First Line Treatment Response in Patients with Transmitted HIV Drug Resistance and Well Defined Time Point of HIV Infection: Updated Results from the German HIV-1 Seroconverter Study

Background: Transmission of drug-resistant HIV-1 (TDR) can impair the virologic response to antiretroviral combination therapy. Aim of the study was to assess the impact of TDR on treatment success of resistance test-guided first-line therapy in the German HIV-1 Seroconverter Cohort for patients infected with HIV between 1996 and 2010. An update of the prevalence of TDR and trend over time was performed. Methods: Data of 1,667 HIV-infected individuals who seroconverted between 1996 and 2010 were analysed. The WHO drug resistance mutations list was used to identify resistance-associated HIV mutations in drug-naïve patients for epidemiological analysis. For treatment success analysis the Stanford algorithm was used to classify a subset of 323 drug-naïve genotyped patients who received a first-line cART into three resistance groups: patients without TDR, patients with TDR and fully active cART and patients with TDR and non-fully active cART. The frequency of virologic failure 5 to 12 months after treatment initiation was determined. Results: Prevalence of TDR was stable at a high mean level of 11.9% (198/1,667) in the HIV-1 Seroconverter Cohort without significant trend over time. Nucleotide reverse transcriptase inhibitor resistance was predominant (6.0%) and decreased significantly over time (OR = 0.92, CI = 0.87–0.98, p = 0.01). Non-nucleoside reverse transcriptase inhibitor (2.4%; OR = 1.00, CI = 0.92–1.09, p = 0.96) and protease inhibitor resistance (2.0%; OR = 0.94, CI = 0.861.03, p = 0.17) remained stable. Virologic failure was observed in 6.5% of patients with TDR receiving fully active cART, 5,6% of patients with TDR receiving non-fully active cART and 3.2% of patients without TDR. The difference between the three groups was not significant (p = 0.41). Conclusion: Overall prevalence of TDR remained stable at a rather high level. No significant differences in the frequency of virologic failure were identified during first-line cART between patients with TDR and fully-active cART, patients with TDR and non-fully active cART and patients without TDR

High Prevalence and High Incidence of Coinfection with Hepatitis B, Hepatitis C, and Syphilis and Low Rate of Effective Vaccination against Hepatitis B in HIV-Positive Men Who Have Sex with Men with Known Date of HIV Seroconversion in Germany

Objectives: Men who have sex with men (MSM) are at higher risk for coinfection with hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis than the general population. HIV infection and these coinfections accelerate disease progression reciprocally. This study evaluated the prevalence and incidence of these coinfections in HIV1-positive MSM in Germany. Materials and Methods: As part of a nationwide, multicenter, prospective cohort study of HIV-infected MSM, plasma samples collected yearly were screened for HBsAg and antibodies to HBc, HBs, HCV, and syphilis. Samples with indications of active HBV or HCV infection were confirmed by polymerase chain reaction. Prevalence and incidence of each infection and incidence rates per study participant were calculated, and incidences over 4-year time intervals compared. Results: This study screened 5,445 samples from 1,843 MSM. Median age at HIV seroconversion was 33 years. Prevalences of active, cleared, and occult HBV, and of active/cleared HCV were 1.7%, 27.1%, 0.2%, and 8.2%, respectively, and 47.5% had been effectively vaccinated against HBV. Prevalence of antibodies to Treponema pallidum and of triple or quadruple sexually transmitted infections (STIs) were 39.6% and 18.9%, respectively. Prevalence of STI, cleared HBV, HBV vaccination, and history of syphilis differed significantly among age groups. Incidences of HBV, HCV, and syphilis were 2.51, 1.54, and 4.06 per 100 person-years, respectively. Incidences of HCV and syphilis increased over time. HCV incidence was significantly higher in MSM coinfected with syphilis and living in Berlin, and syphilis incidence was significantly higher for MSM living in Berlin. Discussion: Despite extensive HBV vaccination campaigns, fewer than 50% of screened MSM were effectively vaccinated, with a high proportion of HIV-positive MSM coinfected with HBV. High rates of STI coinfections in HIV-positive MSM and increasing incidences emphasize the need for better tailored campaigns for HBV vaccination and STI prevention

Flow chart of patient groups.

<p>Flow chart of patient groups.</p

Composition of first-line cART 1996–2010.

<p>Composition of first-line cART 1996–2010.</p

Characteristics of patients included in treatment success analysis<b>.</b>

<p>^a sc: seroconversion.</p><p>¹ chi-square test.</p><p>² Kruskal-wallis test.</p><p>³ HR: hazard ratio.</p><p>° MSM: men who have sex with men.</p><p>∧ TDR: transmitted drug resistance according to Stanford algorithm.</p><p>* IQR: interquartile range.</p><p>“ CI: 95% confidence interval.</p><p>∼ cc: cell count.</p>×<p>VL: Viral load.</p> = <p>FL-ART: first-line AR.</p

Characteristics of study population.

<p>^asc: seroconversion.</p><p>¹Fisher exact test.</p><p>²Mann-Whitney-U test.</p><p>³Log rank test.</p><p>°MSM: men who have sex with men].</p><p>*IQR: Interquartile range.</p><p>"CI: 95% confidence interval.</p>∼<p>cc: cell count.</p>×<p>FL-ART: first-line cART.</p

Prescribing practices of NRTIs, NNRTIs and PIs in first-line treatment*.

<p>∧TDR: transmitted drug resistance according to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0095956#pone.0095956-Bennett1" target="_blank">[42]</a>.</p><p>*Drugs listed also if administered in combined pills.</p