National prevalence and trends of HIV transmitted drug resistance in Mexico

Abstract

Background: Transmitted drug resistance (TDR) remains an important concern for the management of HIV infection, especially in countries that have recently scaled-up antiretroviral treatment (ART) access.

Methodology/principal findings: We designed a study to assess HIV diversity and transmitted drug resistance (TDR) prevalence and trends in Mexico. 1655 ART-naïve patients from 12 Mexican states were enrolled from 2005 to 2010. TDR was assessed from plasma HIV pol sequences using Stanford scores and the WHO TDR surveillance mutation list. TDR prevalence fluctuations over back-projected dates of infection were tested. HIV subtype B was highly prevalent in Mexico (99.9%). TDR prevalence (Stanford score>15) in the country for the study period was 7.4% (95% CI, 6.2∶8.8) and 6.8% (95% CI, 5.7∶8.2) based on the WHO TDR surveillance mutation list. NRTI TDR was the highest (4.2%), followed by NNRTI (2.5%) and PI (1.7%) TDR. Increasing trends for NNRTI (p = 0.0456) and PI (p = 0.0061) major TDR mutations were observed at the national level. Clustering of viruses containing minor TDR mutations was observed with some apparent transmission pairs and geographical effects.

Conclusions: TDR prevalence in Mexico remains at the intermediate level and is slightly lower than that observed in industrialized countries. Whether regional variations in TDR trends are associated with differences in antiretroviral drug usage/ART efficacy or with local features of viral evolution remains to be further addressed.

Figure 1. Geographic distribution of individuals participating in the study.

1655 ART-naïve individuals from 12 Mexican states were enrolled in the current study. The percentage of individuals from each state participating in the study is shown in the cake slice to the left. The proportion of national HIV infections reported for each participating state according to data from the National Centre for HIV/AIDS Prevention and Control (CENSIDA) is shown in the cake slice to the right.

Figure 2. Antiretroviral drug (ARV) resistance levels to the most common antiretroviral drugs among individuals with transmitted drug resistance (TDR).

The levels of ARV drug resistance in the 122 of 1655 individuals with TDR in the Mexican cohort are shown. Low-level resistance corresponds to a Stanford Score (SS) between 15 and 29, intermediate-level resistance to a SS between 30 and 59, and high-level resistance to a SS equal to or over 60.

Figure 3. Transmitted drug resistance (TDR) trends in Mexico at the national level.

Approximate dates of infection were estimated using a model described by Mellors et al . TDR fluctuations were examined over the back-projected dates of infection by graphical methods using moving average with a six-month window. Significance was assessed with Poisson regression. Trends considering all TDR mutations and only major TDR mutations are shown.

Figure 4. Sub-trees for specific protease and RT TDR mutations.

Sub-trees were formed by selecting the patients that had a specific TDR mutation in one of the two genes, from the complete tree based on the other gene (see text for details). Zoom-ins on representative branches are shown on the right, expanding the information on the patients: State | Gender | date of sample collection | probable date of infection. Several branches (e.g. c and e) showed probable transmission pairs, while others formed small clusters with pairs within them (a and d). b and d show cases of widely circulating viruses with TDR mutations. Red lines show branches with boostrap values >90% for A71V and G333E, and blue lines for K103R. Lighter shades show bootstrap support >80%.