It is well established that adherence to effective antiretroviral treatment (ART) is essential for viral control and hence survival in HIV/AIDS [1 Wood E, Hogg RS, Yip B, Harrigan PR, O'Shaughnessy MV, Montaner JS. Effect of medication adherence on survival of HIV-infected adults who start highly active antiretroviral therapy when the CD4+ cell count is 0.200 to 0.350 x 10(9) cells/L Ann Intern Med 2003; 139: 810-6.]. Earlier studies have shown that ART requires strict dosing schedules for it to be maximally effective, i.e. adherence of >95% is needed for optimal viral suppression in patients taking protease inhibitor-based regimens [2 Paterson DL, Swindells S, Mohr J, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection Ann Intern Med 2000; 133: 21-30.]. More recent studies suggest that adherence of 80% (or even less in some patients) may be sufficient for suppression in the current era of more effective ART, particularly with a longer duration on ART[3 Bangsberg DR. Less than 95% adherence to nonnucleoside reverse-transcriptase inhibitor therapy can lead to viral suppression Clin Infect Dis 2006; 43: 939-41., 4 Rosenblum M, Deeks SG, van der Laan M, Bangsberg DR. The risk of virologic failure decreases with duration of HIV suppression, at greater than 50% adherence to antiretroviral therapy PLoS One 2009; 4: e7196.].

Having a low serum viral load (VL) is known to be associated with much lower risks of transmission of HIV [5 Quinn TC, Wawer MJ, Sewankambo N, et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group N Engl J Med 2000; 342: 921-., 6 Donnell D, Baeten JM, Kiarie J, et al. Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis Lancet 2010; 375: 2092-8.]. However it has been shown that a low plasma viral load does not always correlate with a low genital HIV viral load so transmission could still potentially occur in this situation [7 Cu-Uvin S, DeLong AK, Venkatesh KK, et al. Genital tract HIV-1 RNA shedding among women with below detectable plasma viral load AIDS 2010; 24: 2489-97.-9 Halfon P, Giorgetti C, Khiri H, et al. Semen may harbor HIV despite effective HAART: another piece in the puzzle PLoS One 2010; 5: e10569.]. Yet several studies have shown none or few heterosexual transmissions when a partner is on ART, including a recent randomised controlled international study, HPTN052 showing a 96% transmission in discordant couples if the infected person takes ART [10 Attia S, Egger M, Muller M, Zwahlen M, Low N. Sexual transmission of HIV according to viral load and antiretroviral therapy: systematic review and meta-analysis AIDS 2009; 23: 1397-404., 11 Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 Infection with Early Antiretroviral Therapy N Engl J Med 2011; 365: 493-505.].

There has been conflicting information regarding the impact of ART use and sexual behaviour: some studies (particularly in resource rich countries) showing increased risk behaviour [12 Stolte IG, de Wit JB, van Eeden A, Coutinho RA, Dukers NH. Perceived viral load, but not actual HIV-1-RNA load, is associated with sexual risk behaviour among HIV-infected homosexual men AIDS 2004; 18: 1943-9.] while others showing a reduction in risk behaviour with ART [13 Bunnell R, Ekwaru JP, Solberg P, et al. Changes in sexual behavior and risk of HIV transmission after antiretroviral therapy and prevention interventions in rural Uganda AIDS 2006; 20: 85-92.-16 Kennedy C, O'Reilly K, Medley A, Sweat M. The impact of HIV treatment on risk behaviour in developing countries: a systematic review AIDS Care 2007; 19: 707-20.] . One study suggested that since ART availability there may be some evidence of increased risky behaviour in non-HIV infected people [17 Shafer LA, Nsubuga RN, White R, et al. Antiretroviral therapy and sexual behavior in Uganda: a cohort study AIDS 2011; 25: 671-8.]. Several studies have shown that the belief that having an undetectable viral load leads to lower infectiousness is associated with greater number of partners & less condom use[18 Kalichman SC, Cherry C, Amaral CM, et al. Adherence to antiretroviral therapy and HIV transmission risks: implications for test-and-treat approaches to HIV prevention AIDS Patient Care STDS 2010; 24: 271-7.-21 Crepaz N, Hart TA, Marks G. Highly active antiretroviral therapy and sexual risk behavior: a meta-analytic review JAMA 2004; 292: 224-36.] .

Many studies have shown a link between risky sexual behaviour and alcohol and substance abuse use in HIV positive and HIV negative people[22 Van Tieu H, Koblin BA. HIV, alcohol, and noninjection drug use Curr Opin HIV AIDS 2009; 4: 314-8.-25 Beckett M, Burnam A, Collins RL, Kanouse DE, Beckman R. Substance use and high-risk sex among people with HIV: a comparison across exposure groups AIDS Behav 2003; 7: 209-19.]. Some studies have suggested there is a link between poor adherence to ART and increased rates of unprotected sexual intercourse [26 Wilson TE, Barron Y, Cohen M, et al. Adherence to antiretroviral therapy and its association with sexual behavior in a national sample of women with human immunodeficiency virus Clin Infect Dis 2002; 34: 529-34., 27 Kalichman SC, Rompa D. HIV treatment adherence and unprotected sex practices in people receiving antiretroviral therapy Sex Transm Infect 2003; 79: 59-61.], but data from resource limited settings is limited. Poor adherence could be related to erratic lifestyle and health choices; condom use can also be affected by these factors so one could predict the other. Patients with worse adherence are more likely to have detectable VLs, if they then have unsafe sex they could potentially transmit drug-resistant HIV [28 Goldsamt LA, Clatts MC, Parker MM, Colon V, Hallack R, Messina MG. Prevalence of Sexually Acquired Antiretroviral Drug Resistance in a Community Sample of HIV-Positive Men Who Have Sex with Men in New York City AIDS Patient Care STDS 2011; 25: 287-93.]. A study in USA showed an association between poor adherence, perceived HIV viral load and increased number of sexual partners [18 Kalichman SC, Cherry C, Amaral CM, et al. Adherence to antiretroviral therapy and HIV transmission risks: implications for test-and-treat approaches to HIV prevention AIDS Patient Care STDS 2010; 24: 271-7.].

Few studies regarding adherence in Thailand have been reported; one showed good levels [29 Maneesriwongul WL, Tulathong S, Fennie KP, Williams AB. Adherence to antiretroviral medication among HIV-positive patients in Thailand J Acquir Immune Defic Syndr 2006; 43 Suppl1: S119-22.] but did not assess any correlation with unprotected sex risk. Our study aimed to assess the association in the levels of adherence in chronically infected Thai HIV positive people on stable ART and risky sexual behaviour which could lead to HIV transmission. It also explored use of alcohol, recreational drugs and patients’ beliefs regarding HIV transmission and whether these were related to having unprotected sex.

This cross sectional study had ethical approval in both Thailand and Australia. All patients attending a research clinic in Bangkok, who were either on an active clinical trial or on lifelong follow-up post clinical trial and taking ART for at least 6 months between August 2007 and November 2007, were invited to join the study. Participants were asked to fill out an anonymous, self administered questionnaire in Thai regarding their relationship details, ART adherence, sexual behaviour, alcohol and drug use[30 Mannheimer SB, Mukherjee R, Hirschhorn LR, et al. The CASE adherence index: A novel method for measuring adherence to antiretroviral therapy AIDS Care 2006; 18: 853-61.]. Adherence in the previous 30 days was assessed using a visual analogue scale (VAS) where patients indicated on a graduated line how often in the past month they took their ART from 0% (never took it) to 100% (did not miss a dose). Risk behaviours were assessed using questions adapted from validated questionnaires previously used in Thailand [31 Allen DR, Carey JW, Manopaiboon C, et al. Sexual health risks among young Thai women: implications for HIV/STD prevention and contraception AIDS Behav 2003; 7: 9-21.-33 Mansergh G, Naorat S, Jommaroeng R, et al. Inconsistent condom use with steady and casual partners and associated factors among sexually-active men who have sex with men in Bangkok, Thailand AIDS Behav 2006; 10: 743-51.]. This included questions regarding sexual activity in the last 30 days in terms of frequency, numbers/type of partners and condom use. Beliefs regarding HIV transmission were ascertained. A study team member accessed patient notes and computer results system for additional information about medical history and VL/CD4 results closest to date of questionnaire completion. Patients were defined as having unprotected sex risk (USR) if they had any unprotected sex with partners of negative or unknown HIV status in the last 30 days. Patients had no financial compensation for partaking in the study. This study is registered at www.clinicaltrial.gov number NCT00511056.

The adherence rates in our cohort were lower than expected with only 57% reporting adherence of ≥95% in the last 30 days on the visual analogue scale, but despite this the viral loads in our cohort were suppressed in the majority (96%) of patients. This finding agrees with other studies noting that the current more potent ART may be more forgiving than previously thought[3 Bangsberg DR. Less than 95% adherence to nonnucleoside reverse-transcriptase inhibitor therapy can lead to viral suppression Clin Infect Dis 2006; 43: 939-41.]. Unsurprisingly patients reporting a VAS <95% had a higher rates of viral loads >200copies/mL (OR 5.0). A small number of the patients with very low reported adherence (i.e. 5-45% on VAS) had undetectable viral loads so miscomprehension of the VAS instructions is a possible explanation although it has previously been well understood in a similar patient group[34 Kerr SJ, Avihingsanon A, Pucharoen O, et al. Assessing adherence in Thai patients taking HAART Int J STD AIDS 2012. (in press)]. Conversely some patients with excellent reported adherence had detectable VLs but may have been on failing regimes and waiting for regimen change or resistance results. Pill counts were not done to confirm reported adherence. Reasons for forgetting ART were in the majority practical issues of forgetting to bring the medications with them and travelling away from home. This could be potentially be remedied by providing easier more discreet packaging i.e. small pill boxes that can be kept in a pocket/bag at all times.

More than half (58%) of the patients were sexually active in the last 30 days and in the majority (80%) a condom was always used; this rate of condom use is higher than found in cohorts in Kenya (72%) and Uganda (66%) [35 Ragnarsson A, Ekstrom AM, Carter J, et al. Sexual risk taking among patients on antiretroviral therapy in an urban informal settlement in Kenya: a cross-sectional survey J Int AIDS Soc 2011; 14: 20., 36 Wagner GJ, Holloway I, Ghosh-Dastidar B, Ryan G, Kityo C, Mugyenyi P. Factors associated with condom use among HIV clients in stable relationships with partners at varying risk for HIV in Uganda AIDS Behav 2010; 14: 1055-65.]. In those 56(19%) who did not always use a condom, more than half had a known HIV positive partner. The risk of an HIV positive person potentially passing on or acquiring another HIV virus appears to be minimal and the larger concern in this small group of seroconcordent couples would be acquiring sexually transmitted diseases and for females of becoming pregnant[37 Ssemwanga D, Lyagoba F, Ndembi N, et al. Multiple HIV-1 infections with evidence of recombination in heterosexual partnerships in a low risk Rural Clinical Cohort in Uganda Virology 2011; 411: 113-31., 38 Smith DM, Richman DD, Little SJ. HIV superinfection J Infect Dis 2005; 192: 438-4.]. Indeed, trying to conceive was a reason for non condom use in nearly 7%. Information on type of sex was not collected but each type is known to have different risks [39 Vittinghoff E, Douglas J, Judson F, McKirnan D, MacQueen K, Buchbinder SP. Per-contact risk of human immunodeficiency virus transmission between male sexual partners Am J Epidemiol 1999; 150: 306-11., 40 Gray RH, Wawer MJ, Brookmeyer R, et al. Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1- discordant couples in Rakai, Uganda Lancet 2001; 357: 1149-53.]. Interestingly nearly 28% of patients reported the lack of availability and/or lack of planning as a reason for non condom use. Condoms are given out for free to all patients in the HIV clinic so it is more likely that the lack of planning for sexual activity was the cause and patients need to be encouraged to carry condoms on them to be prepared.

Only 27 out of 512 (5%) were classified as USR (having had any unprotected sexual intercourse with a partner of negative or unknown HIV status in the last 30days). This is reassuringly low. The adherence in this group of patients was lower (46 vs 57%) than non-USR patients but this was not statistically significant and indeed despite this all USR patients had VL <50copies/mL . No information on sexually transmitted diseases was available but a previous study of 824 HIV positive asymptomatic patients in Bangkok showed Chlamydia trachomatis rates of 9.7% and Neisseria gonorrhoeae of 1.3%, with a high disease burden in sex workers and in younger patients; it is likely our cohort would have lower rates than this with an older median age (39years) and no sex workers [41 Srifeungfung S, Roongpisuthipong A, Asavapiriyanont S, et al. Prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae in HIV-seropositive patients and gonococcal antimicrobial susceptibility: an update in Thailand Jpn J Infect Dis 2009; 62: 467-70.]. Genital HIV RNA levels were not collected and the true potential infectivity of this small but important group of patients in this cohort is unknown but likely to be very small. Contrary to expectations there was no association of USR and poor adherence in this group. This association may not have been found due to small patient numbers exhibiting USR but may indicate that the unprotected sex was not due to ‘erratic’ lifestyles but rather due to other sex-related factors such as condom issues and HIV disclosure concerns. Indeed 40% reported their partner’s dislike of condoms as the reason for unprotected sexual intercourse. This exemplifies the complex nature of sexual risks including the importance of condom negotiation skills, particularly for women (who made up 67% of USR). Female gender was the only factor associated with increased risk of USR (OR 2.9). Ragnarsson et al., recently reported a similar finding in a cohort in Kenya with female gender having an OR of 3.03 for inconsistent condom use [35 Ragnarsson A, Ekstrom AM, Carter J, et al. Sexual risk taking among patients on antiretroviral therapy in an urban informal settlement in Kenya: a cross-sectional survey J Int AIDS Soc 2011; 14: 20.]. This group suggested possible reasons for their finding being a lack of individual negotiating power in intimate relationships and also reproductive desires; in our study none of the USR women reported reproductive desire as their reason for non condom use so difficulty with condom negotiation or partner choice are likely factors in our cohort and further work needs to be done e.g. acceptability testing of other barrier methods such as the female condom and teaching condom negotiation techniques.

In the questions regarding beliefs only 26% patients thought that taking ART would reduce transmission of HIV yet even fewer patients believed that having an undetectable viral load would affect HIV transmission. This study was carried out when there was less evidence regarding ART and HIV transmission, also many of the patients in the cohort have low incomes and may not have access to the latest HIV news e.g. through the internet and networks, to guide their decision making in unprotected sex risk. Medical staff discussing latest scientific information regarding transmission with patients need to clearly state the evidence so far and carefully tailor their advice to a patient’s individual situation to ensure partners are not inadvertently put at risk.

Only a small proportion of patients reported recreational drug use and over 2/3 did not drink alcohol; this implies that this cohort is not a high ‘risk taking’ group, either because of self selection by being someone willing to enter into a clinical trial or due to the regular counselling and advice given regarding risk behaviours, or likely a combination of both these factors. Of those who drank alcohol around the time of sex 22% did not subsequently use a condom and this supports findings of many other studies showing alcohol intake can lead to subsequent unsafe sexual practises[23 Woolf SE, Maisto SA. Alcohol use and risk of HIV infection among men who have sex with men AIDS Behav 2009; 13: 757-82., 24 Mansergh G, Flores S, Koblin B, Hudson S, McKirnan D, Colfax GN. Alcohol and drug use in the context of anal sex and other factors associated with sexually transmitted infections: results from a multi-city study of high-risk men who have sex with men in the USA Sex Transm Infect 2008; 84: 509-11.].

Limitations of this study include the fact that this was performed in a research setting so results may not be transferable to the general population where less intense medical input and counselling related to sexual risk and adherence may occur. Patients were only asked about sexual activity in the last 30 days which may have underestimated true sexual activity and hence risk behaviour in the cohort. The number of MSM in the cohort was low reflecting the epidemic of HIV in Thailand being largely heterosexual.

In summary unprotected sex risk was uncommon (27/512, 5%) and poor ART adherence was not associated with USR in this resource limited cohort. Women were significantly more likely to have USR and more work needs to be done to help women in condom negotiation particularly in serodiscordant relationships. HIV prevention strategies need to be focused on high transmission risk groups to be maximally effective (i.e. patients not on ART, seroconverting patients, undiagnosed patients) and this outpatient clinic cohort appears to have a reassuring low, although not negligible, risk of transmission.