Lameck Chinula

A randomized clinical trial on the effects of progestin contraception in the genital tract of HIV-infected and uninfected women in Lilongwe Malawi: Addressing evolving research priorities.

Hormonal contraception is central in the prevention of unintended pregnancy; however there are concerns that certain methods may increase the risk of HIV acquisition and transmission. Hormonal contraceptives may modify the genital mucosa in several ways, however the mechanisms are incompletely understood. Few studies have examined genital HIV shedding prospectively before and after initiation of hormonal contraception. The effects of hormonal contraception on genital HIV shedding in the setting of antiretroviral therapy (ART) are also unknown. We designed a pilot clinical trial in which HIV-infected and uninfected women were randomized to either depot medroxyprogesterone acetate (DMPA) injectable or levonorgestrel (LNG) implant in Lilongwe, Malawi. The objectives were to: 1) assess the effect and compare the impact of type of progestin contraception (injectable versus implant) on HIV genital shedding among HIV-infected women, 2) assess the effect and compare the impact of type of progestin contraception on inflammatory/immune markers in the genital tract of both HIV-infected and uninfected women, and 3) assess the interaction of progestin contraception and ART by examining contraceptive efficacy and ART efficacy. An additional study aim was to determine the feasibility and need for a larger study of determinants of HIV transmissibility and acquisition. As injectable contraception is widely used in many parts of the world with high HIV prevalence, this study will provide important information in determining the need for and feasibility of a larger study to address these questions that can impact the lives of millions of women living with or at risk for HIV.

HIV-associated malignancies in sub-Saharan Africa: Progress, challenges, and opportunities

Purpose of review To summarize recent developments for HIV-associated malignancies (HIVAM) in low-income and middle-income countries (LMIC) with particular focus on sub-Saharan Africa (SSA). Recent findings Antiretroviral therapy (ART) scale-up is leading to epidemiologic transitions in LMIC similar to high-income countries, with aging and growth of HIV-infected populations, declining infectious deaths, increasing cancer deaths, and transitions from AIDS-defining cancers to non-AIDS defining cancers. Despite ART scale-up, the HIVAM burden remains high including an enormous AIDS-defining cancers burden in SSA. For Kaposi sarcoma, patients treated with ART and chemotherapy can experience good outcomes even in rural SSA, but Kaposi sarcoma heterogeneity remains insufficiently understood including virologic, immunologic, and inflammatory features that may be unique to LMIC. For cervical cancer, scale-up of prevention efforts including vaccination and screening is underway, with benefits already apparent despite continuing high disease burden. For non-Hodgkin lymphoma, curative treatment is possible in the ART era even in SSA, and multifaceted approaches can improve outcomes further. For many other prevalent HIVAM, care and research efforts are being established to guide treatment and prevention specifically in LMIC. Summary Sustained investment for HIVAM in LMIC can help catalyze a cancer care and research agenda that benefits HIV-positive and HIV-negative patients worldwide.

High rates of cervical cancer among HIV-infected women at a referral hospital in Malawi.

Cervical cancer is the most common cancer among women in Malawi. National guidelines recommend screening women aged 30–45 years every five years; however, no specific recommendations exist for women with HIV. We aimed to assess the frequency of high-grade dysplasia (CIN 2 or CIN3) and cervical cancer among women in central Malawi and to examine associations with CIN2+ (CIN2/3 or cancer). We extracted cervical Pap smear, biopsy, loop electrosurgical excision procedure and uterine specimen reports from a hospital pathology database from November 2012 to November 2013. We used logistic regression to estimate associations with CIN2+. We reviewed specimens from 824 women; we excluded 194 with unknown HIV status, leaving 630 in the analytic sample. Twelve percent had high-grade dysplasia and 109 women (17%) had cancer. Twenty-five percent of high-grade dysplasia cases and 35% of cancers occurred among women outside recommended screening ages. The odds of having CIN2+ were 6.55 times (95% CI 4.44-9.67) greater for HIV+ women. High-grade dysplasia and cervical cancer are very common among Malawian women, especially HIV+ women. HIV infection was strongly associated with CIN2+. Expanding screening to women not covered by current guidelines could avert a substantial proportion of cervical cancer cases in Malawi.

Discordance between self-reported contraceptive use and detection of exogenous hormones among Malawian women enrolling in a randomized clinical trial

OBJECTIVEnThe objective was to assess the extent of concordance between self-reported contraceptive use and the presence of contraceptive progestins in serum.nnnSTUDY DESIGNnWe evaluated self-reported contraceptive use by using radioimmunoassay to examine baseline serum levels of medroxyprogesterone acetate (MPA) and levonorgestrel (LNG) among 97 Malawian women enrolling in a contraceptive trial.nnnRESULTSnTwelve percent (12/97) of study participants who reported no hormonal contraceptive use in the previous 6months had either MPA or LNG detected in their serum.nnnCONCLUSIONSnThe observed discordance between self-report and detection of exogenous hormones in serum indicates that caution is warranted when drawing conclusions based on self-reported contraceptive use.

Making HPV vaccination available to girls everywhere

Cervical cancer is currently the fourth leading cause of cancer death among women worldwide, with most cases occurring in low‐ and middle‐income countries. Safe, highly effective vaccines against HPV have been on the market since 2006, yet only 6% of girls worldwide have received this life‐saving cancer prevention intervention. International organizations, including PATH, Gavi, and the pharmaceutical companies Merck and GlaxoSmithKline, have provided support to eligible low‐ and middle‐income countries to implement national HPV vaccination programs. Still, glaring disparities in the availability of national HPV vaccination programs and the coverage of the primary target population between the global north and south persist. We illustrate worldwide HPV vaccine implementation and coverage using an online data visualization, which is publicly available and can be used to gain unique insights. We also present three emerging solutions to transform future HPV vaccine delivery in low‐ and middle‐income countries: low‐cost generics, single‐dose vaccination, and co‐administration with other adolescent vaccines. By rapidly expanding access to HPV vaccination to girls everywhere, vaccine‐type HPV infections can be virtually eliminated. At high vaccination‐coverage levels, more than 80%—or approximately 230 000—of the cervical cancer deaths that occur each year can be averted.

A tailored approach to building specialized surgical oncology capacity: Early experiences and outcomes in Malawi

Objectives Cervical cancer can often be cured by surgery alone, if diagnosed and treated early. However, of the cancer patients who live in the worlds poorest countries less that 5% have access to safe, effective and timely cancer surgery. We designed a novel, competency-based curriculum to rapidly build surgical capacity for the treatment of cervical cancer. Here we report experiences and early outcomes of its implementation in Malawi. Methods Curriculum implementation consisted of preoperative evaluation of patients and surgical video review, discussion of surgical instruments and suture material, deconstruction of the surgical procedure into critical subcomponents including trainees walking through the steps of the procedure with the master trainers, high-volume surgical repetition over a short time interval, intra-operative mentoring, post-operative case review, and mental narration. This was preceded by self-directed learning and followed by clinical mentorship through electronic communication and quarterly on-site visits. Results Between June 2015–June 2017, 28 patients underwent radical abdominal hysterectomy with bilateral pelvic lymphadenectomy. The first 8 surgeries were performed over 5u202fdays. After the 7th case the trainee could perform the procedure alone. During and between quarterly mentoring-visits the trainee independently performed the procedure on 20 additional patients. Major surgical complications were rare. Conclusions Life-saving surgical treatment for cervical cancer is now available for the first time, as a routine clinical service, in Central/Northern, Malawi.

Family planning knowledge, experiences and reproductive desires among women who had experienced a poor obstetric outcome in Lilongwe Malawi: a qualitative study

BackgroundPerinatal mortality is unacceptably high in low-income countries, including Malawi. Use of family planning to encourage birth spacing may optimize outcomes for subsequent pregnancies. However, the reproductive desires and family planning knowledge of women who have experienced a stillbirth or neonatal death in resource-poor settings are not well understood.MethodsWe examined family planning knowledge, contraceptive practices and barrier to contraceptive use among women who had experienced a poor obstetric outcome at Bwaila Hospital in Lilongwe, Malawi. We performed individual in-depth interviews or through focus group discussion with women who had experienced a stillbirth or early neonatal death, 4–8xa0weeks after their delivery. NVivo software was used to analyze data for recurrent patterns and themes, and central ideas were extracted to identify the data’s core meanings.ResultsWe interviewed 46 women who had experienced a poor obstetric outcome. Overall, women were aware of both modern and traditional family planning methods, and the majority were in favour of modern versus traditional methods. They also had knowledge about risks for future complications if they have a short inter-pregnancy interval. However, they faced conflict about whether to use family planning methods for their health, as suggested by their relatives and friends, or to have another child to fulfil their husband’s desire, especially among those with no living child. Some had fear about side effects, while others were concerned that use of family planning methods without involving the husband could bring misunderstandings within the family. A number of women had misconceptions about family planning methods, which also served as a barrier to their use.ConclusionAlthough women with a poor obstetric outcome are aware of modern family planning and its health benefits after their delivery, their decision to use a method is complicated by their own desire to protect their own health and the husband’s desire for a child, particularly among those women with no living children coupled with fear of side effects and misconceptions. These findings suggest the importance of counselling both the affected woman and her husband about the benefits of family planning use, even after a poor obstetric outcome, to jointly choose the method they feel comfortable to use and dispel any misconceptions.Trial registrationClinicaltrials.gov NCT02674542.

Effect of the depot medroxyprogesterone acetate injectable and levonorgestrel implant on HIV genital shedding: a randomized trial

Objectives To assess the effect of the depot medroxyprogesterone acetate injectable (DMPA) and of the levonorgestrel (LNG) implant on genital HIV shedding among women receiving antiretroviral therapy (ART). Methods We randomized HIV-infected Malawian women to either DMPA or LNG implant from May 2014 to April 2015. HIV RNA was measured in cervicovaginal lavage (CVL) fluid and TearFlo Strips (TFS), and HIV DNA was measured in cells collected by CVL. We compared the frequency and magnitude of HIV genital shedding before and for 6u202fmonths after initiation of contraception and between arms among women receiving ART. We also compared genital HIV RNA levels obtained by sample type (TFS versus CVL). Results We analyzed data for 68 HIV-infected women receiving ART: 33 randomized to DMPA and 35 randomized to the LNG implant. Overall, HIV RNA was more often detectable and the quantity was higher on TFS compared with CVL. HIV DNA was detected very rarely in CVL cell samples (4 of 360 samples). The frequency of genital shedding and the genital HIV quantity did not increase after contraceptive initiation with either DMPA or LNG implant among women receiving ART. Conclusions HIV-infected women receiving ART initiating contraception with either DMPA or LNG implant did not have any increase in genital HIV shedding during the first 6u202fmonths of contraceptive use. These findings are consistent with growing evidence that progestin contraception is not associated with increased HIV transmission risk from such women to their male partners. Consistent with other studies, genital HIV RNA detection was higher in TFS than in CVL fluid. Implications In this randomized trial, neither DMPA nor the LNG implant, two of the most commonly used hormonal contraceptives among African women with HIV, was associated with increased genital HIV shedding in HIV-infected women receiving ART. These findings are reassuring and add to the currently limited information available for the highly effective contraceptive, LNG implant.

Influences on birth spacing intentions and desired interventions among women who have experienced a poor obstetric outcome in Lilongwe Malawi: a qualitative study

BackgroundStillbirth and neonatal mortality are very high in many low-income countries, including Malawi. Use of family planning to encourage birth spacing may optimize outcomes for subsequent pregnancies. However, reproductive desires and influences on birth spacing preferences of women who have experienced a stillbirth or neonatal death in low-resource settings are not well understood.MethodsWe conducted a qualitative study using 20 in-depth interviews and four focus group discussions with women who had experienced a stillborn baby or early neonatal death to explore attitudes surrounding birth spacing and potential interventions to promote family planning in this population. Qualitative data were analyzed for recurrent patterns and themes and central ideas were extracted to identify their core meanings.ResultsForty-six women participated in the study. After experiencing a stillbirth or neonatal death, most women wanted to wait to become pregnant again but women with living children wished to wait for longer periods of time than those with no living children. Most women preferred birth spacing interventions led by clinical providers and inclusion of their spouses.ConclusionsMany influences on family size and birth spacing were noted in this population, with the most significant influencing factor being the spouse. Interventions to promote birth spacing and improve maternal and neonatal health in this population need to involve male partners and knowledgeable health care providers to be effective.Trial registrationClinicaltrials.gov NCT02674542 Registered February 1, 2016 (retrospectively registered).

P3.242 Factors associated with vaginal prostate-specific antigen detection and self-reported unprotected sex in a clinical trial in malawi

Introduction Vaginal prostate-specific antigen (PSA) is a biomarker of recent semen exposure that may overcome potential fallacies of self-reported sexual behaviours, improving sexual exposure assessment in HIV/STI research. Methods We conducted a cohort study to compare PSA detection and self-reported unprotected sex using data from a clinical trial in Malawi that randomised 73 HIV-infected and 24 HIV-uninfected women to depot medroxyprogesterone acetate injectable or levonorgestrel implant. Women were advised to abstain from vaginal intercourse or use a condom the day preceding study visits. We tested 539 vaginal swabs from 97 women for PSA using the ABAcard p30 rapid strip test (Abacus Diagnostics, Inc., West Hills, CA). Self-reported sexual behaviours and vaginal swabs were collected at six study visits. Log-binomial regression with generalised estimating equations were used to estimate associations of PSA detection and reported unprotected sex with demographic and behavioural factors, adjusting for study arm and pre- vs. post-contraception initiation. Results Overall, 55 (57%) women tested positive for PSA and 54 (56%) women reported unprotected sex. Among PSA-positive samples, 62% (65/105) of instances reported no unprotected sex. The following were associated with PSA detection: HIV-negative status (Prevalence Ratio (PR): 1.69, 95% Confidence Interval (CI):1.09, 2.61), younger age (PR: 1.04, CI: 1.00, 1.08), reported unprotected sex (PR: 2.48, CI: 1.70, 3.60), and sex within past 48u2009hours (PR: 4.68, CI: 3.00, 7.30). The same factors were significantly associated with self-reported unprotected sex, as was PSA detection (PR: 2.45, CI: 1.7, 3.53). Conclusions Self-reported sexual behaviours were significantly associated with PSA detection. However, PSA was detected among women reporting no unprotected sex, suggesting misreporting of condom use or condom failure. HIV-negative status and younger age were associated with unprotected sex, suggesting more frequent biases in research data for these groups based on social desirability and non-adherence to protocols.