of PrEP on a large scale affects resistance overall is unknown. Active surveillance during PrEP scale up may therefore be warranted." Pg 55.
        • "Several studies noted subclinical declines in renal functioning and bone mineral density among PrEP users (20–22) . These subclinical changes did not result in clinical events and were not progressive over time." Pg 55.
      • 16.
        • See our cost-effectiveness analysis for oral PrEP programs here.
        • In our "best guess" scenario, we roughly estimate that the cost to prevent an HIV infection through oral PrEP programs is $15,877. For our "optimistic" scenario, we estimate that it costs $5,126 per HIV infection prevented by oral PrEP programs in sub-Saharan Africa.
        • Our most up-to-date estimate of the cost to prevent an HIV infection through voluntary medical male circumcision (VMMC) is $2,301. We have not yet (as of July 2017) published our calculations for this estimate (for our previous estimates, see our VMMC intervention report).
        • For our best guess scenario for oral PrEP, we roughly estimate that VMMC is 10.4 times as cost-effective at preventing HIV infections than oral PrEP ($23,816 / $2,301 = 10.4). For our optimistic scenario for oral PrEP, we roughly estimate that VMMC is 3.3 times as cost-effective at preventing HIV infections than oral PrEP ($7,689 / $2,301 = 3.3).
      • 17.

        "The generic fixed-dose TDF + FTC combination is available for US$ 78 per person per year and generic TDF for US$ 43 per person per year. Branded TDF + FTC costs from US$ 3800 to US$ 10 200 per person per year in high-income countries, and the lowest cost of branded TDF is US$ 91 per person per year." UNAIDS oral pre-exposure prophylaxis 2015, Pg 10

      • 18.
        • See Pretorius ($150 per person per year), Hallet ($150-$250 per person per year), and Cremin ($252 per person per year), Gomez et al. 2013, Pg 8, Table 4.
        • We exclude Abbas and Alistar since only drug costs are included, and we exclude Williams and Walensky since they model the costs of topical rather than oral PrEP programs.
      • 19.
        • The Bill & Melinda Gates Foundation awarded Jhpiego a grant of $22.3 million to lead the "Bridge to Scale" project in Kenya, which is intended to reach 20,000 individuals from high-risk groups (adolescent girls and young women, men who have sex with men, and sex workers) over four years. The primary purpose of the project appears to be PrEP scale-up.
          • "Date: July 2016
            Purpose: to demonstrate and document an effective model for how oral Pre-exposure prophylaxis (PrEP) can be scaled up as an HIV-prevention intervention in low-resource settings
            Amount: $22,339,754" Gates Foundation Jhpiego grant July 2016
          • "The Bill & Melinda Gates Foundation awarded Jhpiego $22.3 million over four years to scale up oral pre-exposure prophylaxis, known as PrEP, that studies have shown is as effective at preventing HIV as oral contraceptives are at preventing pregnancy when taken as directed.

            Working in strong partnership with the government of Kenya, Jhpiego will direct the Bridge to Scale project aimed at reaching 20,000 Kenyans who are most vulnerable to HIV infection. That includes adolescent girls and young women, among others, many of whom have difficulty accessing HIV prevention and treatment services because of stigma and cultural and social barriers.

            The key goals of the project—the first of its kind to deliver PrEP widely across a health system while promoting a sustainable service delivery model—is to learn and develop new ways of ensuring that lifesaving interventions like this one reach those most likely to benefit, and to assess barriers to services as health providers integrate delivery of such interventions into routine health care practices." JHU Hub Bridge to Scale 2016

          • Targeted population groups for the "Bridge to Scale" project are listed as adolescent girls and young women, men who have sex with men, female sex workers, and male sex workers. PrEP Watch Oral PrEP Map Kenya 2016, Kenya - Oral PrEP Organizations sheet, cell E35.
          • See our PrEP cost-effectiveness analysis here for more details.
        • 20.
          • Our initial cost-effectiveness analysis suggests that oral PrEP programs may be 0.4 times as cost-effective as cash transfers to very poor individuals. See our PrEP cost-effectiveness analysis here, "Best guess" sheet, for more details.
          • See our "Your Dollar Goes Further When You Fund the Right Program" page for details on cash transfers as our cost-effectiveness baseline.
          • With optimistic assumptions (see "Optimistic" sheet here), we estimate that oral PrEP programs may be roughly 1.1 times as cost-effective as cash transfer programs. We do not consider this to be substantially more cost-effective than cash, due to significant uncertainty in our cost-effectiveness models, and we are not certain how realistic our optimistic assumptions may be.
        • 21.

          “In June 2016 an estimated 60 000 people were enrolled on PrEP, the majority of whom were in the United States. A significant but unquantifiable number of people are accessing PrEP through less regulated means, for example via the internet. The rapid establishment of government-regulated programmes will improve the monitoring and evaluation of PrEP’s use and its impact on the epidemic. Considerable additional effort will be needed to attain the new global target of reaching three million people at substantial risk of HIV infection with PrEP by 2020.

          PREVENTION GAPS

          • PrEP is just getting off the ground: progress towards the 2020 PrEP target stands at 2%.
          • Availability and awareness is limited.
          • Regulatory approval is limited to seven countries.
          • PrEP provision should be sensitive to the context of the populations at risk including stigmatization, criminalization and intimate partner violence.”

          UNAIDS Prevention Gap report 2016, Pg 64

        • 22.
          • We would guess that some populations (e.g., some groups of adolescent girls and young women, see quote in bullet point below) may have a high risk of acquiring HIV only for a relatively short period of their lives, while other populations may be at high risk of acquiring HIV for extended periods. We roughly expect that a program focused on a short-term high-risk population only requiring PrEP for a limited period may be more cost-effective than a program focused on long-term high-risk groups, but we have not yet investigated this issue in depth.
          • "Young women aged 15–24 years are at particularly high risk of HIV infection, accounting for 20% of new HIV infections among adults globally in 2015, despite accounting for just 11% of the adult population. In sub-Saharan Africa, young women accounted for 25% of new HIV infections among adults and women accounted for 56% of new HIV infections among adults. Gender inequalities, including gender-based violence, exacerbate women’s and girls’ physiological vulnerability to HIV and block their access to HIV services. Young people are denied the information and the freedom to make free and informed decisions about their sexual health, with most lacking the knowledge required to protect themselves from HIV. The impact of these barriers is strongest in high-prevalence settings, predominantly in eastern and southern Africa." UNAIDS Prevention Gap report 2016, Pg 7.
        • 23.

          Okwundu et al. 2012

        • 24.
        • 25.

          Fonner et al. 2016

        • 26.