The number of individuals actively receiving HAART in BC increased from 837 to 5413 (+547%; p = 0.002) and the number of individuals newly testing positive for HIV per year declined from 702 to 338 cases from 1996 to 2009 (−52 %; p = 0.001). The overall correlation between the number of individuals actively receiving HAART and the number of individuals newly testing positive for HIV per year in BC from 1996 to 2009 was −0.89 (p<0.001). As shown in , HAART usage and new HIV diagnoses per year showed three distinct phases during the study period. Between 1996 and 1999, we retrospectively observed a steep increase in the number of individuals on HAART (+258%; p=0.021), which reflects the initial roll out of HAART in the province, resulting from the 1996 IAS-USA guidelines. During this period, new HIV diagnoses per year decreased sharply (−40%; p=0.003). Between 2000 and 2003, HAART use increased slightly (+9%; p<0.001), due to the relative balance between treatment interruptions and HAART initiations (new and returning patients). During this period, new HIV diagnoses per year also remained relatively stable (+5%; p=0.954). Between 2004 and 2009, we prospectively observed a second slower but steady increase in the number of individuals on HAART (+51%; p<0.001), based on the emerging 2004 IAS-USA guidelines56, which recommended against structured treatment interruptions. During this third period, new HIV diagnoses per year decreased substantially (−23%; p<0.001). When the data were stratified by prior history of injection drug use, there was a ~50% decline in annual new diagnoses among individuals with prior history of injection drug use, from 159 cases in 1999 to 80 cases in 2009 (p = 0.003). In contrast, the number of new positive tests remained stable (p-value 0.6229) among individuals with no history of injection drug use.
Figure 1 a. Number of active highly active antiretroviral therapy (HAART) participants in the British Columbia Centre for Excellence in HIV/AIDS and number of New HIV-positive diagnoses per year in British Columbia from 1996 to 2009. p refers to the p-value for (more ...)
Next, we estimated the number of new HIV diagnoses that would have been expected at steady state in each of the three periods under investigation (1996–2000, 2001–2003, and 2004–2009). We compared the actual number of new HIV diagnoses in a particular year to the number that would have been expected if the rate of new HIV diagnoses remained constant over the same period. For each period, the number of observed new HIV diagnoses was divided by expected new HIV diagnoses, to determine whether there was an increase or decrease in the number of new HIV diagnoses. As shown in , for 1996–2000, we determined that there were 30 % (Rate ratio [RR]: 0.70; 95% CI: 0.67 – 0.72) fewer new HIV diagnoses than expected. For 2001–2003, we showed that the number of observed and expected new HIV diagnoses were essentially the same – a decrease of 1.7% (RR: 0.98; 95% CI: 0.93 – 1.04). In the last period, 2004–2009, we observed a decline in new HIV diagnoses of 16.6% (RR: 0.83; 95% CI: 0.80 – 0.87).
shows yearly distribution of pre-HAART CD4 cell counts from 1996 until 2009, as a surrogate for the timing of HAART initiation. Substantial differences are apparent between the three study phases: pre-HAART CD4 cell counts were highest in 1996-99 (peak in 1997 – median 310 cells/mm3); lowest in 2000-03 (nadir in 2003 – median 150 cells/mm3); and steadily increasing in 2004-09 (peak in 2009 – median 270 cells/mm3). The trends in CD4 count at baseline (pre-HAART) were tested in each one of the study periods using Cochran-Armitage Trend Test for the proportion of CD4 <200/mm3. We found that the baseline CD4 cell count decreased (p = 0.024) in the 1996 – 1999 period, and decreased again in the 2000 – 2003 period (p < 0.001), but it increased significantly (p < 0.001) in the 2004 – 2009 period.
Distribution of annual pre-HAART CD4 cell count (cells/mm3) for all individuals initiating HAART in British Columbia from 1996 until 2009. Median yearly baseline CD4 cell counts are listed below the horizontal axis and illustrated (X) on the plot.
To further explore the contribution of HIV viral load to the trends in the number of new HIV diagnoses in BC, we characterized the viral load per year in the province, stratified by prior history of injection drug use between 1996 and 2009. As shown in , the number of individuals with viral load < 500 c/mL, regardless of history of injection drug use, increased dramatically during the study period, starting from <10% in 1996 to over 50% in 2009 (p < 0.001). Additionally, between 2004 and 2009, the proportion of patients with no prior history of injection drug use with viral load below 500 and 50 copies/mL increased by 36% (p<0.001) and 42% (p=0.001), respectively. In contrast, the same proportion among patients with prior history of injection drug use increased by 82% (p=0.001) and 86% (p=0.002), respectively. Secondarily, from the Poisson regression modeling the association of new HIV positive tests, viral load, year and number of individuals on HAART, we estimated that for a 100 increase in the number of individuals on HAART, the estimated number of new HIV cases decreased by a factor of 0.97 (95% confidence interval 0.96–0.98), and per 1 log10 decrease in viral load, the estimated number of new HIV cases decreased by a factor of 0.86 (95% confidence interval 0.75–0.98).
Distribution of the highest HIV-1 RNA plasma level for all individuals in British Columbia who ever had a HIV-1 RNA levels in plasma test from 1996 until 2009.
We considered whether the decreased number of new HIV diagnoses could result from decreased HIV testing during periods of increased HAART use, but found that the total number of HIV tests performed in the province had actually increased steadily over the study period. The average number of HIV tests performed was 137,585/year between 1996 and 1999 (or an average of 3.5% of the BC population), 139,464/year between 2000 and 2003 (or an average of 3.4% of the BC population) and 168,924/year between 2004 and 2008 (or an average of 4.0% of the BC population). Also of note, the rates of infectious syphilis, genital gonorrhea and genital chlamydia increased steadily during 1996–2008.30
For infectious syphilis, the crude rate per 100,000 population increased from 0.5 in 1996 to 7.4 in 2008; for genital gonorrhea, the crude rate per 100,000 population increased from 12.6 in 1996 to 31.3 in 2008; and for genital chlamydia, the crude rate per 100,000 population increased from 106.2 in 1996 to 239.3 in 2008. The rate of hepatitis C decreased from 158.2 in 1996 to 87.0 in 2003 (−45% decrease; p<0.001) and to 55.8 per 100,000 population in 2008 (36% decrease from 2003; p<0.001).