The role of recombination in the emergence of a complex and dynamic HIV epidemic

<p>Abstract</p> <p>Background</p> <p>Inter-subtype recombinants dominate the HIV epidemics in three geographical regions. To better understand the role of HIV recombinants in shaping the current HIV epidemic, we here present the results of a large-scale subtyping analysis of 9435 HIV-1 sequences that involve subtypes A, B, C, G, F and the epidemiologically important recombinants derived from three continents.</p> <p>Results</p> <p>The circulating recombinant form CRF02_AG, common in West Central Africa, appears to result from recombination events that occurred early in the divergence between subtypes A and G, followed by additional recent recombination events that contribute to the breakpoint pattern defining the current recombinant lineage. This finding also corrects a recent claim that G is a recombinant and a descendant of CRF02, which was suggested to be a pure subtype. The BC and BF recombinants in China and South America, respectively, are derived from recent recombination between contemporary parental lineages. Shared breakpoints in South America BF recombinants indicate that the HIV-1 epidemics in Argentina and Brazil are not independent. Therefore, the contemporary HIV-1 epidemic has recombinant lineages of both ancient and more recent origins.</p> <p>Conclusions</p> <p>Taken together, we show that these recombinant lineages, which are highly prevalent in the current HIV epidemic, are a mixture of ancient and recent recombination. The HIV pandemic is moving towards having increasing complexity and higher prevalence of recombinant forms, sometimes existing as "families" of related forms. We find that the classification of some CRF designations need to be revised as a consequence of (1) an estimated > 5% error in the original subtype assignments deposited in the Los Alamos sequence database; (2) an increasing number of CRFs are defined while they do not readily fit into groupings for molecular epidemiology and vaccine design; and (3) a dynamic HIV epidemic context.</p

Prevalence of complications of male circumcision in Anglophone Africa: a systematic review

BACKGROUND: There is growing evidence that male circumcision (MC) prevents heterosexual acquisition of HIV by males in sub-Saharan Africa, the region of the world heavily affected by the HIV pandemic. While there is growing support for wide-spread availability and accessibility of MC in Africa, there is limited discussion about the prevalence of physical complications of male circumcision on the continent. METHODS: A systematic literature search and review of articles in indexed journals and conference abstracts was conducted to collect and analyze prevalence of complications of MC in Anglophone sub-Saharan Africa. Information extracted included: indications for MC, complications reported, age of patients and category of circumcisers. RESULTS: There were 8 articles and 2 abstracts that were suitable for the analysis. The studies were not strictly comparable as some reported on a wide range of complications while others reported just a limited list of possible complications. Prevalence of reported complications of MC ranged from 0% to 50.1%. Excluding the study with 50.1%, which was on a series of haemophilia patients, the next highest prevalence of complications was 24.1%. Most of the complications were minor. There was no firm evidence to suggest that MCs performed by physician surgeons were associated with lower prevalence of complications when compared with non-physician health professionals. CONCLUSION: The available data are inadequate to obtain a reasonable assessment of the prevalence of complications of MC in sub-Saharan Africa. Some of the available studies however report potentially significant prevalence of complications, though of minor clinical significance. This should be considered as public health policy makers consider whether to scale-up MC as an HIV preventative measure. Decision for the scale-up will depend on a careful cost-benefit assessment of which physical complications are certainly an important aspect. There is need for standardized reporting of complications of male circumcision

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

HIV subtype is not associated with dementia among individuals with moderate and advanced immunosuppression in Kampala, Uganda

BACKGROUND: HIV-associated neurocognitive disorders (HAND) are a common neurological manifestation of HIV infection. A previous study suggested that HIV dementia may be more common among patients with subtype D virus than among those with subtype A virus among HIV+ individuals with advanced immunosuppression. We conducted a study to evaluate the frequency of HIV dementia, and the association of HIV dementia with HIV subtype and compartmentalization among HIV+ individuals with moderate and advanced immunosuppression (CD4 lymphocyte count >150 cells/μL and < 250 cells/μL). METHODS: The study enrolled 117 antiretroviral naïve HIV+ individuals in Kampala, Uganda. HIV+ individuals received neurological, neuropsychological testing, and functional assessments, and gag and gp41 regions were subtyped. Subjects were considered infected with a specific subtype if both regions analyzed were from the same subtype. RESULTS: 41% of the HIV+ individuals had HIV dementia (mean CD4 lymphocyte count= 233 cells/μL). 67 individuals had subtype A, 25 individuals had subtype D, 24 individuals were classified as A/D recombinants, and one individual had subtype C. There was no difference in the frequency of HIV dementia when stratified by HIV subtype A and D and no association with compartmentalization between the cerebrospinal fluid and peripheral blood. CONCLUSIONS: These results suggest that HIV dementia is common in HIV+ individuals in Uganda. There was no association between HIV subtype and dementia among HIV+ individuals with moderate and advanced immunosuppression. Future studies should be performed to confirm these results