Deciphering the Complex Distribution of Human Immunodeficiency Virus Type 1 Subtypes among Different Cohorts in Northern Tanzania.

Increased understanding of the genetic diversity of HIV-1 is challenging but important in the development of an effective vaccine. We aimed to describe the distribution of HIV-1 subtypes in northern Tanzania among women enrolled in studies preparing for HIV-1 prevention trials (hospitality facility-worker cohorts), and among men and women in an open cohort demographic surveillance system (Kisesa cohort). The polymerase encompassing partial reverse transcriptase was sequenced and phylogenetic analysis performed and subtype determined. Questionnaires documented demographic data. We examined factors associated with subtype using multinomial logistic regression, adjusted for study, age, and sex. Among 140 individuals (125 women and 15 men), subtype A1 predominated (54, 39%), followed by C (46, 33%), D (25, 18%) and unique recombinant forms (URFs) (15, 11%). There was weak evidence to suggest different subtype frequencies by study (for example, 18% URFs in the Kisesa cohort versus 5-9% in the hospitality facility-worker cohorts; adjusted relative-risk ratio (aRR) = 2.35 [95% CI 0.59,9.32]; global p = 0.09). Compared to men, women were less likely to have subtype D versus A (aRR = 0.12 [95% CI 0.02,0.76]; global p = 0.05). There was a trend to suggest lower relative risk of subtype D compared to A with older age (aRR = 0.44 [95% CI 0.23,0.85] per 10 years; global p = 0.05). We observed multiple subtypes, confirming the complex genetic diversity of HIV-1 strains circulating in northern Tanzania, and found some differences between cohorts and by age and sex. This has important implications for vaccine design and development, providing opportunity to determine vaccine efficacy in diverse HIV-1 strains

Deciphering the Complex Distribution of Human Immunodeficiency Virus Type 1 Subtypes among Different Cohorts in Northern Tanzania

Background: Increased understanding of the genetic diversity of HIV-1 is challenging but important in the development of an effective vaccine. We aimed to describe the distribution of HIV-1 subtypes in northern Tanzania among women enrolled in studies preparing for HIV-1 prevention trials (hospitality facility-worker cohorts), and among men and women in an open cohort demographic surveillance system (Kisesa cohort). Methods: The polymerase encompassing partial reverse transcriptase was sequenced and phylogenetic analysis performed and subtype determined. Questionnaires documented demographic data. We examined factors associated with subtype using multinomial logistic regression, adjusted for study, age, and sex. Results: Among 140 individuals (125 women and 15 men), subtype A1 predominated (54, 39%), followed by C (46, 33%), D (25, 18%) and unique recombinant forms (URFs) (15, 11%). There was weak evidence to suggest different subtype frequencies by study (for example, 18 % URFs in the Kisesa cohort versus 5–9 % in the hospitality facility-worker cohorts; adjusted relative-risk ratio (aRR) = 2.35 [95 % CI 0.59,9.32]; global p = 0.09). Compared to men, women were less likely to have subtype D versus A (aRR = 0.12 [95 % CI 0.02,0.76]; global p = 0.05). There was a trend to suggest lower relative risk of subtype D compared to A with older age (aRR = 0.44 [95 % CI 0.23,0.85] per 10 years; global p = 0.05). Conclusions: We observed multiple subtypes, confirming the complex genetic diversity of HIV-1 strains circulating i

Study-, age- and sex-adjusted associations between subtype and participant characteristics.

<p>[1] P-value from likelihood ratio test, relative to model with study, age and sex only.</p><p>[2] HIV seroconverters defined as those with ≤36 months between last negative and first positive test dates.</p><p>[3] Including food preparation, <i>mamalishe</i> and bar work.</p><p>[4] Only 33% of men reported the number of lifetime partners, so it was not possible to fit a model with both sex and number of lifetime partners, therefore the results reported are study- and age-adjusted only (and compared to model with study and age only).</p><p>[5] Imputed as half the lower limit of detection (300 copies/ml, except the 10 subsequent seroconverters, where the lower limit of detection was 75 copies/ml), for those with undetectable HIV VL.</p

pol gene analysis tree.

<p>Results are presented for the 136 sequences which passed for phylogenetic analysis.</p

Participant characteristics by cohort.

<p>%) for categorical variables and median [interquartile range] for continuous variables. Percentages are of non-missing values. Results are n (</p><p>[1] HIV seroconverters defined as those with ≤36 months between last negative and first positive test dates.</p><p>[2] P-value omitted since differences are by design.</p><p>[3]Including food preparation, <i>mamalishe</i> and bar work.</p><p>[4] Lower limit of detection was 300 copies/ml, except for the 10 subsequent seroconverters, where the lower limit of detection was 75 copies/ml.</p><p>[5] Imputed as half the lower limit of detection, for those with undetectable HIV VL.</p><p>[6] Comparing categories split by the overall median.</p

Map of the study areas in northern Tanzania.

<p>Created using StatSilk (2013; StatPlanet: Interactive Data Visualization and Mapping Software. <a href="http://www.statsilk.com" target="_blank">http://www.statsilk.com</a>).</p

Subtypes by participant characteristics.

<p>Results are n (%) for categorical variables and median [interquartile range] for continuous variables. Percentages are of non-missing values. URF = unique recombinant form.</p><p>[1] P-value from Χ² test.</p><p>[2] HIV seroconverters defined as those with ≤36 months between known last negative and first positive test dates.</p><p>[3] Including food preparation, <i>mamalishe</i> and bar work.</p><p>[4] Imputed as half the lower limit of detection (300 copies/ml, except for the 10 subsequent seroconverters, where the lower limit of detection was 75 copies/ml), for those with undetectable HIV VL. Median is as shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081848#pone-0081848-t001" target="_blank">Table 1</a> (4.5 log₁₀ copies/ml).</p