Estimating the impact of HIV combination prevention in men who have sex with men,the Bangkok MSM Cohort Study,Thailand

Abstract

In Thailand, pre-exposure prophylaxis (PrEP) is recommended for human immunodeficiency virus (HIV) prevention among at-risk men who have sex with men (MSM). We modeled the impact of PrEP and condom use as independent and combined interventions on the estimated number of HIV infections among a hypothetical population of 10,000 MSM in Bangkok, Thailand. Our model demonstrated a 92% (95% confidence interval 89.7, 94.2) reduction in HIV infections among Thai MSM who took daily PrEP and self-reported using condoms correctly and consistently (100% condom use). Increased use of PrEP and condoms likely would have a substantial impact on the HIV epidemic in Thailand.

Keywords

Pre-exposure prophylaxis HIV condom men who have sex with men Bangkok Thailand

Background

Despite successes in human immunodeficiency virus (HIV) prevention in Thailand, including the elimination of mother-to-child HIV transmission in 2016,¹ high rates of HIV transmission continue to occur among men who have sex with men (MSM) and transgender women (TGW).² During 2011–2014, HIV prevalence among MSM in Bangkok, Thailand, was about 30%,³ and HIV incidence was 4.8 per 100 person-years.² Daily oral pre-exposure prophylaxis (PrEP) has high efficacy to prevent HIV among MSM.⁴ The Pre-exposure Prophylaxis Initiative (iPrEX) trial, which included a site in Thailand, found a 44% reduction in new HIV infections among MSM and TGW randomized to PrEP compared to those randomized to placebo. Furthermore, the trial found a 92% reduction in new HIV infections among participants with a detectable level of a study drug in plasma or peripheral-blood mononuclear cells.⁴ Since 2014, the Thailand Ministry of Public Health has recommended PrEP for high-risk individuals, including MSM.⁵ Thailand was among the first Southeast Asian countries to implement PrEP.⁶ Although there has been strong interest in PrEP among Thai MSM and TGW, challenges remain to achieve broad implementation.⁶ At the present time (September 2019), PrEP is not offered free of charge under the Universal Health Scheme in Thailand.⁵ More data are needed to support PrEP policies and implementation, including the impact of PrEP on the HIV epidemic in Thailand.

Available mathematical models have highlighted the cost-effectiveness and positive benefits of PrEP among MSM in terms of HIV infections averted.⁷,⁸ For example, Suraratdecha et al.⁹ recently evaluated the cost-effectiveness of PrEP among MSM in Thailand using a compartment model with data from the Test, Treat, and Prevent Programme, which included a PrEP implementation project conducted at two Thai sites. The model found that a PrEP strategy targeting high-risk MSM is the most cost-effective intervention. Although dynamic models which account for transmission between partners may be the strongest modeling approach,⁷ static, Markov, or deterministic models can also provide needed data to guide policy considerations.⁸ One deterministic model by Smith et al. suggested that daily PrEP further reduced HIV incidence when added to consistent and correct condom use.⁸ There are few models using data from Thailand to inform policies and practices.⁹ Data on adherence and uptake from PrEP demonstration projects in Thailand, as well as cost-effectiveness and impact models using attributes of the Thai epidemic lend support to policy considerations, as Thailand attempts to meet UNAIDS goals to end the AIDS pandemic by 2030.¹⁰ Further data showing PrEP impact could provide additional impetus and support for reducing barriers to PrEP use for at-risk MSM in Thailand.

Methods

We used mathematical methods similar to that by Smith et al. to assess the expected number of HIV infections in a hypothetical population of 10,000 MSM in Thailand with no PrEP or condom use, and those with varying levels of adherence to combination prevention.⁸ We take into account both PrEP and condom use, as the Thailand policy for PrEP supports combination prevention approaches.⁶ We used the best available data on local behavioral risk and HIV incidence from the Bangkok MSM Cohort Study (BMCS).¹¹

In brief, we used three parameters: HIV incidence, PrEP effectiveness stratified by self-reported adherence, and condom effectiveness with any insertive or receptive anal sex, also stratified by self-reported adherence. Assuming that PrEP and condom use effectiveness are independent, the estimated annual incidence ( $I_{i j}$ ) for the $i$ th condom effectiveness class (always, sometimes, never) and $j$ th PrEP effectiveness class ( $\geq$ 90% use, 1–49% use, never) was calculated as follows

I_{i j} = (I) {R R}_{i}^{C} {R R}_{j}^{P}

where

I

is the baseline incidence and

R R

is the relative risk of HIV infection for a given condom effectiveness class (

C

) or PrEP effectiveness class (

P)

with ‘never’ as the reference category.

We estimated the expected number of HIV infections for a hypothetical sample of 10,000 Thai MSM living in Bangkok over one year for each level of PrEP and condom use adherence. Variance estimates and confidence intervals (CI) for incidence were calculated using the method described by Smith et al., which assumes that PrEP and condom use effectiveness are independent.⁸

Parameters – Table 1

HIV incidence

We used the overall annual HIV incidence estimate from BMCS, a 60-month longitudinal cohort study of adult Thai MSM and TGW conducted between April 2006 and December 2015. BMCS assessed HIV prevalence, incidence, and risk factors among MSM in Bangkok, Thailand, by conducting HIV testing at each four-month visit.¹¹ PrEP first became available for purchase in Bangkok in December 2014⁶ but widespread implementation did not occur until 2016; PrEP was not available at Silom Community Clinic until 2016. As most BMCS participants had exited the study by that time, HIV incidence estimates in this cohort are unlikely to have been impacted by PrEP use.

Table 1.

Summary of the model parameters.

Parameters	HIV incidence	PrEP effectiveness	Condom effectiveness
Measurement	BMCS Prospective cohort with HIV testing at each four-month visit for a total of 60 months	iPrEX Self-reported medication adherence	Smith et al.⁸ Self-reported method adherence
Estimates	5.9 per 100 PY (95% CI 5.2, 6.8)	≥90% PrEP use: 73% (95% CI 41, 88) 1–49% PrEP use: 32% (95% CI –41, 67)	Always: 70.5% (95% CI 58.2, 79.2) Sometimes: 8.0% (95% CI –24.8, 32.1)
Characteristics	The largest and longest high-risk MSM cohorts in Thailand (for example, 40% had ≥6 partners in past four months, anal intercourse without a condom in past four months = 60%)	A phase 3 clinical trial to evaluate the efficacy of PrEP in high-risk MSM (for example, average no. of partners in past 12 wk = 12, receptive anal intercourse without a condom in past 12 wk = 60%)	The study investigated the effectiveness according to consistency of use during penile–anal intercourse among MSM, based on data from two large prospective HIV prevention trials that assessed condom use and HIV serostatus at standard intervals over multiple years

iPrEP: Pre-exposure Prophylaxis Initiative; BMCS: Bangkok MSM Cohort Study; CI: confidence interval; PrEP: pre-exposure prophylaxis; PY: person-years.

PrEP effectiveness by self-reported medication adherence

We used data from the iPrEX clinical trial of PrEP use among MSM to estimate PrEP effectiveness.⁴ In a modified intention-to-treat analysis from iPrEX, a combination measure of adherence including self-reported medication adherence, pills dispensed, and pills returned over scheduled visits resulted in a PrEP efficacy of 32% (95% CI –41, 67) among MSM with adherence less than 50%, and 73% (95% CI 41, 88) among MSM with adherence of 90% or greater.

Condom effectiveness by self-reported method adherence

We estimated condom effectiveness using published data on self-reported condom use from two prospective HIV prevention trials (i.e. the VAX 004 trial from 1998 to 1999 and the EXPLORE trial from 1999 to 2000) among MSM with at least one HIV-positive partner, because the risk of per-act HIV transmission via sexual exposure is highest for receptive anal intercourse.¹² In those reporting always using condoms, condom effectiveness was 70.5% (95% CI 58.2, 79.2) but only 8.0% (95% CI –24.8, 32.1) in those sometimes using condoms (condom use 1%–99%), compared with those never using condoms during any insertive or receptive anal sex.¹³

Results

For every 10,000 Thai MSM in Bangkok who never use either PrEP or condoms, we estimate that 590 (95% CI 520, 680) new HIV infections would occur each year. Among those who use condoms consistently and correctly, and have ≥90% daily PrEP use, only 46 (95% CI 19, 110) new HIV infections would occur each year, a 92% reduction in new HIV infections. MSM who do not take PrEP (but use condoms consistently and correctly) would have 73% fewer HIV infections if they also began taking daily PrEP with ≥90% adherence (171 per 10,000 MSM not using PrEP versus 46 per 10,000 MSM reporting adherence to both prevention interventions) (Table 2). MSM with high adherence to PrEP (≥90% daily PrEP use), but do not use condoms, would similarly have 71% fewer HIV infections if they started to use condoms consistently and correctly (159 per 10,000 MSM adherent to PrEP alone versus 46 per 10,000 MSM reporting high adherence to both PrEP and condoms).

Table 2.

Estimated number of annual HIV infections among 10,000 Thai men who have sex with men stratified by adherence to pre-exposure prophylaxis (PrEP) and condom use, Bangkok, Thailand.

Number of HIV infections (95% CI)
	≥90% PrEP use	1–49% PrEP use	Never used PrEP
Self-reported condom use
Always	46 (19, 110)	116 (52, 260)	171 (121, 242)
Sometimes	147 (62, 344)	369 (168, 811)	543 (400, 736)
Never	159 (72, 353)	401 (194, 829)	590 (520, 680)

Note: ‘Always’ refers to 100% condom use. ‘Sometimes’ refers to 1–99% condom use. ‘Never’ refers to 0% condom use. Data for 50–89% PrEP use are not available. HIV incidence per 100 person-years 5.9 (95% CI 5.2, 6.8) among MSM participating in the Bangkok MSM Cohort Study (BMCS) in Bangkok, Thailand. CI: confidence interval; PrEP: pre-exposure prophylaxis.

Given an estimated 33,881 sexually active MSM living in Bangkok in 2016,¹⁴ our analysis finds that high adherence to both PrEP and condoms would prevent 1843 HIV infections per year in Bangkok alone.

Discussion

This is one of the first models of PrEP impact using HIV incidence data from Bangkok, Thailand. Although this model does not include measures of transmission dynamics, this analysis suggests that there likely would be substantially fewer HIV infections if MSM take both daily PrEP and use condoms consistently and correctly (combination prevention) compared to non-PrEP users who do not use condoms. A recent compartment model also showed that providing PrEP to MSM would be cost-effective with greatest cost-effectiveness among high-risk MSM.⁹ Although not all at-risk MSM may choose to adopt combination prevention strategies, the impact of combination prevention on the HIV epidemic in Thailand could be substantial, and collectively these modeling data support policies to enhance provision and uptake of combination prevention strategies, including PrEP provided at no charge to those at risk for HIV infection.

Public health interventions often have competing demands for government and policy makers, and models of cost-effectiveness and intervention impact can provide critical information on the relative impact (or lack of impact) for different public health strategies. Thailand has adopted a goal of zero new HIV infections by 2030 and is supporting the UNAIDS 95-95-95 goals for HIV testing and treatment; however; there are no set targets for PrEP implementation in the region. Widespread PrEP implementation will be important to reduce new HIV infections among MSM, especially in the young (i.e. ≤21 years), who remain at the highest risk.¹⁵ Prior evaluations have demonstrated that despite reaching 90-90-90 targets for the HIV treatment continuum, goals for averting new infections cannot be met without also increasing use of PrEP and other primary prevention methods.¹⁵

There are limitations to our assessment. First, our model assumes independent effects of PrEP and condom use on HIV acquisition rates; this assumption may not be true if PrEP users decrease condom use (risk compensation). Second, we used a simple deterministic model limited to information that was available (i.e. PrEP efficacy among MSM with 50–89% PrEP use was not available), and a more rigorous approach using a dynamic model would better account for transmission effects of the interventions. We did not perform a sensitivity analysis using the observed data from a real world setting and this warrants the validity of the model. Although PrEP may also have substantial benefit among TGW as well as MSM, we had few TGW in the BMCS to assess TGW separately in our model. The estimated number of sexually active MSM living in Bangkok may be underestimated and therefore underestimating the benefits of PrEP and condom use. Additionally, although there are particular factors from the BMCS such as drug use and young age that were found to increase HIV incidence substantially, estimates of HIV incidence among MSM subgroups are not currently available. However, it is reasonable to assume that combination prevention approaches would have a substantial impact for these at-risk populations as well. Finally, our model did not account for the impact of treatment as prevention on reducing HIV incidence, and this should be included in future models.

In conclusion, our model showed that effective programs that support high PrEP and condom use for MSM at risk could have a substantial impact on the HIV epidemic in Thailand. Additional modeling efforts to address PrEP impact in TGW and adolescent and young MSM in Thailand would be particularly important to provide data to support policies and practices for HIV prevention.

Footnotes

Acknowledgments

The authors kindly acknowledge and are thankful for the support of the Thailand Ministry of Public Health-U.S. Centers for Disease Control and Prevention Collaboration, the Silom Community Clinic (Silom Community Clinic @TropMed), the Department of Disease Control, Thailand Ministry of Public Health, the Rainbow Sky Association of Thailand (RSAT), and the Service Workers in Group Foundation (SWING). We dedicate this work to the memory of Supaporn Chaikummao, RN and Patrick J Flaherty who devoted their professional lives to the care of persons at risk of HIV infection. The findings and conclusions reported in this paper are those of the authors and do not represent the views of the U.S. Centers for Disease Control and Prevention. These data were presented in part during the 22nd International AIDS Conference, Amsterdam, Netherlands, July 2018 (abstract # TUAC0201).

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the U.S. Centers for Disease Control and Prevention.

ORCID iDs

Sarika Pattanasin

Eileen F Dunne

References

Lolekha

Boonsuk

Plipat

, et al. Elimination of mother-to-child transmission of HIV – Thailand. MMWR Morb Mortal Wkly Rep 2016; 65: 562–566.

Holtz

Wimonsate

Mock

, et al. Why we need pre-exposure prophylaxis: incident HIV and syphilis among men, and transgender women, who have sex with men, Bangkok, Thailand, 2005–2015. Int J STD AIDS 2019; 30: 430–439.

Wimonsate

Pattanasin

Ungsedhapand

, et al. Repeat HIV testing among HIV-uninfected men who have sex with men attending Silom Community Clinic, Bangkok, 2011–2014. Int J STD AIDS 2018; 29: 1417–1423.

Grant

Lama

Anderson

, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010; 363: 2587–2599.

Thailand MoPH. Thailand national guidelines on HIV/AIDS treatment and prevention. Thailand: Thailand MoPH, 2017.

Colby

Srithanaviboonchai

Vanichseni

, et al. HIV pre-exposure prophylaxis and health and community systems in the Global South: Thailand case study. J Int AIDS Soc 2015; 18: 19953.

Jenness

Goodreau

Rosenberg

, et al. Impact of the centers for disease control’s HIV preexposure prophylaxis guidelines for men who have sex with men in the United States. J Infect Dis 2016; 214: 1800–1807.

Smith

Herbst

Rose

CE.

Estimating HIV protective effects of method adherence with combinations of preexposure prophylaxis and condom use among African American men who have sex with men. Sex Transm Dis 2015; 42: 88–92.

Suraratdecha

Stuart

Manopaiboon

, et al. Cost and cost-effectiveness analysis of pre-exposure prophylaxis among men who have sex with men in two hospitals in Thailand. J Int AIDS Soc 2018; 21: e2512.

10.

UNAIDS. Update: Thailand launches new national strategy to end the AIDS epidemic by 2030. Geneva: UNAIDS, 2017.

11.

van Griensven

Thienkrua

McNicholl

, et al. Evidence of an explosive epidemic of HIV infection in a cohort of men who have sex with men in Thailand. AIDS 2013; 27: 825–832.

12.

Patel

Borkowf

Brooks

, et al. Estimating per-act HIV transmission risk: a systematic review. AIDS 2014; 28: 1509–1519.

13.

Smith

Herbst

Zhang

, et al. Condom effectiveness for HIV prevention by consistency of use among men who have sex with men in the United States. J Acquir Immune Defic Syndr 2015; 68: 337–344.

14.

BMA. Estimation of HIV/AIDS epidemic in Bangkok, Thailand 2016–2030. London: BMA, 2016 (in Thai).

15.

van Griensven

Guadamuz

de Lind van Wijngaarden

, et al. Challenges and emerging opportunities for the HIV prevention, treatment and care cascade in men who have sex with men in Asia Pacific. Sex Transm Infect 2017; 93: 356–362.