Surveillance Of HIV Transmitted Drug Resistance In Latin America ...

Caribbean

Information on HIV TDR in the Caribbean is still very limited. Published data include 7 surveys: 4 from Cuba, 1 from the Dominican Republic, and 2 from Jamaica, all of them in mixed population (Table 3).

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Table 3. Publications on HIV PDR in the Caribbean, 2000–2015.

https://doi.org/10.1371/journal.pone.0158560.t003

In Cuba, moderate TDR prevalence to NRTIs (7.4%) was reported in a small survey performed in 1999 in 27 ARV-naïve subjects as part of a multi-country UNAIDS HIVDR study [24]. Nevertheless, a second survey performed in Havana in 2003 in 250 ARV naïve individuals showed low prevalence of NRTI TDR, and no evidence of TDR to NNRTIs and PIs [25]. This study was later expanded to 401 participants, including samples from 2007–2011 observing a significant increase in TDR in recently infected individuals compared to 2003 (14.8 vs. 3.8%; OR 3.9, 95% CI 1.5–17.0, p = 0.02). This increase was mostly due to NRTI TDR [26]. Additionally, a survey including 200 patients enrolled between 2009 and 2011 reported an overall TDR prevalence of 21.5%, with K103N and M184V being the most frequent TDR mutations [27]. In all, these results suggest a significant increase in TDR in Cuba, mainly due to NRTI TDR, reaching high or borderline high levels in the most recent surveys.

Data from a more recent HIVDR survey performed in Santo Domingo, Dominican Republic, in 2007–2010 in 103 ART-naïve adults enrolled in a prospective observational cohort study, showed moderate TDR to any ARV class (7.8%), 6.8% TDR to NNRTIs and 1.0% to NRTI [28].

A recent survey in Kingston, Jamaica, including 79 amplifiable samples reported a moderate overall TDR level (10.1%) [29]. This work contrasts with an older study reporting high (29%) overall TDR levels in Jamaica [30] and a recent small study reporting high level TDR in pregnant women attending antenatal clinics in Kingston [31].

After performing a meta-analysis from 9 studies [2 additional studies focused on HIV diversity in ART-naïve individuals with available sequences were included: [32, 33]], encompassing 1,004 individuals, the global TDR observed in the Caribbean for the whole study period was 8.5% (95% CI: 6.8–10.4; Table 2). The most prevalent DR mutations included M41L (1.1%), M184V (2.0%) for NRTI, and K103N (2.2%), Y181C (1.4%) and G190A (1.2%) for NNRTI (Fig 4).

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Fig 4. Drug resistance mutation frequency comparison, 2000–2005 vs. 2006–2015, for the Caribbean.

Drug resistance mutation frequency is shown for the studies included in the meta-analysis. Only surveillance mutations included in the WHO list are shown, ordered by drug family. *Significant differences (p<0.05), Fisher’s exact test. NRTI–nucleoside reverse transcriptase inhibitors; NNRTI–non-nucleoside reverse transcriptase inhibitors; PI–protease inhibitors.

https://doi.org/10.1371/journal.pone.0158560.g004

Of note, an important and significant increase in TDR was observed in the region, when comparing 2000–2005 with 2006–2015 (p<0.0001; Table 2) or 2000–2005 with 2011–2015 (p = 0.02; S1 Table), with a significant increase in TDR to all drug classes (Table 2). This increase in TDR was also associated with significant increase in the prevalence of several DR mutations, mainly M184V for NRTI; and K103N, Y181C and G190A for NNRTI. Remarkably, PI TDR was not observed during 2000–2005, appearing later in the 2006–2015 period, when PI DR mutations were observed at low frequencies in the population (Table 2, Fig 4).