Perceived viral load, but not actual HIV-1-RNA load, is associated with sexual risk behaviour among HIV-infected homosexual men
AIDS: Volume 18(14), 24 September 2004
Stolte, Ineke Ga; de Wit, John BFb; van Eeden, Arnec; Coutinho, Roel Aa,d; Dukers, Nicole HTMa
From the aCluster of Infectious Diseases, HIV and STI Research, Municipal Health Service Amsterdam, Amsterdam, the Netherlands; bDepartment of Social and Organizational Psychology, University of Utrecht, Utrecht, the Netherlands; cJan van Goyen Clinic, Amsterdam, the Netherlands; and dDepartment of Human Retrovirology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Increases in sexual risk behaviour and sexually transmitted infections among HIV-infected homosexual men after the introduction of highly active antiretroviral therapy (HAART) confirm the need for innovative prevention activities. The present study focused on time trends in sexual risk behaviour and predictors for unprotected anal intercourse in the HAART era among HIV-infected homosexual men.
In 2000-2003, 57 HIV-infected homosexual men (mean age 45 years) were interviewed in three serial data waves. Logistic regression, correcting for repeated measurements, was used to assess time trends in risky sex, and the association between HAART-related beliefs, and both the perceived and actual viral load level and CD4 cell counts and subsequent risky sex.
Risky sex with casual partners increased from 10.5% in 2000 to 27.8% in 2003 (P < 0.01), and with steady partners of negative or unknown HIV status from 5.3% to 10.7% (P = 0.6).
Homosexual men with a favourable perception of their viral load were more likely to engage in subsequent risky sex with steady partners of negative or unknown HIV status than men with a less favourable perception of their viral load; this association was independent of the actual HIV-1-RNA load and CD4 cell counts.
Among those having unprotected anal intercourse with a steady partner of negative or unknown HIV status, all but one man perceived their viral load as very favourable, yet three (30%) had a detectable HIV-1-RNA load (> 2.6 HIV-1-RNA log copies/ml), varying from 2.68 to 4.23 log copies/ml. Among men reporting no risk behaviour with steady partners, there was a lower percentage (18.9%) perceiving their viral load as very favourable, when actually it was detectable.
The authors concluded that risky sex increased in this group of HIV-infected homosexual men. The perceived viral load, but not the actual load, is associated with subsequent risky sex with steady partners of negative or unknown HIV status. Care givers should discuss with patients not only their actual viral load and CD4 cell count but also their perceived viral load.
The introduction of highly active antiretroviral therapy (HAART) completely changed the prognosis of HIV-infected individuals in developed countries . Not unexpectedly, its increasing use coincided with increasing sexual risk behaviour and sexually transmitted infections (STI), notably syphilis and rectal gonorrhoea, among homosexual men, the major risk group for HIV in most developed countries [2-7]. A substantial proportion of the increase in syphilis infections is seen among HIV-infected homosexual men [6,8,9].
Several studies among both HIV-negative and HIV-infected homosexual men have found that optimistic beliefs as a result of the availability of HAART are associated with sexual risk behaviour [10-12]. Most of the studies were based on cross-sectional data. A longitudinal study among young HIV-negative homosexual men  found that especially perceiving less HIV/AIDS threat since the availability of HAART was associated with a change from protected to unprotected anal intercourse with casual partners.
For HIV-infected individuals, treatment with HAART and their immunological and virological status were likewise associated with increased levels of STI and sexual risk behaviour in some studies [14-17], but not in others [3,15,18,19]. As studies involved different groups, and geographical regions, different phases after the introduction of HAART, and with different HAART-related variables of interest, results are difficult to compare.
To our knowledge HAART-related optimism and actual immunological and virological status have not been investigated together in relation to sexual risk behaviour. This is important as it might provide useful information for preventing further increases in STI or the renewed spread of HIV infections among homosexual men. We therefore examined time trends in such behaviour with casual partners and steady partners of negative or unknown HIV status, and prospectively investigated the relationship between HAART-related beliefs, perceived and actual viral load and CD4 cell counts, and sexual risk behaviour.
Design and data collection
The Amsterdam Cohort Studies (ACS) among homosexual men started in 1984. Participants who were HIV positive at entry or seroconverted during follow-up were followed at the Municipal Health Service until January 1999, when their clinical follow-up was transferred to the Jan van Goyen HIV treatment clinic in Amsterdam. Behavioural follow-up of HIV-infected homosexual men stopped in 1997. To gain insight into the recent sexual behaviour of HIV-infected ACS participants, three waves of data collection were conducted from January 2000 until May 2003 among those who were regularly seen at the HIV treatment clinic. Questionnaires were sent by mail, to be returned voluntarily and without charge. Men not responding to the first questionnaire or refusing further participation were not approached for subsequent waves.
The questionnaires gathered information about individual sexual behaviour, HAART treatment, perceptions about personal viral load and CD4 cell counts, and HAART-related beliefs. Information on actual HIV-1-RNA load, and CD4 cell counts was available from the clinical follow-up.
Analyses of HIV-1 antibodies were performed using two commercially available enzyme-linked immunosorbent assays (Abbot Laboratories, North Chicago, IL, USA; Vironostika, Organon Teknika, Boxtel, the Netherlands) and confirmed by Western blot analyses. Analyses of CD4 cell counts were performed prospectively by cytofluorometry. Until 2000, HIV-1-RNA loads were determined using the NucliSens test (Organon Teknika), with a quantification threshold of 400 HIV-1-RNA copies/ml. Thereafter, use shifted to the more sensitive branched DNA test (Organon Teknika), with a quantification threshold of 50 HIV-1-RNA copies/ml. After July 1996, HIV-1-RNA testing was prospective, and results (including whether the HIV-1-RNA level is below or above the detection threshold) were available within one month after testing.
During the first data wave (January-April 2000), 176 questionnaires were sent, and 141 men (80%) responded. Of the 128 men who received a questionnaire in the second wave (November 2001-February 2002), 105 men (82%) responded. During the final wave (January-April 2003), 107 questionnaires were sent and 64 men (60%) responded. Of the men that were lost to follow-up, six died, 20 withdrew participation; for the remainder the reason for drop-out is unknown.
For present study, only men who returned all three questionnaires (N = 57) were included in the analyses. They accounted for 171 visits, the median age in the first data wave was 43 years [interquartile range (IQR) 37.8-53.6], the median time since HIV-positive ACS entry or seroconversion was 4.7 years (IQR 3.0-9.9). Most men were of Dutch nationality (80.7%) and used HAART in the 6 months preceding the first data wave (78.9%). The median time on HAART in the first data wave was 2.8 years (minimum 1.3, maximum 4.2). All characteristics were comparable between the men who returned one or two questionnaires and those (N = 57) who returned all three, except for the item of unprotected anal intercourse with casual partners. The 57 men reported less of such intercourse in the past 6 months than did those who were lost to follow-up, indicating that men who dropped out were a higher risk group.
Participants were asked whether they had engaged in insertive or receptive anal intercourse in the past 6 months and whether they used condoms during anal intercourse. Risk behaviour was defined as not always having used condoms during anal intercourse. It was defined separately for casual partners and for steady partners of negative or unknown HIV status. Participants reporting no anal intercourse or the consistent use of condoms during anal intercourse were considered not to be at risk.
Beliefs and perceptions
The questionnaires included nine items measuring HAART-related beliefs, to which participants responded using a seven-point scale ranging from 1 'strongly disagree' to 7 'strongly agree'. A higher score represented a stronger agreement with the beliefs. Items were clustered on the basis of principal component analyses, as in a previous study among HIV-negative homosexual men in Amsterdam. This approach resulted in three scales measuring types of HAART-related beliefs, which were confirmed by reliability analysis in the three data waves: perceiving less HIV/AIDS threat since HAART availability [two items, with a correlation (r) ranging from 0.62 to 0.75]; perceiving less infectiousness as a result of HAART (two items, r from 0.75 to 0.84), and perceiving less need for safe sex since HAART (two items, r from 0.47 to 0.75). Scores on the HAART-related beliefs were calculated as the mean scores of the two items included. Perceptions of personal viral load level and CD4 cell count, were both measured on a seven-point scale ranging from 1 'very unfavourable' to 7 'very favourable'.
Information on actual HIV-1-RNA levels and CD4 cell counts was available from clinical follow-up, allowing the evaluation of its effect on sexual risk behaviour. For analyses, individual HIV-1-RNA levels, as measured in the 3-12 months preceding the questionnaire, were transformed to log copies, and their arithmetic mean was used as a continuous predictor variable. Likewise, the mean of the individual CD4 cell counts measured over the 3-12 months was used as a continuous predictor variable. Finally, data also provided information on age, time since HIV-positive ACS entry or seroconversion, and self reported HAART use in the past 6 months.
Trends in risk behaviour
The number of men who reported unprotected sexual intercourse with casual partners in the previous 6 months increased from 6 (10.5%) in 2000 to 15 (27.8%) in 2003. This increase was statistically significant after correction for age, time since HIV-positive ACS entry or seroconversion, HAART treatment, actual HIV-1-RNA load and CD4 cell counts [odds ratio (OR) 2.08; 95% confidence interval (CI) 1.02-4.26]. Additional analyses revealed an increase in both insertive and receptive unsafe anal intercourse with casual partners, with unsafe insertive anal intercourse increasing more than unsafe receptive anal intercourse. The number of men who reported unprotected anal intercourse with steady partners of negative or unknown HIV status, in the previous 6 months, increased from three (5.3%) in 2000 to six (10.7%) in 2003. This trend was not statistically significant. When unsafe insertive and receptive anal intercourse with steady partners were separated, receptive anal intercourse remained stable, whereas unprotected insertive anal intercourse increased marginally significantly (P = 0.09).
Sexual risk behaviour and perceptions
During the first data wave, the median score on the variable perceiving less HIV/AIDS threat since HAART was 4.0 (IQR 3.0-5.5), indicating that most men were neutral. Most men did not perceive less need for safe sex (median 1.0, IQR 1.0-1.0) or less infectiousness as a result of HAART (median 1.0, IQR 1.0-2.0). In general, men perceived their viral load level and CD4 cell counts as very favourable (median 7.0 and 6.0, respectively). An undetectable ( 2.6 log copies) viral load level was seen in 61% of the men. The percentage of men with an undetectable viral load increased to 79% in the third data wave (χ2 for linear trend P = 0.05). In the 3-12 months preceding the first data wave, the mean HIV-1-RNA load was 2.82 log copies/ml (SD ± 0.51), and 83.5% of the men had a mean CD4 cell count greater than 350 × 108/l.
For unprotected anal intercourse with casual partners, no significant association between the variables under study and sexual risk behaviour could be identified. With steady partners of negative or unknown HIV status, however, unprotected anal intercourse was independently associated with a previous favourable perception of the viral load level. Men with a more favourable perception of their viral load were found to be more likely to engage in unprotected anal intercourse with steady partners in the subsequent data wave compared with men with a less favourable perception of their viral load. (OR 5.58; 95% CI 1.94-16.05). Forcing the actual HIV-1-RNA load and CD4 cell counts into the model revealed no changes, indicating that the association between perceived viral load and sexual risk was independent of the actual HIV-1-RNA level. Neither perceived nor actual CD4 cell counts were associated with risk behaviour.
This study, using longitudinal data, is among the first to investigate which specific aspects of HAART availability, varying from optimism to actual immunological and virological status, are predictive of sexual risk behaviour among HIV-infected homosexual men. Findings indicate that men's perceptions of their viral load levels, and not their actual HIV-1-RNA levels, are related to unprotected anal intercourse with steady partners of negative or unknown HIV status. Addressing these perceptions might help to prevent the ongoing homosexual transmission of STI and HIV.
Over 4 years the proportion of unprotected anal intercourse with casual partners increased in this group of older HIV-infected homosexual men, from 10.5% in 2000 to 27.8% in 2003. Unprotected anal intercourse with steady partners of negative or unknown HIV status showed a non-significant rising trend from 5.3 to 10.7%. These increases are in concordance with findings in other studies and coincide with an upsurge in syphilis infections, of which a substantial proportion is seen among HIV-infected homosexual men. Although we have no information about the serostatus of the casual partners, and men might choose their sexual partner based on concordant serostatus, the increase particularly in unprotected insertive anal intercourse is worrying, as the per-contact risk of HIV transmission to an HIV-negative partner is considerably higher than with unprotected receptive anal intercourse. If these trends represent more general trends, the STI epidemic will continue and might even result in a renewed spread of HIV among homosexual men.
To prevent HIV and other STI, possible predictors of risk behaviour in the HAART era must be recognized. In general, the HIV-infected homosexual men in this study were quite realistic about HIV/AIDS in the HAART era, but HIV-infected homosexual men appear somewhat more optimistic than HIV-negative men. This is in concordance with the fact that HIV-infected men in this study were more inclined to perceive less HIV/AIDS threat since HAART than HIV-negative young men we studied earlier.
To our knowledge, no other study has investigated the prospective association between HAART-related beliefs and sexual risk behaviour among HIV-infected homosexual men, while taking into account their actual HIV-1-RNA levels and CD4 cell counts. Results indicate that none of the predictors under study were associated with unsafe sex with casual partners. Interestingly, HIV-infected men who perceived their viral load as more favourable were more likely to report unprotected anal intercourse with steady partners of negative or unknown HIV status in the subsequent data wave. This association was found independently of the actual HIV-1-RNA level, which itself was not associated with unprotected anal intercourse with steady partners. This suggests that a man's actual HIV-1-RNA levels might not match his perceived viral load level. Additional analysis indeed found that the percentage of men who perceived their viral load as very favourable, even while having a detectable HIV-1-RNA level, is higher (30%) among men engaging in unprotected anal intercourse with steady partners of negative or unknown HIV status than among men who did not (18.9%). None of the other HAART-related beliefs were found to be associated with unsafe sex with steady partners.
As this study is among the first to investigate prospectively how unsafe sexual behaviour is affected by both optimistic beliefs as a result of HAART and by immunological and virological status, present and previous results are difficult to compare. Shortly after the introduction of HAART, a temporarily higher level of unprotected sex with casual partners was found among HIV-infected homosexual men in Amsterdam after HAART rendered their HIV-1-RNA levels undetectable and raised their CD4 cell counts . The fact that the present study fails to find such an association might confirm that these first virological and immunological improvements indeed have only a temporary effect on sexual risk behaviour. Alternatively, the effects of immunological and virological improvements after starting HAART on sexual behaviour might have changed over time, and most HIV-infected individuals now start HAART earlier in their infection. One study suggested that reductions in perceived infectiousness predict engaging in unprotected intercourse . Although the perceived viral load in our study must be interpreted carefully, it is plausible that men who perceive their viral load as very favourable indeed feel less infectious.
Study limitations include the relatively low numbers, thus we have to be cautious in interpreting the results. Lack of power could be the cause for finding no predictors for unprotected anal intercourse with casual partners, and larger studies are needed to confirm our results. Furthermore, care should be taken in generalizing these findings to the total population of HIV-infected homosexual men because of selection bias. Our study population consisted predominantly of older, highly educated men. Moreover, they probably represent a lower risk group, as men who were lost to follow-up and therefore were excluded from the analyses, reported higher levels of sexual risk-taking with casual partners in the first data wave. As the results might not be representative of all homosexual men in the Netherlands, or either of homosexual men internationally, further research is needed to confirm our results. This is important to acknowledge especially when results are being used for developing new prevention methods in various settings. The study nevertheless reveals interesting exploratory findings, which could be useful for prevention.
Unprotected anal intercourse with both casual and steady partners increased in this group of HIV-infected men. None of the predictors under study were associated with unsafe sex with casual partners, and further research is needed to identify other predictors. Importantly, a more favourable perception of the viral load level seems to predict subsequent unsafe anal intercourse with steady partners of negative or unknown HIV status. It is alarming that some men with a favourable perception of their viral load while actually having a detectable load engage in unsafe sex with steady partners who may be HIV negative, posing a high risk of HIV transmission. In addition to discussing the actual HIV-1-RNA levels and CD4 cell counts, care-givers should enquire into patients' perceptions of their viral load in relation to their sexual behaviour, and actively prevent 'false' perceptions. If findings in this study are representative of homosexual men in general, this idea could be incorporated into treatment and counselling strategies, and might help prevent the ongoing transmission of STI and even a possibly renewed spread of HIV among homosexual men.