Correction: Rare HIV-1 transmitted/founder lineages identified by deep viral sequencing contribute to rapid shifts in dominant quasispecies during acute and early infection.

[This corrects the article DOI: 10.1371/journal.ppat.1006510.].

Rare HIV-1 transmitted/founder lineages identified by deep viral sequencing contribute to rapid shifts in dominant quasispecies during acute and early infection.

In order to inform the rational design of HIV-1 preventive and cure interventions it is critical to understand the events occurring during acute HIV-1 infection (AHI). Using viral deep sequencing on six participants from the early capture acute infection RV217 cohort, we have studied HIV-1 evolution in plasma collected twice weekly during the first weeks following the advent of viremia. The analysis of infections established by multiple transmitted/founder (T/F) viruses revealed novel viral profiles that included: a) the low-level persistence of minor T/F variants, b) the rapid replacement of the major T/F by a minor T/F, and c) an initial expansion of the minor T/F followed by a quick collapse of the same minor T/F to low frequency. In most participants, cytotoxic T-lymphocyte (CTL) escape was first detected at the end of peak viremia downslope, proceeded at higher rates than previously measured in HIV-1 infection, and usually occurred through the exploration of multiple mutational pathways within an epitope. The rapid emergence of CTL escape variants suggests a strong and early CTL response. Minor T/F viral strains can contribute to rapid and varied profiles of HIV-1 quasispecies evolution during AHI. Overall, our results demonstrate that early, deep, and frequent sampling is needed to investigate viral/host interaction during AHI, which could help identify prerequisites for prevention and cure of HIV-1 infection.

Prospective Study of Acute HIV-1 Infection in Adults in East Africa and Thailand.

BACKGROUND: Acute human immunodeficiency virus type 1 (HIV-1) infection is a major contributor to transmission of HIV-1. An understanding of acute HIV-1 infection may be important in the development of treatment strategies to eradicate HIV-1 or achieve a functional cure. METHODS: We performed twice-weekly qualitative plasma HIV-1 RNA nucleic acid testing in 2276 volunteers who were at high risk for HIV-1 infection. For participants in whom acute HIV-1 infection was detected, clinical observations, quantitative measurements of plasma HIV-1 RNA levels (to assess viremia) and HIV antibodies, and results of immunophenotyping of lymphocytes were obtained twice weekly. RESULTS: Fifty of 112 volunteers with acute HIV-1 infection had two or more blood samples collected before HIV-1 antibodies were detected. The median peak viremia (6.7 log10 copies per milliliter) occurred 13 days after the first sample showed reactivity on nucleic acid testing. Reactivity on an enzyme immunoassay occurred at a median of 14 days. The nadir of viremia (4.3 log10 copies per milliliter) occurred at a median of 31 days and was nearly equivalent to the viral-load set point, the steady-state viremia that persists durably after resolution of acute viremia (median plasma HIV-1 RNA level, 4.4 log10 copies per milliliter). The peak viremia and downslope were correlated with the viral-load set point. Clinical manifestations of acute HIV-1 infection were most common just before and at the time of peak viremia. A median of one symptom of acute HIV-1 infection was recorded at a median of two study visits, and a median of one sign of acute HIV-1 infection was recorded at a median of three visits. CONCLUSIONS: The viral-load set point occurred at a median of 31 days after the first detection of plasma viremia and correlated with peak viremia. Few symptoms and signs were observed during acute HIV-1 infection, and they were most common before peak viremia. (Funded by the Department of Defense and the National Institute of Allergy and Infectious Diseases.).

Kericho CLinic-based ART Diagnostic Evaluation (CLADE): design, accrual, and baseline characteristics of a randomized controlled trial conducted in predominately rural, district-level, HIV clinics of Kenya.

BACKGROUND: Prospective clinical trial data regarding routine HIV-1 viral load (VL) monitoring of antiretroviral therapy (ART) in non-research clinics of Sub-Saharan Africa are needed for policy makers. METHODS: CLinic-based ART Diagnostic Evaluation (CLADE) is a randomized, controlled trial (RCT) evaluating feasibility, superiority, and cost-effectiveness of routine VL vs. standard of care (clinical and immunological) monitoring in adults initiating dual nucleoside reverse transcriptase inhibitor (NRTI)+non-NRTI ART. Participants were randomized (1:1) at 7 predominately rural, non-research, district-level clinics of western Kenya. Descriptive statistics present accrual patterns and baseline cohort characteristics. RESULTS: Over 15 months, 820 adults enrolled at 7 sites with 86-152 enrolled per site. Monthly site enrollment ranged from 2-92 participants. Full (100%) informed consent compliance was independently documented. Half (49.9%) had HIV diagnosed through voluntary counseling and testing. Study arms were similar: mostly females (57.6%) aged 37.6 (SD = 9.0) years with low CD4 (166 [SD = 106]) cells/m3). Notable proportions had WHO Stage III or IV disease (28.7%), BMI <18.5 kg/m2 (23.1%), and a history of tuberculosis (5.6%) or were receiving tuberculosis treatment (8.2%) at ART initiation. In the routine VL arm, 407/409 (99.5%) received baseline VL (234,577 SD = 151,055 copies/ml). All participants received lamivudine; 49.8% started zidovudine followed by 38.4% stavudine and 11.8% tenofovir; and, 64.4% received nevirapine as nNRTI (35.6% efavirenz). CONCLUSIONS: A RCT can be enrolled successfully in rural, non-research, resource limited, district-level clinics in western Kenya. Many adults presenting for ART have advanced HIV/AIDS, emphasizing the importance of universal HIV testing and linkage-to-care campaigns. TRIAL REGISTRATION: ClinicalTrials.gov NCT01791556.

Influence of culture on contraceptive utilization among HIV-positive women in Brazil, Kenya, and South Africa.

Contraceptive choice and discontinuation are poorly understood among HIV-positive women, and HIV disease and culture may influence decisions. We assessed factors influencing contraceptive decision-making among HIV-positive women in three countries. This qualitative assessment of 108 HIV-positive women (36/site, selected by age and parity strata) was conducted in Rio de Janeiro, Brazil; Kericho, Kenya; and Soweto, South Africa. Freelist interviews assessed knowledge and attitudes towards contraception and were analyzed enumerating frequency and saliency of mentions. There was intersite consensus around list items but priority and themes varied. Site-specific factors influencing contraceptive choice were male partner wishes and fertility desire (Brazil), side-effects (South Africa), and impact on health and HIV progression (Kenya). Age, parity, and taking antiretroviral therapy (ART) impacted some themes. Contraceptive use among HIV-positive women is substantially influenced by culture and other factors. Counseling efforts should consider individual factors in method selection and offer method variety to accommodate changing needs.

Factors influencing contraceptive choice and discontinuation among HIV-positive women in Kericho, Kenya.

This study explored perceptions towards and utilization of contraception among HIV-positive, reproduction-age women in Kericho, Kenya, an area with high HIV and low contraceptive prevalence rates. Qualitative methods were used in three focus group discussions and 15 in-depth interviews to gather data from 46 HIV-positive women ages 18 to 45, purposively selected by age strata. Analysis was performed using ATLAS-ti (ATLAS-ti Center, Berlin). Most participants reported familiarity with modern contraceptives. Participants generally perceived that men opposed contraception. Some women indicated that their HIV status dictated contraceptive decisions, particularly with regard to abstinence. Women reported method discontinuation because of side effects, having met desired parity, and menstrual changes. Findings suggested that perceptions about side effects, opinions of the male partner, and HIV disease progression play important roles in contraceptive decisions. Counseling can dispel incorrect information and optimize contraceptive practice in this setting.

Factors influencing contraceptive choice and discontinuation among HIV-positive women in Kericho, Kenya

This study explored perceptions towards and utilization of contraception among HIV-positive, reproduction-age women in Kericho, Kenya, an area with high HIV and low contraceptive prevalence rates. Qualitative methods were used in three focus group discussions and 15 in-depth interviews to gather data from 46 HIV-positive women ages 18 to 45, purposively selected by age strata. Analysis was performed using ATLAS-ti (ATLAS-ti Center, Berlin). Most participants reported familiarity with modern contraceptives. Participants generally perceived that men opposed contraception. Some women indicated that their HIV status dictated contraceptive decisions, particularly with regard to abstinence. Women reported method discontinuation because of side effects, having met desired parity, and menstrual changes. Findings suggested that perceptions about side effects, opinions of the male partner, and HIV disease progression play important roles in contraceptive decisions. Counseling can dispel incorrect information and optimize contraceptive practice in this setting (Afr J Reprod Health 2010; 14[4]: 103-114)

Immunogenetic correlates for Chlamydia trachomatis-associated tubal infertility.

OBJECTIVE: To understand immunogenetic mechanisms of Chlamydia trachomatis infection and tubal scarring. METHODS: We measured and compared previously significant human leukocyte antigen (HLA) class II DQ alleles, their linked DRB genes, and polymorphisms in selected cytokine genes (tumor necrosis factor alpha-308 promoter; transforming growth factor beta1-10 and -25 codons; interleukin 10-1082, -819, and -592 promoters; interleukin 6-174 promoter; and interferon gamma+874 codon 1) among Kenyan women with confirmed tubal infertility with and without C trachomatis microimmunofluorescence antibody. RESULTS: Two class II alleles, HLA-DR1*1503 and DRB5*0101, were detected less commonly in C trachomatis microimmunofluorescence seropositive women than in C trachomatis microimmunofluorescence seronegative women with infertility (0% versus 20%; odds ratio [OR] 0.05; 95% confidence interval [CI] 0, 0.7, and 6% versus 26%; OR 0.2; 95% CI 0.02, 1.0, respectively). These alleles are commonly linked as a haplotype at the DRB locus. This finding could not be explained through linkage disequilibrium with the other studied HLA or cytokine genes. CONCLUSION: These alleles may lead to an immunologically mediated mechanism of protection against C trachomatis infection and associated tubal damage, or alternatively increase risk for tubal scarring due to another cause.

Association between Mycoplasma genitalium and acute endometritis.

Up to 70% of cases of pelvic inflammatory disease do not have a known cause. We recruited 115 women who had presented to a clinic for sexually transmitted diseases in Nairobi, Kenya with pelvic pain that had persisted for 14 days or less, to look for an association between Mycoplasma genitalium and endometritis. With PCR, we detected M genitalium in the cervix, endometrium, or both in nine (16%) of 58 women with histologically confirmed endometritis and in one (2%) of 57 women without endometritis (p=0.02). Our results suggest that infection with M genitalium is strongly associated with acute endometritis in this population.