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IntroductionGlobal HIV infections due to HIV-1 recombinants are increasing and impede prevention and treatment efforts. Key populations suffer most new HIV infections, but their role in the spread of HIV-1 recombinants is unknown. We conducted a global analysis of the associations between key populations and HIV-1 recombinants.MethodsWe searched PubMed, EMBASE, CINAHL, and Global Health for HIV-1 subtyping studies published from 1/1/1990 to 31/12/2015. Unpublished data was collected through a global survey. We included studies with HIV-1 subtyping data of key populations collected during 1990-2015. Key populations assessed were heterosexual people (HET), men who have sex with men (MSM), people who inject drugs (PWID), vertical transmissions (VERT), commercial sex workers (CSW), and transfusion-associated infections (BLOOD). Logistic regression was used to determine associations of key populations with HIV-1 recombinants. Subgroup analyses were performed for circulating recombinant forms (CRFs), unique recombinant forms (URFs), regions, and time periods.ResultsEight hundred and eighty five datasets including 77,284 participants from 83 countries were included. Globally, PWID were associated with the greatest odds of recombinants and CRFs (OR 2.6 [95% CI 2.46–2.74] and 2.99 [2.83–3.16]), compared to HET. CSW were associated with increased odds of recombinants and URFs (1.59 [1.44–1.75] and 3.61 [3.15–4.13]). VERT and BLOOD were associated with decreased odds of recombinants (0.58 [0.54–0.63] and 0.43 [0.33–0.56]). MSM were associated with increased odds of recombinants in 2010–2015 (1.43 [1.35–1.51]). Subgroup analyses supported our main findings.DiscussionAs PWID, CSW, and MSM are associated with HIV-1 recombinants, increased preventative measures and HIV-1 molecular surveillance are crucial within these key populations.Systematic review registrationPROSPERO [CRD42017067164].

Global HIV-1 genetic diversity forms a major obstacle to the development of an HIV vaccine. It may be necessary to employ subtype-specific HIV-1 vaccines in individual countries according to their HIV-1 subtype distribution. We estimated the global and regional need for subtype-specific HIV-1 vaccines. We took into account the proportions of different HIV-1 variants circulating in each country, the genetic composition of HIV-1 recombinants, and the different genome segments (gag, pol, env) that may be incorporated into vaccines. We modeled different scenarios according to whether countries would employ subtype-specific HIV-1 vaccines against (1) the most common subtype; (2) subtypes contributing more than 5% of HIV infections; or (3) all circulating subtypes. For therapeutic vaccines targeting the most common HIV-1 subtype in each country, 16.5 million doses of subtype C vaccine were estimated globally, followed by subtypes A (14.3 million) and B (4.2 million). A vaccine based on env required 2.6 million subtype E doses, and a vaccine based on pol required 4.8 million subtype G doses. For prophylactic vaccines targeting the most common HIV-1 subtype in each country, 1.9 billion doses of subtype A vaccine were estimated globally, followed by subtype C (1.1 billion) and subtype B (1.0 billion). A vaccine based on env required 1.2 billion subtype E doses, and a vaccine based on pol required 0.3 billion subtype G doses. If subtype-specific HIV-1 vaccines are also directed against less common subtypes in each country, vaccines targeting subtypes D, F, H, and K are also needed and would require up to five times more vaccine doses in total. We conclude that to provide global coverage, subtype-specific HIV-1 vaccines need to be directed against subtypes A, B, and C. Vaccines targeting env also need to include subtype E and those targeting pol need to include subtype G.

In Haiti, >90% of the population descended from African slaves. Of 7,147 Haitian pregnant women sampled, 44% of hepatitis B virus (HBV) infections were caused by genotype A1, which today is found mainly in eastern Africa. Twenty percent belong to a rare subgenotype, A5, which has been found only in the former Bight of Benin, a former primary slave trading post. Haitian A subgenotypes appear to have separated early from the African subgenotypes; the most prevalent genotype and subgenotype in West Africa today (E and A3, respectively) are rare in Haiti. This difference indicates that the dominant subgenotypes in Africa emerged in the general population only after the slave trade and explains the low genetic diversity of genotype E. The high prevalence of HBV genotype E in much of Africa further suggests that HBV hyperendemicity is a recent phenomenon, probably resulting from extensive use of unsafe needles.

The molecular epidemiology of HIV-1 in the Caribbean has been described using partial genome sequencing; subtype B is the most common subtype in multiple countries. To expand our knowledge of this, nearly full genome amplification, sequencing and analysis was conducted.Virion RNA from sera collected in Haiti, Dominican Republic, Jamaica and Trinidad and Tobago were reverse transcribed, PCR amplified, sequenced and phylogenetically analyzed. Nearly full genomes were completed for 15 strains; partial pol was done for 67 strains. All but one of the 67 strains analyzed in pol were subtype B; the exception was a unique recombinant of subtypes B and C collected in the Dominican Republic. Of the nearly full genomes of 14 strains that were subtype B in pol, all were subtype B from one end of the genome to the other and not inter-subtype recombinants. Surprisingly, the Caribbean subtype B strains clustered significantly with each other and separate from subtype B from other parts of the pandemic.The more complete analysis of HIV-1 from 4 Caribbean countries confirms previous research using partial genome analysis that the predominant subtype in circulation was subtype B. The Caribbean strains are phylogenetically distinct from other subtype B strains although the biological meaning of this finding is unclear.

Since 1999 GHESKIO, a large voluntary counseling and HIV testing center in Port-au-Prince, Haiti, has had an ongoing collaboration with the Haitian Ministry of Health to reduce the rate of mother to child HIV transmission. There are limited data on the ability to administer complex regimens for reducing mother to child transmission and on risk factors for continued transmission and infant mortality within programmatic settings in developing countries.We analyzed data from 551 infants born to HIV-infected mothers seen at GHESKIO, between 1999 and 2005. HIV-infected mothers and their infants were given "short-course" monotherapy with antiretrovirals for prophylaxis; and, since 2003, highly active antiretroviral therapy (HAART) when clinical or laboratory indications were met. Infected women seen in the pre-treatment era had 27% transmission rates, falling to 10% in this cohort of 551 infants, and to only 1.9% in infants of women on HAART. Mortality rate after HAART introduction (0.12 per year of follow-up [0.08-0.16]) was significantly lower than the period before the availability of such therapy (0.23 [0.16-0.30], P

New rapid syphilis tests permit simple and immediate diagnosis and treatment at a single clinic visit. We compared the cost-effectiveness, projected health outcomes, and annual cost of screening pregnant women using a rapid syphilis test as part of scaled-up prenatal testing to prevent mother-to-child HIV transmission in Haiti.A decision analytic model simulated health outcomes and costs separately for pregnant women in rural and urban areas. We compared syphilis syndromic surveillance (rural standard of care), rapid plasma reagin test with results and treatment at 1-wk follow-up (urban standard of care), and a new rapid test with immediate results and treatment. Test performance data were from a World Health Organization-Special Programme for Research and Training in Tropical Diseases field trial conducted at the GHESKIO Center Groupe Haitien d'Etude du Sarcome de Kaposi et des Infections Opportunistes in Port-au-Prince. Health outcomes were projected using historical data on prenatal syphilis treatment efficacy and included disability-adjusted life years (DALYs) of newborns, congenital syphilis cases, neonatal deaths, and stillbirths. Cost-effectiveness ratios are in US dollars/DALY from a societal perspective; annual costs are in US dollars from a payer perspective. Rapid testing with immediate treatment has a cost-effectiveness ratio of $6.83/DALY in rural settings and $9.95/DALY in urban settings. Results are sensitive to regional syphilis prevalence, rapid test sensitivity, and the return rate for follow-up visits. Integrating rapid syphilis testing into a scaled-up national HIV testing and prenatal care program would prevent 1,125 congenital syphilis cases and 1,223 stillbirths or neonatal deaths annually at a cost of $525,000.In Haiti, integrating a new rapid syphilis test into prenatal care and HIV testing would prevent congenital syphilis cases and stillbirths, and is cost-effective. A similar approach may be beneficial in other resource-poor countries that are scaling up prenatal HIV testing.