Building laboratory capacity to support HIV care in Nigeria: Harvard/APIN PEPFAR, 2004-2012.

Introduction: From 2004-2012, the Harvard/AIDS Prevention Initiative in Nigeria, funded through the US President's Emergency Plan for AIDS Relief programme, scaled up HIV care and treatment services in Nigeria. We describe the methodologies and collaborative processes developed to improve laboratory capacity significantly in a resource-limited setting. These methods were implemented at 35 clinic and laboratory locations.

Association of Bacterial vaginosis and other Sexually Transmitted Infections with HIV among pregnant women in Nigeria.

Objectives: To determine the association of Bacterial vaginosis (BV) and other sexually transmissible infections (STIs) with HIV prevalence among pregnant women in Jos, Nigeria.

Methods: This was a cross- sectional study of pregnant women who participated in the Prevention of Mother-to-Child Transmission of HIV program of the AIDS Prevention Initiative in Nigeria, between April 2002 and July 2004, at the Jos University Teaching Hospital in Jos, Nigeria. Blood, high vaginal and endocervical samples were obtained for diagnosis of HIV, BV and other STIs.

Short communication: Transmitted HIV drug resistance in antiretroviral-naive pregnant women in north central Nigeria.

The World Health Organization (WHO) recommends periodic surveillance of transmitted drug resistance (TDR) in communities in which antiretroviral therapy (ART) has been scaled-up for greater than 3 years. We conducted a survey of TDR mutations among newly detected HIV-infected antiretroviral (ARV)-naive pregnant women. From May 2010 to March 2012, 38 ARV-naive pregnant women were recruited in three hospitals in Jos, Plateau state, north central Nigeria.

Impact of hepatitis C virus on HIV response to antiretroviral therapy in Nigeria.

The effect of hepatitis C virus (HCV) on antiretroviral therapy (ART) response in patients in sub-Saharan Africa is unknown. We studied 1431 HIV-infected ART initiators in Jos, Nigeria, of whom 6% were HCV coinfected. A similar proportion of HIV/HCV-coinfected and HIV-monoinfected patients achieved HIV RNA <400 copies per milliliter after 24 and 48 weeks of ART (P > 0.

Immunologic criteria are poor predictors of virologic outcome: implications for HIV treatment monitoring in resource-limited settings.

Background: Viral load (VL) quantification is considered essential for determining antiretroviral treatment (ART) success in resource-rich countries. However, it is not widely available in resource-limited settings where the burden of human immunodeficiency virus infection is greatest. In the absence of VL monitoring, switches to second-line ART are based on World Health Organization (WHO) clinical or immunologic failure criteria.

NeuroAIDS in Africa.

In July 2009, the Center for Mental Health Research on AIDS at the National Institute of Mental Health organized and supported the meeting "NeuroAIDS in Africa." This meeting was held in Cape Town, South Africa, and was affiliated with the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. Presentations began with an overview of the epidemiology of HIV in sub-Saharan Africa, the molecular epidemiology of HIV, HIV-associated neurocognitive disorders (HANDs), and HAND treatment.

Impact of hepatitis B virus infection on human immunodeficiency virus response to antiretroviral therapy in Nigeria.

Background: As highly active antiretroviral therapy (ART) is introduced into areas of the world in which hepatitis B virus (HBV) infection is highly endemic, it is important to determine the influence of HBV on persons with human immunodeficiency virus (HIV) and HBV coinfection who are receiving ART.

Methods: We studied 1564 HIV-infected patients in Jos, Nigeria, who initiated ART. Participants with HIV-HBV coinfection had hepatitis B e antigen (HBeAg) and HBV DNA status determined.

The level of APOBEC3G (hA3G)-related G-to-A mutations does not correlate with viral load in HIV type 1-infected individuals.

The APOBEC family of mammalian cytidine deaminases, such as APOBEC3G (hA3G), has been demonstrated to function as a host viral restriction factor against HIV-1. hA3G has been shown to cause extensive G-to-A mutations in the HIV-1 genome, which may play a role in viral restriction. To investigate the role of G-to-A mutations in HIV-1 pathogenesis, we isolated, amplified, and sequenced HIV-1 sequences (vif, gag, and env) from 29 therapy-naive HIV-1-infected individuals.

Interplay of reverse transcriptase inhibitor therapy and gag p6 diversity in HIV type 1 subtype G and CRF02_AG.

Abstract The gag p6 region of HIV-1 has various nonsubstitutionary mutations, including insertions, duplications, deletions, and premature stop codons. Studies have linked gag p6 mutations to reduced susceptibility to antiretroviral therapy in HIV-1 subtype B. This study examined the relationship between antiretroviral therapy and gag p6 diversity in HIV-1 CRF02_AG and subtype G.

Relationship between human immunodeficiency type 1 infection and expression of human APOBEC3G and APOBEC3F.

Background: Human immunodeficiency virus type 1 (HIV-1)-infected individuals with a high viral set point progress to acquired immunodeficiency syndrome (AIDS) more rapidly than those with a low viral set point. It is not entirely clear which host and viral factors are responsible for the viral set point. Host factors that affect virus replication are likely to influence the viral set point.

Characterization of HIV type 1 reverse transcriptase mutations in infants infected by mothers who received peripartum nevirapine prophylaxis in Jos, Nigeria.

This study was carried out to characterize HIV-1 reverse transcriptase (RT) mutations in vertically infected infants in Jos, Nigeria. DNA was extracted from peripheral blood mononuclear cells of 102 infants, aged 0 to 6 months, born to HIV-1-infected mothers who had received peripartum single-dose nevirapine prophylaxis. PCR-based diagnosis revealed that 14 infants (13.

Twenty years of prospective molecular epidemiology in Senegal: changes in HIV diversity.

Over a 20-year period we have observed the dynamics of HIV-1 subtypes and HIV-2 infection in a prospective cohort of registered female sex workers (FSW) in Dakar, Senegal. Prevalence and incidence rates for HIV-1 and HIV-2 are described from 290 seroprevalent and 193 seroincident subjects who were among the 3,910 women enrolled between 1985 and 2004. We report a significant decrease of HIV-2 prevalence in the cohort, parallel to the introduction and rise of HIV-1 infection.

The complexity of circulating HIV type 1 strains in Oyo state, Nigeria.

Multiple HIV-1 subtypes and circulating recombinant forms (CRFs) are known to circulate in West Africa. We undertook a survey of HIVs in Oyo state, in southwestern Nigeria. We analyzed 71 samples from Ibadan, the capital city, and 33 samples from Saki, 100 miles west of Ibadan.

Direct evidence of lower viral replication rates in vivo in human immunodeficiency virus type 2 (HIV-2) infection than in HIV-1 infection.

Studies have shown that human immunodeficiency virus type 2 (HIV-2) is less pathogenic than HIV-1, with a lower rate of disease progression. Similarly, plasma viral loads are lower in HIV-2 infection, suggesting that HIV-2 replication is restricted in vivo in comparison to that of HIV-1. However, to date, in vivo studies characterizing replication intermediates in the viral life cycle of HIV-2 have been limited.

Long-term intrapatient viral evolution during HIV-2 infection.

Background. Disease progression and transmission of human immunodeficiency virus (HIV) type 2 are attenuated, compared with HIV-1, which is consistent with the lower plasma viral loads observed in HIV-2 infection. Although numerous studies have characterized the intrapatient evolution of viral sequences during HIV-1 infection, prospective studies examining intrapatient evolution during HIV-2 infection have been limited.

Subtype-specific patterns in HIV Type 1 reverse transcriptase and protease in Oyo State, Nigeria: implications for drug resistance and host response.

As the use of antiretroviral therapy becomes more widespread across Africa, it is imperative to characterize baseline molecular variability and subtype-specific peculiarities of drug targets in non-subtype B HIV-1 infection. We sequenced and analyzed 35 reverse transcriptase (RT) and 43 protease (PR) sequences from 50 therapy-naive HIV-1-infected Nigerians. Phylogenetic analyses of RT revealed that the predominant viruses were CRF02_AG (57%), subtype G (26%), and CRF06_cpx (11%).

Genomic sites of human immunodeficiency virus type 2 (HIV-2) integration: similarities to HIV-1 in vitro and possible differences in vivo.

Retroviruses have distinct preferences in integration site selection in the host cell genome during in vitro infection, with human immunodeficiency virus type 1 (HIV-1) integration strongly favoring transcriptional units. Additionally, studies with HIV-1 have shown that the genomic site of proviral integration may impact viral replication, with integration in heterochromatin associated with a block in viral transcription. HIV-2 is less pathogenic than HIV-1 and is believed to have a lower replication rate in vivo.

Characterization of complete HIV type 1 genomes from non-B subtype infections in U.S. military personnel.

Infections with non-B HIV-1 subtypes are rare in the United States, but comprise a significant percentage of infections among U.S. military personnel.

Viral dynamics of primary HIV-1 infection in Senegal, West Africa.

Background: Few studies have addressed primary human immunodeficiency virus (HIV) type 1 infection in sub-Saharan Africa, where the epidemic is of a predominantly heterosexual character and is caused by different subtypes. The present study examines the dynamics of viral replication in subjects infected with various HIV-1 subtypes.

Methods: Seven hundred fifty-two HIV-negative Senegalese women at high risk for infection were monitored every 3 months for acute/early HIV infection; 26 infections were identified (23 HIV-1 and 3 HIV-2), with an HIV-1 incidence rate of 3.

Comparison of a new, affordable flow cytometric method and the manual magnetic bead technique for CD4 T-lymphocyte counting in a northern Nigerian setting.

We compared two techniques for CD4 T-lymphocyte counting: flow cytometry (Cyflow) and magnetic beads (Dynabead). Similar results with good correlation were obtained from the 40 adult blood samples counted (P=0.057, r=0.

Molecular epidemiology of human immunodeficiency virus type 1 sub-subtype A3 in Senegal from 1988 to 2001.

The global human immunodeficiency virus (HIV)epidemic is characterized by significant genetic diversity in circulating viruses. We have recently characterized a group of viruses that form a distinct sub-subtype within the subtype A radiation, which we have designated HIV type 1 (HIV-1) sub-subtype A, circulating in West Africa. A prospective study of a cohort of female sex workers (FSW) in Dakar, Senegal over an 18-year period indicated that an A3-specific sequence in the C2-V3 region of the env gene was found in 46 HIV-1-infected women.

Distinct human immunodeficiency virus type 1 subtype A virus circulating in West Africa: sub-subtype A3.

Phylogenetic analyses demonstrate significant diversity in worldwide circulating strains of human immunodeficiency virus type 1 (HIV-1). Detailed studies have revealed a complex pattern of intersubtype recombinations, as well as evidence of sub-subtypes circulating in various populations. In this study, we characterized an HIV-1 strain that had previously been identified as a distinct subcluster within the subtype A radiation based on partial sequence data.

Highly active antiretroviral therapy and viral response in HIV type 2 infection.

Human immunodeficiency virus type 2 (HIV-2), the second human retrovirus known to cause AIDS, is endemic to West Africa but is infrequently found outside this region. We present a case series of 10 HIV-2--infected individuals treated in the United States. Physicians applied the principles of highly active antiretroviral therapy (HAART), normally used in treating HIV type 1, with modifications considered appropriate for treating HIV-2.

A high-density admixture map for disease gene discovery in african americans.

Admixture mapping (also known as "mapping by admixture linkage disequilibrium," or MALD) provides a way of localizing genes that cause disease, in admixed ethnic groups such as African Americans, with approximately 100 times fewer markers than are required for whole-genome haplotype scans. However, it has not been possible to perform powerful scans with admixture mapping because the method requires a dense map of validated markers known to have large frequency differences between Europeans and Africans. To create such a map, we screened through databases containing approximately 450000 single-nucleotide polymorphisms (SNPs) for which frequencies had been estimated in African and European population samples.

Regulation of adiponectin in human immunodeficiency virus-infected patients: relationship to body composition and metabolic indices.

HIV-related lipodystrophy is characterized by adipose redistribution, dyslipidemia, and insulin resistance. Adiponectin is an adipose-derived peptide thought to act as a systemic regulator of glucose and lipid metabolism. We investigated adiponectin concentrations in 10 HIV-infected patients during acute HIV infection (viral load, 2.