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Abstract
This case report describes the case of an HIV-positive individual who had long-term virological suppression on antiretroviral therapy, who manifested HIV drug resistance during a syphilis-induced HIV viral load increase. This highlights how the acquisition of a sexually transmitted infection can have important ramifications for HIV suppression and potential HIV transmission to sexual partners.
- Antiretroviral therapy
- HIV
- resistance
- syphilis
- therapy
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Whereas antiretroviral therapy (ART) has dramatically reduced AIDS-related morbidity and mortality,1 the absence of HIV eradication with these drugs requires their lifelong use, making long-term toxicity and quality of life issues critical in the management of HIV-infected patients. The development of drug-resistant mutations on ART limits future drug treatment options and can result in increased pill burden and drug toxicities.
The onset of the development of resistance is suggested by a rise in HIV RNA; however, the significance of transient low level viraemia is still not completely understood.2 Proposed mechanisms include intra and intertest variability, random biological and statistical variations around a mean viral load below the lower limit of test detection, and fluctuation in the release of virus from latent T cells in sanctuary sites such as the gastrointestinal tract, as might occur during a concomitant sexually transmissible infection (STI).3 While the optimal management of transient viraemia is not established, the development or demonstration of drug resistance in this setting appears uncommon particularly in the presence of viral genotype directed ART.4
Case
A 39-year-old HIV-infected white homosexual man presented with a 2-week history of sore throat and fever. He had been diagnosed HIV-1 positive 18 years previously and was receiving tenofovir/emtricitabine fixed dose combination and nevirapine 400 mg once a day. A recent CD4 cell count was 517×106 cells/ml3 and HIV RNA was less than 40 copies/ml. He reported unprotected insertive and receptive oral sex with two casual male partners during the preceding 3 months.
Examination revealed pharyngitis and a solitary left tonsillar ulcer.
Blood results revealed a positive Treponema pallidum enzyme immunoassay, T pallidum particle agglutination assay and a rapid plasma reagin (RPR) titre of 1:8. The syphilis serology had been negative 1 year previously. A diagnosis of infectious syphilis was made and intramuscular benzathine penicillin 2.4 megaunits treatment was given.
Coinciding with the rise in RPR, the HIV viral load rose from less than 40 copies/ml to 102 and subsequently 1144 copies/ml 2 weeks later despite excellent drug adherence. As shown in figure 1, this was the first detectable viral load since commencing highly active antiretroviral therapy (HAART) in 2000. Since 2000 treatment changes occurred solely in response to drug toxicity or new data. An HIV resistance genotype performed on the highest viral load of 1144 copies/ml showed the presence of the mutations M184I and G190A in the reverse transcriptase gene and G73S in the protease gene. There were no previous viral genotypes available. After 4 weeks the RPR had fallen to a neat titre, and the HIV viral load to less than 40 copies/ml. Despite resumed virological suppression, given the genetic fragility of nevirapine and the presence of potential resistance to his nucleos(t)ide backbone, nevirapine was changed to ritonavir-boosted darunavir.
Treatment history and HIV viral load. AZT, zidovudine; CBV, combivir; ddI, didanosine; DRV, darunavir; FTC, emtricitabine; NVP, nevirapine, RIT, ritonavir; TDF, tenofovir; VL, viral load.
Discussion
The case report raises two important points. First, that drug resistance-associated mutations can be present in a fully suppressive HAART regimen. Whether the resistant virus had always been present and was released from latent T cells activated during the immune response to infectious syphilis or developed upon viral rebound caused by the acquisition of syphilis is unknown.5 Nonetheless, it reinforces the low threshold investigating for HIV drug resistance during episodes of transient viraemia.
Second, it reminds clinicians and patients that virological suppression on ART can be affected by incident STI and as such it may be possible to transmit (drug-resistant) virus during such periods. Although semen viral load testing was not performed, plasma and semen viral load do correlate to a certain extent with one another and semen viral load is higher in the presence of concomitant STI.6 This reinforces the need for regular STI screens and viral genotypes to be performed in those with no baseline genotype who subsequently develop transient breakthrough viral replication. Co-infection with infectious syphilis, in particular, is associated with a rise in plasma HIV viral load by 0.22 RNA log10 copies/ml.3 The mechanism of this increase is unknown, but is likely to represent upregulated immune activation in the host, thus enhancing HIV replication.7–10
Poor adherence cannot categorically be excluded as a cause of the viral increase. However, the individual had a 10-year history of excellent adherence to HAART evidenced by full and sustained virological suppression, an adherence assessment identified no missed doses and the breakthrough viral replication coincided with syphilis acquisition making this an unlikely factor. Finally, our conclusions assume adequate performance of the viral load assay.
This case highlights the need to inform HIV-infected individuals who have an undetectable HIV viral load that the acquisition of a STI will increase their HIV infectiousness.
Key messages
Infectious syphilis is an important cause of transient viral replication.
Drug-resistant virus may be detectable during these events.
The process of immune activation may cause the release of potentially resistant HIV virus from latent reservoirs.
References
Footnotes
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.
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