Survival probability and factors associated with time to loss to follow-up and mortality among patients on antiretroviral treatment in central Kenya.

BACKGROUND: Retention of patients who are receiving antiretroviral therapy (ART) remains a challenge especially in the setting of rapid expansion of HIV services. Retention in care remains vital to the HIV care continuum, and has been associated with viral suppression and improved survival. This study aimed to ascertain survival rates, time to loss to follow-up (LTFU) or mortality events and factors associated with time to LTFU or mortality among patients enrolled on antiretroviral therapy at health facilities in central Kenya. METHODS: This was a retrospective cohort study among patients initiated on ART between 2004 and 2012 in central Kenya. Demographic characteristics, clinical characteristics and outcomes data were analyzed using Stata version 15.1. Competing risks regression analysis and cummulative incidence functions were used to estimate survival. RESULTS: A total of 31,346 patients were included, of whom 65.6% were female, 76.0% were aged between 20 and 50 years old, and 38.9% were diagnosed at WHO stage III. At 36 months, overall retention was 68.8%, LTFU was 27.1%, and mortality was 4.1%. The total person-years of follow up was 74,986. The incidence rate of LTFU was 9.99 per 100 person years for a total of 9383.25 person-years of follow up. The mortality rate was 1.25 per 100 person years for a total of 875.5 person-years among those who died. The median time to LTFU was 11 months (IQR 3-22) while median time to death was 3 months (IQR 0-13). Men, unmarried patients, patients presenting with advanced HIV, not on TB treatment, and enrolled into the HIV program in later cohorts, had a shorter time to mortality and LTFU. CONCLUSION: Our study demonstrated evidence of scale-up of HIV treatment programs in central Kenya. While most patients were enrolled at an advanced WHO clinical stage, overall 36-month mortality remained low, but occurred earlier during follow-up. Cohort LTFU at 36-months reduced in later years with the losses occurring within the 1st year of follow-up. Predictors of early mortality and LTFU included being male, single, separated or divorced, advanced WHO clinical stage, and among patients not on TB treatment.

Trends in TB and HIV care and treatment cascade, Kenya, 2008-2018.

BACKGROUND: HIV infection is associated with high mortality among people with TB. Antiretroviral therapy (ART) reduces TB incidence and mortality among people living with HIV (PLHIV). Since 2005, Kenya has scaled up TB and HIV prevention, diagnosis and treatment. We evaluated the impact of these services on trends and TB treatment outcomes.METHODS: Using Microsoft Excel (2016) and Epi-Info 7, we analysed Kenya Ministry of Health TB surveillance data from 2008 to 2018 to determine trends in TB notifications, TB classification, HIV and ART status, and TB treatment outcomes.RESULTS: Among the 1,047,406 people reported with TB, 93% knew their HIV status, and 37% of these were HIV-positive. Among persons with TB and HIV, 69% received ART. Between 2008 and 2018, annual TB notifications declined from 110,252 to 96,562, and HIV-coinfection declined from 45% to 27%. HIV testing and ART uptake increased from 83% to 98% and from 30% to 97%, respectively. TB case fatality rose from 3.5% to 3.9% (P <0.018) among HIV-negative people and from 5.1% to 11.2% (P <0.001) among PLHIV on ART.CONCLUSION: TB notifications decreased in settings with suboptimal case detection. Although HIV-TB services were scaled-up, HIV-TB case fatality rose significantly. Concerted efforts are needed to address case detection and gaps in quality of TB care.

Can isoniazid preventive therapy be scaled up rapidly? Lessons learned in Kenya, 2014-2018.

BACKGROUND: TB is the leading cause of mortality among people living with HIV (PLHIV), for whom isoniazid preventive therapy (IPT) has a proven mortality benefit. Despite WHO recommendations, countries have been slow in scaling up IPT. This study describes processes, challenges, solutions, outcomes and lessons learned during IPT scale-up in Kenya.METHODS: We conducted a desk review and analyzed aggregated Ministry of Health (MOH) IPT enrollment data from 2014 to 2018 to determine trends and impact of program activities. We further analyzed IPT completion reports for patients initiated from 2015 to 2017 in 745 MOH sites in Nairobi, Central, Eastern and Western Kenya.RESULTS: IPT was scaled up 75-fold from 2014 to 2018: the number of PLHIV covered increased from 9,981 to 749,890. The highest percentage increases in the cumulative number of PLHIV on IPT were seen in the quarters following IPT pilot projects in 2014 (49%), national launch in 2015 (54%), and HIV treatment acceleration in 2016 (158%). Among 250,069 patients initiating IPT from 2015 to 2017, 97.5% completed treatment, 0.2% died, 0.8% were lost to follow-up, 1.0% were not evaluated, and 0.6% discontinued treatment.CONCLUSIONS: IPT can be scaled up rapidly and effectively among PLHIV. Deliberate MOH efforts, strong leadership, service delivery integration, continuous mentorship, stakeholder involvement, and accountability are critical to program success.

HLA class I associations with rates of HIV-1 seroconversion and disease progression in the Pumwani Sex Worker Cohort.

Class I human leukocyte antigens (HLA) play an important role in the adaptive immune response by presenting antigens to CD8+ T cells. Studies have reported that several HLA class I alleles are associated with differential disease progression in human immunodeficiency virus (HIV)-infected individuals, however, few class I associations with resistance or susceptibility to HIV-1 infection have been reported. We typed HLA-A, -B and -C of >1000 women enrolled in the Pumwani Sex Worker Cohort using a sequence-based typing method. Kaplan-Meier analysis was used to identify alleles influencing seroconversion and disease progression to acquired immune deficiency syndrome (CD4 < 200/mm³). A*01 (P = 0.020), C*06:02 (P = 0.042) and C*07:01 (P = 0.050) are independently associated with protection from seroconversion. Women with any of these alleles are less likely to seroconvert [P = 0.00001, odds ratio (OR): 0.503, 95% confidence interval (CI): 0.320-0.790]. Conversely, A*23:01 (P = 0.004), B*07:02 (P = 0.003) and B*42:01 (P = 0.025) are independently associated with rapid seroconversion. Women with any of these alleles are twice as likely to seroconvert (P = 0.002, OR: 2.059, 95% CI: 1.290-3.285). The beneficial alleles confer threefold protection from seroconversion when compared with the susceptible alleles (P = 0.000001, OR: 0.268, 95% CI: 0.132-0.544). B*07:02 is the contributing allele, within the B7 supertype, to the rapid seroconversion. A*74:01 (P = 0.04/P = 0.006), B*14 (P = 0.003/P = 0.003) and B*57:03 (P = 0.012/P = 0.038) are independently associated with slower CD4+ decline and LTNP phenotype, while B*07:02 (P = 0.020), B*15:10 (P = 0.022) and B*53:01 (P = 0.007) are independently associated with rapid CD4+ T-cell decline. B7 supertype (P = 0.00006), B*35*-Py (P = 0.028) and B*35-Px (P = 0.001) were also significantly associated with rapid CD4+ T-cell decline. Understanding why these HLA class I alleles are associated with protection/susceptibility to HIV-1 acquisition and disease progression could contribute to the development of effective prophylactic and therapeutic vaccines for HIV-1.

Anal and dry sex in commercial sex work, and relation to risk for sexually transmitted infections and HIV in Meru, Kenya.

OBJECTIVE: To examine the practices of anal intercourse and dry sex within a cohort of female sex workers (FSWs) in Kenya, focusing on the prevalence and perceived risk of the practices, demographic and behavioural correlates, and association with sexually transmitted infections (STI). METHODS: A survey was conducted among FSWs in Meru, Kenya, with 147 participants randomly sampled from an existing cohort of self identified FSWs. RESULTS: 40.8% of participants reported ever practising anal intercourse and 36.1% reported ever practising dry sex. Although the majority of women surveyed believed anal intercourse and dry sex to be high risk practices for HIV infection compared with vaginal sex, about one third of women reported never or rarely using condoms during anal intercourse, and about 20% never or rarely using condoms during dry sex. Reported consistent condom use was lower with both of these practices than with penile-vaginal intercourse. Anal intercourse was associated with experience of recent forced sexual intercourse, while dry sex was not. Anal intercourse was almost always initiated by clients, whereas dry sex was likely to be initiated by the women themselves. Sex workers reported charging higher fees for both practices than for vaginal intercourse. Both practices were associated with reported symptoms and diagnoses of STI. CONCLUSIONS: Both anal intercourse and dry sex were common in this sample, and although perceived as high risk practices, were not adequately protected with condom use. Education and other interventions regarding these high risk sexual behaviours need to be translated into safer practices, particularly consistent condom use, even in the face of financial vulnerability.

Sexual patterning and condom use among a group of HIV vulnerable men in Thika, Kenya.

BACKGROUND/AIM: A composite sample of 37 peer educators and 215 members of self help groups of male informal sector workers in Thika, Kenya, targeting HIV/AIDS prevention, were interviewed about their sexual behaviour, using a customised template, as part of a broader survey on gender attitudes and peer pressure. METHOD: Details on each sexual partner reported by each man over a 12 month recall period included type of partner, months during which sexual relations took place, and condom use. RESULTS: The men reported 471 sexual partners over the recall period, with a range of 0-16 partners, and an average of just under two partners. 8% of men had had no sexual partner, half were monogamous, and 3% had multiple partners with whom they used condoms exclusively, leaving 39% at varying degrees of risk. Condom use increased significantly with reduced intimacy of partner. 16% of men reported having at least one liaison with a female sex worker and two thirds of such liaisons were exclusively protected by condom use. Younger, single men had significantly more partners, but were more likely to use condoms. Duration of membership in self help groups was strongly associated with exclusive use of condoms with casual or FSW partners. Recorded attitudes corresponded somewhat with practice, but the data showed large gaps between the two, and low levels of gender sensitivity. CONCLUSION: There is some evidence that group membership has resulted in increased condom use and partner reduction, but there are doubts as to the extent to which the "ABC" strategy can be successful in stemming the HIV/AIDS epidemic. It may be necessary for interventions to target contextual issues, particularly gender relations, if the approach is to be more successful.

Decentralisation of tuberculosis treatment from the main hospitals to the peripheral health units and in the community within Machakos district, Kenya.

SETTING: A rural district, Machakos, in Kenya, facing decreasing national resources for health and an increasing tuberculosis (TB) caseload fuelled by the human immunodeficiency virus (HIV). OBJECTIVE: To evaluate the impact on district TB programme performance of decentralising TB treatment by providing ambulatory care in the hospital and peripheral health units and in the community. METHODS: A comparative study of district TB programme performance before and after the decentralisation of TB services at the end of 1997. To facilitate ambulatory care, ethambutol replaced streptomycin in the new treatment regimen. FINDINGS: The number of patients registered in the control period (1996) was 1141, of whom almost 100% were admitted during the intensive phase of TB treatment, and in the intervention period (1998 and 1999), it was 3244, of whom only 153 (4.7%) required admission in the intensive phase. Of 3244 TB patients (all forms) registered in the intervention period, the number (%) choosing the different options for directly observed treatment (DOT) supervision were: hospital clinic 1618 (49.9%), peripheral health unit 904 (27.9%), community volunteer 569 (17.5%) and hospitalisation 153 (4.7%). The options were found to be acceptable to patients, their families and health staff. The treatment outcomes among new sputum smear-positive pulmonary TB patients were similar in the intervention and control cohorts, with treatment success rates of 88% vs. 85% and death rates of 4% vs. 6%, respectively. Treatment completion was significantly higher among new sputum smear-negative and extra-pulmonary TB patients in the intervention than in the control cohort (79% vs. 48%, respectively). CONCLUSION: The decentralisation of the intensive phase of TB treatment resulted in maintenance of good TB programme performance, while Machakos hospital closed its TB wards. A separate paper describes the cost-effectiveness of this approach. The National Tuberculosis Control Programme plans to adopt this approach as national policy.

Response of a sexually transmitted infection epidemic to a treatment and prevention programme in Nairobi, Kenya.

Although it seems possible in a developing country context such as Kenya, given appropriate inputs and a sound approach, to shift a sexually transmitted disease (STI) epidemic from phase II to III, it is not entirely clear how to go beyond this stage, to low levels of endemicity or even elimination. Perhaps the most important challenge now is to expand STI treatment and community STI/HIV prevention programmes to a much larger scale. Although successful programmes have been implemented in many areas of sub-Saharan Africa on a small scale, a significant impact in reducing the STI/HIV burden will not occur until programme reach is expanded to district, provincial, and national levels.

Human leucocyte antigen supertypes and immune susceptibility to HIV-1, implications for vaccine design.

T cell responses against HIV-1 have been identified in a number of exposed uninfected populations. We hypothesized that the ability to mount an effective T cell response is partly determined by the human leucocyte antigens (HLA) phenotype of the individual. We examined whether certain HLA supertypes were associated with differential HIV-1 susceptibility in sexually exposed adults and in the setting of mother to child HIV-1 transmission. By multivariate analysis, decreased HIV-1 infection risk was strongly associated with possession of a cluster of closely related class I HLA alleles (A2/6802 supertype) in sexually exposed adults (Hazard ratio=0.42, 95% confidence intervals (CI): 0.22-0.81, P=0.009) and perinatally exposed infants (Odds ratio=0.12, 95% CI: 0.03-0.54, P=0.006). The alleles in this HLA supertype are known in some cases, to present the same peptide epitopes (termed 'supertopes'), for T cell recognition. The identification of HIV-1 supertopes, which are associated with protection from HIV-1 infection, has important implications for the application of epitope-based HIV-l vaccines in a variety of racial groups.

Evaluation of a low-dose nonoxynol-9 gel for the prevention of sexually transmitted diseases: a randomized clinical trial.

BACKGROUND: Low-dose nonoxynol-9 products have a potential advantage of reduced toxicity. However, little is known about their efficacy in reducing the incidence of sexually transmitted diseases (STDs). GOAL: To determine the effect that an intravaginal gel containing 52.5 mg of nonoxynol-9 has on the acquisition of STDs in a cohort of HIV-1-seronegative female sex workers in Mombasa, Kenya. STUDY DESIGN: A randomized double-blind placebo controlled trial was performed. RESULTS: In this study, 139 women were randomized to the nonoxynol-9 group and 139 to the placebo group. No significant differences were found between the two study groups in terms of safety outcomes and reported symptoms, except for a lower incidence of vaginal erythema in the nonoxynol-9 group. There was a significantly higher incidence of gonorrhea in the nonoxynol-9 group than in the placebo group. No significant differences were observed between the groups for acquisition of Candida, trichomonas, bacterial vaginosis, C trachomatis, syphilis, or HIV-1, although the statistical power to detect differences for some of these STDs was limited. CONCLUSIONS: In this randomized placebo-controlled trial of a low-dose nonoxynol-9 gel, a significantly higher incidence of gonorrhea was found in the nonoxynol-9 group, but no significant differences between the groups were found for Candida, trichomonas, bacterial vaginosis, C trachomatis, syphilis, or HIV-1.

Sexually transmitted infections and vaginal douching in a population of female sex workers in Nairobi, Kenya.

OBJECTIVE: To assess the association between vaginal douching and sexually transmitted infections (STI) among a group of female sex workers (FSWs) in Nairobi, Kenya. METHODS: This study was part of a randomised, placebo controlled trial of monthly prophylaxis with 1 g of azithromycin to prevent STIs and HIV infection in a cohort of Nairobi FSWs. Consenting women were administered a questionnaire and screened for STIs. RESULTS: The seroprevalence of HIV-1 among 543 FSWs screened was 30%. HIV infection was significantly associated with bacterial vaginosis (BV), trichomoniasis, gonorrhoea, and the presence of a genital ulcer. Regular douching was reported by 72% of the women, of whom the majority inserted fluids in the vagina, generally after each sexual intercourse. Water with soap was the fluid most often used (81%), followed by salty water (18%), water alone (9%), and a commercial antiseptic (5%). Douching in general and douching with soap and water were significantly associated with bacterial vaginosis (p = 0.05 and p = 0.04 respectively). There was a significant trend for increased frequency of douching and higher prevalence of BV. There was no direct relation observed between douching and risk for HIV infection or other STIs. CONCLUSION: The widespread habit of douching among African female sex workers was confirmed. The association between vaginal douching and BV is of concern, given the increased risk of HIV infection with BV, which has now been shown in several studies. It is unclear why we could not demonstrate a direct association between douching and HIV infection. Further research is required to better understand the complex relation between douching, risk for bacterial vaginosis, and risk for HIV and other STIs.

Trends in HIV-1 incidence in a cohort of prostitutes in Kenya: implications for HIV-1 vaccine efficacy trials.

BACKGROUND: Accurate predictions of HIV-1 incidence in potential study populations are essential for designing HIV-1 vaccine efficacy trials. Little information is available on the estimated incidence of HIV-1 in such populations, especially information on incidence over time and incidence while participating in risk-reduction programs. OBJECTIVES: To examine time trends in HIV-1 incidence in a vaccine preparedness cohort. DESIGN: Prospective cohort study of female prostitutes in Mombasa, Kenya. METHODS: HIV-1 incidence was determined using open and closed cohort designs. Generalized estimating equations were used to model HIV-1 and sexually transmitted disease (STD) incidence and sexual risk behaviors over time. RESULTS: When analyzed as a closed cohort, HIV-1 incidence declined 10-fold during 3 years of follow-up (from 17.4 to 1.7 cases/100 person-years; p <.001). More than 50% of the cases of HIV-1 occurred during the first 6 months after enrollment, and 73% during the first 12 months. When analyzed as an open cohort, HIV-1 incidence density fell during the first 4 calendar years, influenced by accumulation of lower risk participants and variations in study recruitment. Significant declines occurred in both STD incidence and high-risk sexual behaviors during follow-up. CONCLUSIONS: This study documents a dramatic decline in the risk of HIV-1 infection while participating in a prospective cohort, with most seroconversions occurring within 1 year of enrollment. Variations in HIV-1 incidence within high-risk populations should be anticipated during the design of vaccine trials.

Acute sexually transmitted infections increase human immunodeficiency virus type 1 plasma viremia, increase plasma type 2 cytokines, and decrease CD4 cell counts.

In Kenya, the median incubation time to AIDS in seroconverting sex workers is 4 years; this incubation time is specific to female sex workers. We studied the influence of acute sexually transmitted infections (STIs) on several immunologic parameters in 32 human immunodeficiency virus type 1 (HIV-1)-positive and 10 HIV-1-negative women sex workers who were followed for 1-5 months. Plasma cytokines, soluble cytokine receptors, CD4 and CD8 T cell counts, and HIV-1 plasma viremia were quantitated before, during, and after episodes of STI. Increases in interleukin (IL)-4, IL-6, IL-10, soluble tumor necrosis factor (TNF)-alpha, and viremia and a decline in CD4(+) T cell counts occurred during gonococcal cervicitis and returned to baseline after treatment. Increases in viremia correlated with increased IL-4 and decreased IL-6 concentrations. Similar changes were seen among women with acute pelvic inflammatory disease. Acute bacterial STI resulted in increased HIV-1 viremia. This may be mediated through increased inflammatory cytokines or through modulation of immune responses that control HIV-1 viremia.

Influence of HLA supertypes on susceptibility and resistance to human immunodeficiency virus type 1 infection.

Certain human leukocyte antigens, by presenting conserved immunogenic epitopes for T cell recognition, may, in part, account for the observed differences in human immunodeficiency virus type 1 (HIV-1) susceptibility. To determine whether HLA polymorphism influences HIV-1 susceptibility, a longitudinal cohort of highly HIV-1-exposed female sex workers based in Nairobi, Kenya, was prospectively analyzed. Decreased HIV-1 infection risk was strongly associated with possession of a cluster of closely related HLA alleles (A2/6802 supertype; incidence rate ratio [IRR], 0.45; 95% confidence interval [CI], 0.27-0.72; P=.0003). The alleles in this supertype are known in some cases to present the same peptide epitopes for T cell recognition. In addition, resistance to HIV-1 infection was independently associated with HLA DRB1*01 (IRR, 0.22; 95% CI, 0.06-0.60; P=.0003), which suggests that anti-HIV-1 class II restricted CD4 effector mechanisms may play an important role in protecting against viral challenge. These data provide further evidence that resistance to HIV-1 infection in this cohort of sex workers is immunologically mediated.

A randomized, placebo-controlled trial of monthly azithromycin prophylaxis to prevent sexually transmitted infections and HIV-1 in Kenyan sex workers: study design and baseline findings.

Our objectives were to describe the baseline findings of a trial of antibiotic prophylaxis to prevent sexually transmitted infections (STIs) and HIV-1 in a cohort of Nairobi female sex workers (FSWs). A questionnaire was administered and a medical examination was performed. HIV-negative women were randomly assigned to either one gram azithromycin or placebo monthly. Mean age of the 318 women was 32 years, mean duration of sex work 7 years and mean number of clients was 4 per day. High-risk behaviour was frequent: 14% practised anal intercourse, 23% sex during menses, and 3% used intravenous drugs. While 20% reported condom use with all clients, 37% never use condoms. However, STI prevalence was relatively low: HIV-1 27%, bacterial vaginosis 46%, Trichomonas vaginalis 13%, Neisseria gonorrhoeae 8%, Chlamydia trachomatis 7%, syphilis 6% and cervical intraepithelial neoplasia (CIN) 3%. It appears feasible to access a population of high-risk FSWs in Nairobi with prevention programmes, including a proposed trial of HIV prevention through STI chemoprophylaxis.

Stable antenatal HIV-1 seroprevalence with high population mobility and marked seroprevalence variation among sentinel sites within Nairobi, Kenya.

OBJECTIVES: To monitor and analyse trends in HIV-1 seroprevalence among antenatal women in Nairobi, Kenya. DESIGN: Six sequential surveys were carried out among antenatal clinic attenders at four Nairobi City Council health centres between November 1991 and April 1997. METHODS: A total of 6828 women attending for first antenatal clinic visit were administered a standard questionnaire to obtain demographic information and were screened for HIV-1. RESULTS: HIV-1 seroprevalence rose from 12.1% in the first survey to 16.2% in the third, completed in October 1993. No rise was observed in subsequent surveys, and seroprevalence among women under the age of 20 declined after the third survey. Significant differences in seroprevalence (P < 0.001) were observed in all survey rounds between women who reported that their province of origin was Nyanza (22.4% overall), compared with those from other provinces in western Kenya (14.1%), and the eastern group of provinces (8.9%). The rise in HIV-1 seroprevalence observed between 1991 and 1993 was almost entirely attributable to the rising seroprevalence among women from Nyanza. There were considerable differences in HIV-1 seroprevalence among the four health centres, partly accounted for by differences in the proportion of clinic attenders from different provinces of origin, which also changed significantly over time. CONCLUSIONS: HIV-1 seroprevalence has stabilized in antenatal women attending these health centres in Nairobi, and may be declining among women in the youngest age group. This may reflect stabilization of HIV-1 incidence, but further observation is required. The levels of infection among Nairobi residents reflect the evolution of the HIV epidemic in their provinces of origin, and changing client composition influences HIV-1 seroprevalence at different clinics. HIV sentinel surveillance should be carried out at multiple sites in large urban centres to monitor accurately the evolution of the HIV epidemic and the impact of control efforts in reducing transmission.